Edible Matrix Code with Photogenic Silk ProteinsClick to copy article linkArticle link copied!
- Jung Woo LeemJung Woo LeemWeldon School of Biomedical Engineering, Purdue University, West Lafayette, Indiana 47907, United StatesMore by Jung Woo Leem
- Hee-Jae JeonHee-Jae JeonWeldon School of Biomedical Engineering, Purdue University, West Lafayette, Indiana 47907, United StatesMore by Hee-Jae Jeon
- Yuhyun JiYuhyun JiWeldon School of Biomedical Engineering, Purdue University, West Lafayette, Indiana 47907, United StatesMore by Yuhyun Ji
- Sang Mok ParkSang Mok ParkWeldon School of Biomedical Engineering, Purdue University, West Lafayette, Indiana 47907, United StatesMore by Sang Mok Park
- Yunsang KwakYunsang KwakDepartment of Mechanical System Engineering, Kumoh National Institute of Technology, 61 Daehak-ro, Gumi-si, Gyeongsangbuk-do 39177, Republic of KoreaMore by Yunsang Kwak
- Jongwoo ParkJongwoo ParkDepartment of Agricultural Biology, National Institute of Agricultural Sciences, Rural Development Administration, Wanju, Jeollabuk-do 55365, Republic of KoreaMore by Jongwoo Park
- Kee-Young KimKee-Young KimDepartment of Agricultural Biology, National Institute of Agricultural Sciences, Rural Development Administration, Wanju, Jeollabuk-do 55365, Republic of KoreaMore by Kee-Young Kim
- Seong-Wan Kim*Seong-Wan Kim*Email: [email protected] (S.-W.K.).Department of Agricultural Biology, National Institute of Agricultural Sciences, Rural Development Administration, Wanju, Jeollabuk-do 55365, Republic of KoreaMore by Seong-Wan Kim
- Young L. Kim*Young L. Kim*Email: [email protected] (Y.L.K.).Weldon School of Biomedical Engineering, Purdue University, West Lafayette, Indiana 47907, United StatesPurdue University Center for Cancer Research, West Lafayette, Indiana 47907, United StatesRegenstrief Center for Healthcare Engineering, West Lafayette, Indiana 47907, United StatesPurdue Quantum Science and Engineering Institute, West Lafayette, Indiana 47907, United StatesMore by Young L. Kim
Abstract
Counterfeit medicines are a healthcare security problem, posing not only a direct threat to patient safety and public health but also causing heavy economic losses. Current anticounterfeiting methods are limited due to the toxicity of the constituent materials and the focus of secondary packaging level protections. We introduce an edible, imperceptible, and scalable matrix code of information representation and data storage for pharmaceutical products. This matrix code is digestible as it is composed of silk fibroin genetically encoded with fluorescent proteins produced by ecofriendly, sustainable silkworm farming. Three distinct fluorescence emission colors are incorporated into a multidimensional parameter space with a variable encoding capacity in a format of matrix arrays. This code is smartphone-readable to extract a digitized security key augmented by a deep neural network for overcoming fabrication imperfections and a cryptographic hash function for enhanced security. The biocompatibility, photostability, thermal stability, long-term reliability, and low bit error ratio of the code support the immediate feasibility for dosage-level anticounterfeit measures and authentication features. The edible code affixed to each medicine can serve as serialization, track and trace, and authentication at the dosage level, empowering every patient to play a role in combating illicit pharmaceuticals.
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License Summary*
You are free to share(copy and redistribute) this article in any medium or format and to adapt(remix, transform, and build upon) the material for any purpose, even commercially within the parameters below:
Creative Commons (CC): This is a Creative Commons license.
Attribution (BY): Credit must be given to the creator.
*Disclaimer
This summary highlights only some of the key features and terms of the actual license. It is not a license and has no legal value. Carefully review the actual license before using these materials.
License Summary*
You are free to share(copy and redistribute) this article in any medium or format and to adapt(remix, transform, and build upon) the material for any purpose, even commercially within the parameters below:
Creative Commons (CC): This is a Creative Commons license.
Attribution (BY): Credit must be given to the creator.
*Disclaimer
This summary highlights only some of the key features and terms of the actual license. It is not a license and has no legal value. Carefully review the actual license before using these materials.
Synopsis
An edible code affixed to each medicine offers anticounterfeit measures and authentication features at the dosage level, empowering every patient to play a role in combating illicit pharmaceuticals.
Introduction
Results and Discussion
Figure 1
Figure 1. Schematic illustration of an edible matrix code for anticounterfeiting pharmaceutical products and on-dose (or in-dose) authentication. Like other machine-readable barcodes or 2D matrix codes (e.g., QR code), the proposed code is a method of digital information representation and data storage but has unique features to be edible, imperceptible, and multidimensional, using three different fluorescent natural biopolymers (i.e., silk fibroin and fluorescent protein). After being affixed to an individual medicine by the pharmaceutical manufacturer or the hospital pharmacy, this code becomes an integrated part of the medicine. The end user or consumer (e.g., patient) can use a smartphone camera to read the code (i.e., fluorescence images). A digitized key is generated from the code by a deep neural network for quick and accurate key extraction. The extracted digital key is converted to a cryptographic hashed key through a hash function. As a result, the patient can be empowered to authenticate the medicine with the necessary dose information immediately before oral intake.
Figure 2
Figure 2. Fabrication of edible matrix codes using silk fibroin genetically hybridized with fluorescent proteins. (a) Schematic representation of transformation vector structures for silkworm transgenesis, p3×P3-DsRed2-pFibH-eCFP for eCFP silk, p3×P3-DsRed2-pFibH-eGFP for eGFP silk, and p3×P3-eGFP-pFibH-mKate2 for mKate2 silk. Fibroin heavy chain promoter domain (pFibH, 1124 base pairs (bp)), N-terminal region 1 (NTR1, 142 bp), Intron (871 bp), N-terminal region 2 (NTR2, 417 bp), C-terminal region (CTR, 179 bp), poly(A) signal region (PolyA, 301 bp), enhanced cyan fluorescent protein (eCFP, 720 bp), enhanced green fluorescent protein (eGFP, 720 bp), monomeric far-red fluorescent protein (mKate2, 699 bp), inverted repeat sequences of piggyBac arms (ITR), 3×P3 promoter (273 bp), and Sv40 polyadenylation signal sequence (Sv40pA, 268 bp). Red fluorescent protein (DsRed2) is used only for a marker gene of eCFP and eGFP, while eGFP is utilized for a marker gene of mKate2. (b) Photographs and fluorescence images of eCFP silk, eGFP silk, and mKate2 silk cocoons, compared with a nontransgenic (wild-type) white silk cocoon. Each silk fibroin solution is regenerated from the corresponding silk cocoons. (c, d) Optical absorption (c) and fluorescence emission (d) spectra of fluorescent silk fibroin films fabricated using the regenerated eCFP silk (cyan), eGFP silk (green), and mKate2 silk (red) fibroin solutions. (e) Photographs and fluorescence images of three different fluorescent silk fibroin films and a white silk fibroin film using an appropriate set of optical excitation and emission. A set of an excitation source (λex) and an emission filter (λem) is used as follows: λex = 415 nm and λem = 460 nm, λex = 470 nm and λem = 525 nm, and λex = 530 nm and λem = 630 nm for eCFP silk, eGFP silk, and mKate2 silk, respectively. The thickness of the fluorescent silk fibroin films is 70 μm on average. (f) Scanning electron microscopy images of conical micrograting arrays with 2D periodic hexagonal patterns. The height and bottom diameter of each grating are 1.4 and 2.7 μm with a distance (i.e., period) between adjacent gratings of 2.9 μm. (g) Photographs of light propagation (green laser at λ = 532 nm) through bare (top) and micrograting patterned (bottom) silk fibroin films. (h) Photograph of 7 × 7 matrix codes fabricated using bare (left) and micrograting patterned (right) silk fibroin films, affixed onto the tablet-type medicine (oral solid dosage). The code pattern on the micrograting patterned silk fibroin film is covert and imperceptible due to the strong diffraction of light caused by the micrograting arrays.
Figure 3
Figure 3. Cryptographic key generation of an edible code with three distinct fluorescence colors and digital signature generation with a hash algorithm. (a) Extraction process of digitized output keys from raw fluorescence input images of a representative edible code (7 × 7 matrix). Three different fluorescence images are acquired with an optical set of excitation and emission: eCFP silk code pattern (cyan); λex = 415 nm and λem = 460 nm, eGFP silk code pattern (green); 470 and 525 nm, and mKate2 silk code pattern (red); 530 and 630 nm. Each code pattern generates a 49-bit long binary key Kb. The binary keys of three different codes are combined to a digitized key of 147 bits (Kb1 + Kb2 + Kb3). In the case of a 7 × 7 matrix code, the nominal encoding capacity is calculated to be 2147 (≈ 1.78 × 1044). (b) Convolutional neural network (CNN) architecture for output key extraction of an edible matrix code. A 2D CNN model consists of three convolutional layers and two fully connected layers (Table S1). Batch normalization is applied to each convolutional layer for faster and more stable training. After each batch normalization, the rectified linear unit (ReLU) activation function is applied, and max-pooling is performed. (c) Hashed key generation from the extracted digitized key via a cryptographic hash algorithm (e.g., MD5). Other strong hash functions can be used including SHA-256 and SHA-512. A hashed key can be used for authentication, ensuring key integrity and securing against unauthorized modifications.
Figure 4
Figure 4. Edible code applications for authentication using a smartphone. (a, b) Simulated on-dose authentication of medicines. (a) Photograph of on-dose authentication of medicines integrated with an edible code. (b) Simulated authentication process for an oral-dosage tablet-type medicine. A custom-built mobile application (app) consists of the following steps for an end user or consumer (Movie S1): launch the customized app, scan an edible code using a set of excitation (470 nm) and emission (525 nm) optical filters (Figure S11). Then, this mobile app authenticates the scanned code and further opens the embedded hyperlink to a webpage to confirm the genuine medicine information, such as product data (e.g., dosage strength, dose frequency, cautions, and expiration date), manufacturing details (e.g., location, date, batch, and lot number), and distribution path (e.g., country, distributor, and wholesaler). (c, d) Bottle-through edible code application for in-dose authentication of high-value alcoholic spirits. (c) Photograph of simulated in-dose authentication of a Scotch whisky bottle (e.g., 80 proof whisky, 40% alcohol per volume) that contains an edible code inside. To image the edible code through the bottle, the bottle is titled facing down. (d) Simulated authentication process for an alcoholic spirit containing an edible code inside. The customized mobile app can authenticate the scanned code and further inform the genuine product information (Movie S2), such as product data (e.g., type, ingredients, alcohol concentration, and cautions), manufacturing details (e.g., location, date, and serial number), and distribution path (e.g., country, distributor, and wholesaler).
Figure 5
Figure 5. Enzymatic digestibility and biocompatibility of all protein-based matrix codes. (a) Schematic illustration of the gastrointestinal tract (the stomach and the small intestine) where pepsin and trypsin are the major proteolytic enzymes produced for denaturation and degradation of dietary proteins. (b) Photographs and fluorescence images of eGFP silk fibroin films immersed in pepsin (pH 2.2) enzyme or trypsin (pH 7.2) enzyme solutions as a function of elapsed time. For comparison, buffer solutions with the same pH values without enzymes are tested. (c) Fluorescence emission intensity of eGFP silk fibroin films immersed in the proteolytic enzyme and buffer solutions at λ = 525 nm. The fluorescence intensity is normalized by the value at 0 min. The rapid decrease in the eGFP fluorescence intensity supports the denaturation and degradation of the protein-based edible codes. The enzymatic tests were repeated four times, and the error bar is a standard deviation. (d) Red blood cell hemolysis test of different silk fibroin solutions. For comparison, 0.1% Triton X-100 and phosphate-buffered saline (PBS) without silk solutions were used as positive (hemolysis efficiency of 100%) and negative (0%) controls, respectively. Inset: representative photograph of samples using sheep erythrocytes.
Conclusion
Methods
Construction of Plasmid Vector DNA for Silkworm Transgenesis
Regeneration of Transgenic Fluorescent Silk
Fabrication of Multidimensional Fluorescent Codes
Digitized Key Extraction of an Edible Code Using Deep Neural Networks
Data Augmentation for a Training Data Set and Validation of the 2D CNN Model
Biodegradability of Fluorescent Silk Fibroin Films
Hemolysis Test of Silk Fibroin Solutions
Safety Statement
Supporting Information
The Supporting Information is available free of charge at https://pubs.acs.org/doi/10.1021/acscentsci.1c01233.
Experimental details including materials, chemicals, methods, and characterization; supplemental figures including transgenic silkworms and silk glands, fabrication procedure of edible matrix codes, optical properties of micrograting patterned silk fibroin films, edible matrix codes with different matrix sizes, photostability of fluorescent silk fibroin films under alcohol treatments, square units for constructing synthetic edible matrix codes, augmented fluorescence images of edible matrix codes (7 × 7) and binary output key extraction, cryptographic key generation of edible 5 × 5 and 9 × 9 matrix codes, possible quaternary and double binary keys, smartphone reader with optical filters, and stability of silk fibroin films immersed in high-value alcoholic spirits, and photostability, thermal stability, and long-term reliability of edible matrix codes; supplemental table including the 2D CNN model information for key extraction (PDF)
Movie S1: Simulated on-dose authentication of a solid oral-dosage form (e.g., pill, tablet, or capsule) using a smartphone (AVI)
Movie S2: Simulated in-dose authentication of a high-value alcoholic spirit using a smartphone (AVI)
Terms & Conditions
Most electronic Supporting Information files are available without a subscription to ACS Web Editions. Such files may be downloaded by article for research use (if there is a public use license linked to the relevant article, that license may permit other uses). Permission may be obtained from ACS for other uses through requests via the RightsLink permission system: http://pubs.acs.org/page/copyright/permissions.html.
Acknowledgments
This work was supported by the Cooperative Research Program for Agriculture Science & Technology Development (PJ015364) from the Rural Development Administration of the Republic of Korea, the U.S. Air Force Office of Scientific Research (FA2386-17-1-4072), the NIH Technology Accelerator Challenge from the National Institutes of Health, and the Trask Innovation Fund from Purdue University.
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- 24Tesfaye, W.; Abrha, S.; Sinnollareddy, M.; Arnold, B.; Brown, A.; Matthew, C.; Oguoma, V. M.; Peterson, G. M.; Thomas, J. How do we combat bogus medicines in the age of the COVID-19 pandemic?. Am. J. Trop. Med. Hyg. 2020, 103, 1360– 1363, DOI: 10.4269/ajtmh.20-0903Google Scholar24https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BB38fnsVCqsg%253D%253D&md5=b197c3b8b046f6b499f8dea326c1aeceHow Do We Combat Bogus Medicines in the Age of the COVID-19 Pandemic?Tesfaye Wubshet; Oguoma Victor M; Abrha Solomon; Abrha Solomon; Matthew Cynthia; Peterson Gregory M; Thomas Jackson; Sinnollareddy Mahipal; Arnold Bruce; Brown Andrew; Peterson Gregory MThe American journal of tropical medicine and hygiene (2020), 103 (4), 1360-1363 ISSN:.The COVID-19 pandemic has brought concurrent challenges. The increased incidence of fake and falsified product distribution is one of these problems with tremendous impact, especially in low- and middle-income countries. Up to a tenth of medicines including antibiotics and antimalarial drugs in the African market are considered falsified. Pandemics make this worse by creating an ecosystem of confusion, distraction, and vulnerability stemming from the pandemic as health systems become more stressed and the workload of individuals increased. These environments create opportunities for substandard and falsified medicines to be more easily introduced into the marketplace by unscrupulous operators. In this work we discuss some of the challenges with fake or falsified product distribution in the context of COVID-19 and proposed strategies to best manage this problem.
- 25Newton, P. N.; Bond, K. C.; Countries, S. COVID-19 and risks to the supply and quality of tests, drugs, and vaccines. Lancet Glob. Health 2020, 8, E754– E755, DOI: 10.1016/S2214-109X(20)30136-4Google ScholarThere is no corresponding record for this reference.
- 26Schneider, M.; Ho Tu Nam, N. Africa and counterfeit pharmaceuticals in the times of COVID-19. J. Intellect. Prop. Law Pract. 2020, 15, 417– 418, DOI: 10.1093/jiplp/jpaa073Google ScholarThere is no corresponding record for this reference.
- 27Moyle, L.; Childs, A.; Coomber, R.; Barratt, M. J. #Drugsforsale: An exploration of the use of social media and encrypted messaging apps to supply and access drugs. Int. J. Drug Policy 2019, 63, 101– 110, DOI: 10.1016/j.drugpo.2018.08.005Google Scholar27https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BB3cngtVOlsg%253D%253D&md5=2d9440eb43b8190c82fc5b50d7024e51#Drugsforsale: An exploration of the use of social media and encrypted messaging apps to supply and access drugsMoyle Leah; Childs Andrew; Coomber Ross; Barratt Monica JThe International journal on drug policy (2019), 63 (), 101-110 ISSN:.BACKGROUND: The use of new technology is frequently harnessed by drug suppliers to both increase profits and reduce risk. While a growing body of research has investigated drug sales through online pharmacies and cryptomarkets, despite growing media interest, no published research exists on how smartphone-enabled social media and messaging applications ('apps') are utilised in the drug economy. This study analyses the ways such apps (e.g. Snapchat, Instagram and WhatsApp) are utilised to supply and access drugs. METHODS: Three data collection methods were employed: an international online survey of 358 drug users that had either used or considered using apps to access drugs; 'rapid' interviews (n = 20) with a similar population; and in-depth interviews (n = 27). Key issues explored were the perceived benefits and risks associated with sourcing drugs through apps, with specific attention paid to novel supply and purchasing practices. RESULTS: Apps appear to provide a quick, convenient method for connecting buyer and seller. They were often viewed as a valuable intermediary option between cryptomarkets and street dealing, providing 'secure' features and the opportunity to preview product without the requirement for technical expertise. Apps are used in a range of novel and diverse ways, including as social networking spaces in which drugs are advertised, and as encrypted messaging services for communicating with known sellers and arranging transactions. Key anxieties related to potential for exposure to law enforcement and legitimacy of substances. CONCLUSION: Though 'social supply' through friends is still typically preferred and there is a degree of wariness toward app-mediated supply, our data indicate that apps are fast becoming a viable option for accessing drugs. Apps can provide an easily accessible platform that connects buyers with commercial drug suppliers and substances that may otherwise remain elusive. Potential harms can be reduced through the provision of information which demystify common-sense assumptions that apps are secure and that this 'visual' drug economy promotes safer purchasing practices.
- 28BeSafeRx: know your online pharmacy, U.S. Food and Drug Administration (FDA), fda.gov/drugs/quick-tips-buying-medicines-over-internet/besaferx-your-source-online-pharmacy-information (Accessed August, 2021).Google ScholarThere is no corresponding record for this reference.
- 29Alliance for Safe Online Pharmacies (ASOP) Global; buysaferx.pharmacy, www.buysaferx.pharmacy (Accessed July, 2021).Google ScholarThere is no corresponding record for this reference.
- 30Bansal, D.; Malla, S.; Gudala, K.; Tiwari, P. Anti-counterfeit technologies: A pharmaceutical industry perspective. Sci. Pharm. 2013, 81, 1– 13, DOI: 10.3797/scipharm.1202-03Google Scholar30https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXkvVOmu7k%253D&md5=ab35c6b9c117cc33fad018712ab77e05Anti-counterfeit technologies: a pharmaceutical industry perspectiveBansal, Dipika; Malla, Swathi; Gudala, Kapil; Tiwari, PramilScientia Pharmaceutica (2013), 81 (1), 1-13CODEN: SCPHA4; ISSN:0036-8709. (Oesterreichische Apotheker-Verlagsgesellschaft)A review. Growth of international free trade and inadequate drug regulation have led to the expansion of trade in counterfeit drugs worldwide. Technol. protection is seen to be the best way to avoid this problem. Different technologies came into existence like overt, covert, and track and trace technologies. This review emphasizes ideal technol. characteristics, existing anti-counterfeit technologies, and their adoption in different countries. Developed countries like the USA have implemented RFID while the European trend is towards 2D barcodes. The Indian government is getting sensitized about the extent of the problem and has formulated rules mandating barcodes. Even the pharmaceutical companies have been employing these technologies in order to detain illegitimate drugs in their supply chain.
- 31Mackey, T. K.; Nayyar, G. A review of existing and emerging digital technologies to combat the global trade in fake medicines. Expert Opin. Drug Saf. 2017, 16, 587– 602, DOI: 10.1080/14740338.2017.1313227Google Scholar31https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC1cvhvVKgsg%253D%253D&md5=8aa7a16679e89cef85ef642b849ff9bcA review of existing and emerging digital technologies to combat the global trade in fake medicinesMackey Tim K; Mackey Tim K; Nayyar Gaurvika; Mackey Tim KExpert opinion on drug safety (2017), 16 (5), 587-602 ISSN:.INTRODUCTION: The globalization of the pharmaceutical supply chain has introduced new challenges, chief among them, fighting the international criminal trade in fake medicines. As the manufacture, supply, and distribution of drugs becomes more complex, so does the need for innovative technology-based solutions to protect patients globally. Areas covered: We conducted a multidisciplinary review of the science/health, information technology, computer science, and general academic literature with the aim of identifying cutting-edge existing and emerging 'digital' solutions to combat fake medicines. Our review identified five distinct categories of technology including mobile, radio frequency identification, advanced computational methods, online verification, and blockchain technology. Expert opinion: Digital fake medicine solutions are unifying platforms that integrate different types of anti-counterfeiting technologies as complementary solutions, improve information sharing and data collection, and are designed to overcome existing barriers of adoption and implementation. Investment in this next generation technology is essential to ensure the future security and integrity of the global drug supply chain.
- 32Bakan, G.; Ayas, S.; Serhatlioglu, M.; Elbuken, C.; Dana, A. Invisible thin-film patterns with strong infrared emission as an optical security feature. Adv. Opt. Mater. 2018, 6, 1800613, DOI: 10.1002/adom.201800613Google ScholarThere is no corresponding record for this reference.
- 33Trenfield, S. J.; Xian Tan, H.; Awad, A.; Buanz, A.; Gaisford, S.; Basit, A. W.; Goyanes, A. Track-and-trace: Novel anti-counterfeit measures for 3D printed personalized drug products using smart material inks. Int. J. Pharmaceut. 2019, 567, 118443, DOI: 10.1016/j.ijpharm.2019.06.034Google ScholarThere is no corresponding record for this reference.
- 34Ludasi, K.; Jójárt-Laczkovich, O.; Sovány, T.; Hopp, B.; Smausz, T.; Andrásik, A.; Gera, T.; Kovács, Z.; Regdon, G., Jr. Anti-counterfeiting protection, personalized medicines - development of 2D identification methods using laser technology. Int. J. Pharmaceut. 2021, 605, 120793, DOI: 10.1016/j.ijpharm.2021.120793Google ScholarThere is no corresponding record for this reference.
- 35Drug Supply Chain Security Act Resources for State Officials, U.S. Food and Drug Administration (FDA), fda.gov/drugs/drug-supply-chain-security-act-dscsa/drug-supply-chain-security-act-resources-state-officials, Accessed: August 2021.Google ScholarThere is no corresponding record for this reference.
- 36MediLedger; mediledger.com (Accessed June 2021).Google ScholarThere is no corresponding record for this reference.
- 37Fei, J.; Liu, R. Drug-laden 3D biodegradable label using QR code for anti-counterfeiting of drugs. Mater. Sci. Eng. C-Mater. 2016, 63, 657– 662, DOI: 10.1016/j.msec.2016.03.004Google Scholar37https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28XkvVCjt7c%253D&md5=2c322bb3d722436c1d5b726810f2b5b4Drug-laden 3D biodegradable label using QR code for anti-counterfeiting of drugsFei, Jie; Liu, RanMaterials Science & Engineering, C: Materials for Biological Applications (2016), 63 (), 657-662CODEN: MSCEEE; ISSN:0928-4931. (Elsevier B.V.)Wiping out counterfeit drugs is a great task for public health care around the world. The boost of these drugs makes treatment to become potentially harmful or even lethal. In this paper, biodegradable drug-laden QR code label for anti-counterfeiting of drugs is proposed that can provide the non-fluorescence recognition and high capacity. It is fabricated by the laser cutting to achieve the roughness over different surface which causes the difference in the gray levels on the translucent material the QR code pattern, and the micro mold process to obtain the drug-laden biodegradable label. We screened biomaterials presenting the relevant conditions and further requirements of the package. The drug-laden microlabel is on the surface of the troches or the bottom of the capsule and can be read by a simple smartphone QR code reader application. Labeling the pill directly and decoding the information successfully means more convenient and simple operation with non-fluorescence and high capacity in contrast to the traditional methods.
- 38Edinger, M.; Bar-Shalom, D.; Sandler, N.; Rantanen, J.; Genina, N. QR encoded smart oral dosage forms by inkjet printing. Int. J. Pharmaceut. 2018, 536, 138– 145, DOI: 10.1016/j.ijpharm.2017.11.052Google ScholarThere is no corresponding record for this reference.
- 39Felicity, T. Securing each dose: Reducing falsification risk with dosage level authentication. Pharmaceut. Technol. 2021, 2021 Supplement, s29– s31Google ScholarThere is no corresponding record for this reference.
- 40Altamimi, M. J.; Greenwood, J. C.; Wolff, K.; Hogan, M. E.; Lakhani, A.; Martin, G. P.; Royall, P. G. Anti-counterfeiting DNA molecular tagging of pharmaceutical excipients: An evaluation of lactose containing tablets. Int. J. Pharmaceut. 2019, 571, 118656, DOI: 10.1016/j.ijpharm.2019.118656Google ScholarThere is no corresponding record for this reference.
- 41Ilko, D.; Steiger, C.; Keller, R.; Holzgrabe, U.; Meinel, L. Tamper-proof tablets for distinction between counterfeit and originator drugs through PEG coding. Eur. J. Pharm. Biopharm. 2016, 99, 1– 6, DOI: 10.1016/j.ejpb.2015.11.009Google Scholar41https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXhvFCqtbjM&md5=c654a60ab0504ce3536689e3340807a9Tamper-proof tablets for distinction between counterfeit and originator drugs through PEG codingIlko, David; Steiger, Christoph; Keller, Rupprecht; Holzgrabe, Ulrike; Meinel, LorenzEuropean Journal of Pharmaceutics and Biopharmaceutics (2016), 99 (), 1-6CODEN: EJPBEL; ISSN:0939-6411. (Elsevier B.V.)Counterfeit drugs are a major threat to public health. Current efforts focus on serialization of the secondary packaging which do not allow to trace the individual unit. As a proof of concept, we intended to mark each tablet for its unambiguous recognition. Spiking monodisperse PEGs into tablet coating solns. at concns. as low as 3 ppm was instrumental to "write" a code into each tablet film which was readily read upon isolation and LC-MS/MS anal. Different qualities and amts. of monodisperse polyethylene glycols can be used for coding solid drug products. The approach is limited to cases in which PEGs are not present for formulation purposes as excipients, as coding against this background was unfeasible.
- 42Felton, L. A.; Shah, P. P.; Sharp, Z.; Atudorei, V.; Timmins, G. S. Stable isotope-labeled excipients for drug product identification and counterfeit detection. Drug Dev. Ind. Pharm. 2011, 37, 88– 92, DOI: 10.3109/03639045.2010.492397Google Scholar42https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3cXhsFamu7zJ&md5=42d705c51e8adf72285feaa7839da183Stable isotope-labeled excipients for drug product identification and counterfeit detectionFelton, Linda A.; Shah, Punit P.; Sharp, Zachary; Atudorei, Viorel; Timmins, Graham S.Drug Development and Industrial Pharmacy (2011), 37 (1), 88-92CODEN: DDIPD8; ISSN:0363-9045. (Informa Healthcare)Counterfeit drug products have become a major problem worldwide and a no. of techniques to detect counterfeit products or reduce the potential for counterfeiting were investigated. This study examd. the use of stable isotope-labeled excipients in solid dosage forms as a method to identify drug products and to detect counterfeits. 2H- and 13C-glucose were used as model excipients and incorporated in wet granulated formulations at a variety of different isotopic ratios. The ratios of 2H/1H and 13C/12C in each product were then detd. by isotope ratio mass spectrometry. Results demonstrated the ability to detect the isotope-labeled glucose in both granules and tablets. It was possible to use the isotope ratios to differentiate between specific batches of granules, demonstrating the potential of this technique for in-product, batch-specific identification.
- 43Grover, W. H. Candycodes: Simple universally unique edible identifiers for confirming the authenticity of pharmaceuticals. medRxiv 2021, DOI: 10.1101/2021.07.30.21261395 .Google ScholarThere is no corresponding record for this reference.
- 44Jeon, H. J.; Leem, J. W.; Ji, Y.; Park, S. M.; Park, J.; Kim, K. Y.; Kim, S. W.; Kim, Y. L. Cyber-physical watermarking with inkjet edible bioprinting. Adv. Funct. Mater. 2022, 2112479, DOI: 10.1002/adfm.202112479Google Scholar44https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB38XisFGisrw%253D&md5=72ec37dbb25ba1b5d6ff334f10accd40Cyber-Physical Watermarking with Inkjet Edible BioprintingJeon, Hee-Jae; Leem, Jung Woo; Ji, Yuhyun; Park, Sang Mok; Park, Jongwoo; Kim, Kee-Young; Kim, Seong-Wan; Kim, Young L.Advanced Functional Materials (2022), 32 (18), 2112479CODEN: AFMDC6; ISSN:1616-301X. (Wiley-VCH Verlag GmbH & Co. KGaA)Counterfeit medicines are a fundamental healthcare problem, threatening patient safety and public health as well as causing economic damage. Online pharmacies and the ongoing pandemic have promoted medicine counterfeiting. However, the existing anticounterfeit methods are limited because of material toxicity, low security, and complicated fabrication. Here a dosage-level security method is introduced that combines digital watermarking and phys. printing at the material level. A set of requirements is designed to ensure the edibility, printability, imperceptibility, and robustness of cyber-phys. watermarking. An inkjet printer using safe food coloring is adapted to print a watermarked image on a recombinant luminescent silk protein taggant to enhance attack resistance. Machine learning of color accuracy recovers unavoidable color distortions during printing and acquisition, allowing robust smartphone readability. An edible watermarked taggant affixed to each individual medicine can offer anticounterfeit and authentication features at the dosage level, empowering every patient to aid in abating illicit medicines.
- 45Fukuoka, T.; Yamaguchi, A.; Hara, R.; Matsumoto, T.; Utsumi, Y.; Mori, Y. Application of gold nanoparticle self-assemblies to unclonable anti-counterfeiting technology. In 2015 International Conference on Electronic Packaging and Imaps All Asia Conference (ICEP-IAAC) , Piscataway, New Jersey, USA, 2015, pp 432– 435.Google ScholarThere is no corresponding record for this reference.
- 46Smith, J. D.; Reza, M. A.; Smith, N. L.; Gu, J. X.; Ibrar, M.; Crandall, D. J.; Skrabalak, S. E. Plasmonic anticounterfeit tags with high encoding capacity rapidly authenticated with deep machine learning. ACS Nano 2021, 15, 2901– 2910, DOI: 10.1021/acsnano.0c08974Google Scholar46https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3MXjsFSrur4%253D&md5=1a8b0686a503227b1d57c8ba79b4e0abPlasmonic Anticounterfeit Tags with High Encoding Capacity Rapidly Authenticated with Deep Machine LearningSmith, Joshua D.; Reza, Md Alimoor; Smith, Nathanael L.; Gu, Jianxin; Ibrar, Maha; Crandall, David J.; Skrabalak, Sara E.ACS Nano (2021), 15 (2), 2901-2910CODEN: ANCAC3; ISSN:1936-0851. (American Chemical Society)Counterfeit goods create significant economic losses and product failures in many industries. Here, we report a covert anticounterfeit platform where plasmonic nanoparticles (NPs) create phys. unclonable functions (PUFs) with high encoding capacity. By allowing anisotropic Au NPs of different sizes to deposit randomly, a diversity of surfaces can be facilely tagged with NP deposits that serve as PUFs and are analyzed using optical microscopy. High encoding capacity is engineered into the tags by the sizes of the Au NPs, which provide a range of color responses, while their anisotropy provides sensitivity to light polarization. An estd. encoding capacity of 270n is achieved, which is one of the highest reported to date. Authentication of the tags with deep machine learning allows for high accuracy and rapid matching of a tag to a specific product. Moreover, the tags contain descriptive metadata that is leveraged to match a tag to a specific lot no. (i.e., a collection of tags created in the same manner from the same formulation of anisotropic Au NPs). Overall, integration of designer plasmonic NPs with deep machine learning methods can create a rapidly authenticated anticounterfeit platform with high encoding capacity.
- 47Smith, A. F.; Skrabalak, S. E. Metal nanomaterials for optical anti-counterfeit labels. J. Mater. Chem. C 2017, 5, 3207– 3215, DOI: 10.1039/C7TC00080DGoogle Scholar47https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXksVCqsr8%253D&md5=3a74db3c36cd72e4d088f84c828006dfMetal nanomaterials for optical anti-counterfeit labelsSmith, Alison F.; Skrabalak, Sara E.Journal of Materials Chemistry C: Materials for Optical and Electronic Devices (2017), 5 (13), 3207-3215CODEN: JMCCCX; ISSN:2050-7534. (Royal Society of Chemistry)The global economic, security, and health challenges presented by counterfeit goods require new approaches toward anti-counterfeit labels. This review describes recent advances in the use of metal nanomaterials for optical anti-counterfeit labels that may offer a multiplexed approach to security tags that can be easily fabricated, offer large coding capacity, and be interrogated throughout the supply chain and by the end user. This review also critically discusses the current approach to developing continuously more complex labels and offers awareness toward the need for simple, yet unclonable, taggants.
- 48Ji, X. F.; Wu, R. T.; Long, L. L.; Ke, X. S.; Guo, C. X.; Ghang, Y. J.; Lynch, V. M.; Huang, F. H.; Sessler, J. L. Encoding, reading, and transforming information using multifluorescent supramolecular polymeric hydrogels. Adv. Mater. 2018, 30, 1705480, DOI: 10.1002/adma.201705480Google ScholarThere is no corresponding record for this reference.
- 49Li, Z. Q.; Chen, H. Z.; Li, B.; Xie, Y. M.; Gong, X. L.; Liu, X.; Li, H. R.; Zhao, Y. L. Photoresponsive luminescent polymeric hydrogels for reversible information encryption and decryption. Adv. Sci. 2019, 6, 1901529, DOI: 10.1002/advs.201901529Google Scholar49https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1MXisVWqtrjF&md5=3c34ef647f19af747f03d8c7350a9529Photoresponsive Luminescent Polymeric Hydrogels for Reversible Information Encryption and DecryptionLi, Zhiqiang; Chen, Hongzhong; Li, Bin; Xie, Yanmiao; Gong, Xiaoli; Liu, Xiao; Li, Huanrong; Zhao, YanliAdvanced Science (Weinheim, Germany) (2019), 6 (21), 1901529CODEN: ASDCCF; ISSN:2198-3844. (Wiley-VCH Verlag GmbH & Co. KGaA)Conventional luminescent information is usually visible under either ambient or UV light, hampering their potential application in smart confidential information protection. In order to address this challenge, herein, light-triggered luminescence ON-OFF switchable hybrid hydrogels are successfully constructed through in situ copolymn. of acrylamide, lanthanide complex, and diarylethene photochromic unit. The open-close behavior of the diarylethene ring in the polymer could be controlled by UV and visible light irradn., where the close form of the ring features fluorescence resonance energy transfer with the lanthanide complex. The hydrogel-based blocks with tunable emission colors are then employed to construct 3D information codes, which can be read out under a 254 nm UV lamp. The exposure to 300 nm UV light leads to the luminescence quenching of the hydrogels, thus erasing the encoded information. Under visible light (>450 nm) irradn., the luminescence is recovered to make the confidential information readable again. Thus, by simply alternating the exposure to UV and visible lights, the luminescence signals could become invisible and visible reversibly, allowing for reversible multiple information encryption and decryption.
- 50Liu, F.; Nattestad, A.; Naficy, S.; Han, R.; Casillas, G.; Angeloski, A.; Sun, X.; Huang, Z. Fluorescent carbon- and oxygen-doped hexagonal boron nitride powders as printing ink for anticounterfeit applications. Adv. Opt. Mater. 2019, 7, 1901380, DOI: 10.1002/adom.201901380Google Scholar50https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1MXhvVemsr%252FI&md5=1f383bb96e108fe31d54b5a346a15d01Fluorescent Carbon- and Oxygen-Doped Hexagonal Boron Nitride Powders as Printing Ink for Anticounterfeit ApplicationsLiu, Feng; Nattestad, Andrew; Naficy, Sina; Han, Rui; Casillas, Gilberto; Angeloski, Alexander; Sun, Xudong; Huang, ZhenguoAdvanced Optical Materials (2019), 7 (24), 1901380CODEN: AOMDAX; ISSN:2195-1071. (Wiley-VCH Verlag GmbH & Co. KGaA)Increasing demands for optical anticounterfeiting technol. require the development of versatile luminescent materials with tunable photoluminescence properties. Herein, a no. of fluorescent carbon- and oxygen-doped hexagonal boron nitride (denoted as BCNO) phosphors are found to offer a such high-tech anticounterfeiting soln. These multicolor BCNO powders, developed in a two-step process with controlled annealing and oxidn., feature rod-like particle shape, with varied luminescence properties. Studies of the optical properties of BCNO, along with other characterization, provide insight into this underexplored material. Anticounterfeiting applications are demonstrated with printed patterns which are indistinguishable to the naked eye under visible light but become highly discernible under UV irradn. The fabricated patterns are demonstrated to be both chem. stable in corrosive environments and phys. robust in mech. bending testing. These properties render BCNO as promising and versatile anticounterfeiting material a wide variety of environments.
- 51Abdollahi, A.; Roghani-Mamaqani, H.; Razavi, B.; Salami-Kalajahi, M. Photoluminescent and chromic nanomaterials for anticounterfeiting technologies: Recent advances and future challenges. ACS Nano 2020, 14, 14417– 14492, DOI: 10.1021/acsnano.0c07289Google Scholar51https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXitV2ntrrK&md5=8cc3c9b883c9888f64fdd5d9c8bd92bfPhotoluminescent and Chromic Nanomaterials for Anticounterfeiting Technologies: Recent Advances and Future ChallengesAbdollahi, Amin; Roghani-Mamaqani, Hossein; Razavi, Bahareh; Salami-Kalajahi, MehdiACS Nano (2020), 14 (11), 14417-14492CODEN: ANCAC3; ISSN:1936-0851. (American Chemical Society)A review. Counterfeiting and inverse engineering of security and confidential documents, such as banknotes, passports, national cards, certificates, and valuable products, has significantly been increased, which is a major challenge for governments, companies, and customers. From recent global reports published in 2017, the counterfeiting market was evaluated to be $107.26 billion in 2016 and forecasted to reach $206.57 billion by 2021 at a compd. annual growth rate of 14.0%. Development of anticounterfeiting and authentication technologies with multilevel securities is a powerful soln. to overcome this challenge. Stimuli-chromic (photochromic, hydrochromic, and thermochromic) and photoluminescent (fluorescent and phosphorescent) compds. are the most significant and applicable materials for development of complex anticounterfeiting inks with a high-security level and fast authentication. Highly efficient anticounterfeiting and authentication technologies have been developed to reach high security and efficiency. Applicable materials for anticounterfeiting applications are generally based on photochromic and photoluminescent compds., for which hydrochromic and thermochromic materials have extensively been used in recent decades. A wide range of materials, such as org. and inorg. metal complexes, polymer nanoparticles, quantum dots, polymer dots, carbon dots, upconverting nanoparticles, and supramol. structures, could display all of these phenomena depending on their phys. and chem. characteristics. The polymeric anticounterfeiting inks have recently received significant attention because of their high stability for printing on confidential documents. In addn., the printing technologies including hand-writing, stamping, inkjet printing, screen printing, and anticounterfeiting labels are discussed for introduction of the most efficient methods for application of different anticounterfeiting inks. This review would help scientists to design and develop the most applicable encryption, authentication, and anticounterfeiting technologies with high security, fast detection, and potential applications in security marking and information encryption on various substrates.
- 52Wang, H.; Ji, X. F.; Page, Z. A.; Sessler, J. L. Fluorescent materials-based information storage. Mater. Chem. Front. 2020, 4, 1024– 1039, DOI: 10.1039/C9QM00607AGoogle Scholar52https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1MXit1Srsb7P&md5=80572fc16763a263ce2f370cbbaf7243Fluorescent materials-based information storageWang, Hu; Ji, Xiaofan; Page, Zachariah A.; Sessler, Jonathan L.Materials Chemistry Frontiers (2020), 4 (4), 1024-1039CODEN: MCFAC5; ISSN:2052-1537. (Royal Society of Chemistry)The third industrial revolution has brought mankind into the information age. The development of information storage materials has played a key role in this transformation. Such materials have seen use in many application areas, including computing, logistics, and medicine. Information storage materials run the gamut from magnetic information storage media to mol.-based information storage materials. Among these, fluorescent-based information storage materials are of particular interest due to their unique properties, including an ability to store information with high levels of security, maintain mech. stability, and respond to appropriately chosen external stimuli. In this review, we focus on recent advances involving the prepn. and study of fluorescent materials-based information storage codes. For organisational purposes, these codes are treated according to the dimensionality of the code system in question, namely 1D-, 2D-, and 3D-type codes. The present review is designed to provide a succinct summary of what has been accomplished in the area, while outlining existing challenges and noting directions for future development.
- 53Zhuang, Y. L.; Ren, X. L.; Che, X. T.; Liu, S. J.; Huang, W.; Zhao, Q. Organic photoresponsive materials for information storage: A review. Adv. Photonics 2021, 3, 014001, DOI: 10.1117/1.AP.3.1.014001Google ScholarThere is no corresponding record for this reference.
- 54Tan, J.; Li, Q. J.; Meng, S.; Li, Y. C.; Yang, J.; Ye, Y. X.; Tang, Z. K.; Qu, S. N.; Ren, X. D. Time-dependent phosphorescence colors from carbon dots for advanced dynamic information encryption. Adv. Mater. 2021, 33, 2006781, DOI: 10.1002/adma.202006781Google Scholar54https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3MXmsVCrsLo%253D&md5=a27618fcd63a17eb22dbc79f810dc7c3Time-Dependent Phosphorescence Colors from Carbon Dots for Advanced Dynamic Information EncryptionTan, Jing; Li, Qijun; Meng, Shuai; Li, Yuchen; Yang, Jian; Ye, Yunxia; Tang, Zikang; Qu, Songnan; Ren, XudongAdvanced Materials (Weinheim, Germany) (2021), 33 (16), 2006781CODEN: ADVMEW; ISSN:0935-9648. (Wiley-VCH Verlag GmbH & Co. KGaA)The development of phosphorescent materials with time-dependent phosphorescence colors (TDPCs) is of considerable interest for application in advanced dynamic information encryption. In this study, TDPC is realized in carbon dots (CDs) synthesized by the one-pot hydrothermal treatment of levofloxacin. CD ink printed on paper (CD@paper) exhibits a change in phosphorescence color from orange to green, 1 s after irradn. with 395 nm light. However, when irradiated with wavelengths shorter or longer than 395 nm, the CD@paper exhibits only green or red phosphorescence, resp. The red and green phosphorescence originates from the low-energy surface oxide triplet state and high-energy N-related triplet state, resp. When irradiated with a suitable light energy (around 395 nm wavelength), the two phosphorescent centers can be simultaneously activated, emitting red and green phosphorescence with different decay rates. The red and green phosphorescence merge into an orange phosphorescence initially, exhibiting the TDPC phenomenon. Based on the unusual phosphorescent properties of the CDs, a kind of multilevel, dynamic phosphorescence colored 3D code is designed for advanced dynamic information encryption.
- 55Yang, Y. B.; Li, Q. Y.; Zhang, H. W.; Liu, H.; Ji, X. F.; Tang, B. Z. Codes in code: Aie supramolecular adhesive hydrogels store huge amounts of information. Adv. Mater. 2021, 33, 2105418, DOI: 10.1002/adma.202105418Google Scholar55https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3MXitFagsbzO&md5=68dc444bf66d5293101d416450f0e93fCodes in Code: AIE supramolecular adhesive hydrogels store huge amounts of informationYang, Yabi; Li, Qingyun; Zhang, Hanwei; Liu, Hui; Ji, Xiaofan; Tang, Ben ZhongAdvanced Materials (Weinheim, Germany) (2021), 33 (45), 2105418CODEN: ADVMEW; ISSN:0935-9648. (Wiley-VCH Verlag GmbH & Co. KGaA)With the continuous advancement of information technol., the requirements for the information storage capacity of materials are getting higher and higher. However, information code materials usually only store a single piece of information. In order to improve their storage capacity, aggregation-induced emission (AIE) supramol. adhesive hydrogels with different fluorescent colors are prepd., and a "Codes in Code" method is used to demonstrate the storage capacity for large amts. of information. Four kinds of poly(vinyl alc.) (PVA) supramol. hydrogels with different fluorescent colors are prepd.; based on the hydrogen bonds on the hydrogel surface, these hydrogels can be assembled into a hydrogel, G5, which shows multiple fluorescent colors under the irradn. of UV light. When many 1D barcode patterns or/and 2D code patterns are incorporated into G5, not only a kind of 3D information but also plenty of 1D or/and 2D information can be stored. Therefore, the information codes prepd. by the "Codes in Code" method can store a large amt. of information.
- 56Li, Z. Q.; Liu, X.; Wang, G. N.; Li, B.; Chen, H. Z.; Li, H. R.; Zhao, Y. L. Photoresponsive supramolecular coordination polyelectrolyte as smart anticounterfeiting inks. Nat. Commun. 2021, 12, 1363, DOI: 10.1038/s41467-021-21677-4Google Scholar56https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3MXltl2gtLc%253D&md5=ddf344ad755b81b89370a68c2e090a2cPhotoresponsive supramolecular coordination polyelectrolyte as smart anticounterfeiting inksLi, Zhiqiang; Liu, Xiao; Wang, Guannan; Li, Bin; Chen, Hongzhong; Li, Huanrong; Zhao, YanliNature Communications (2021), 12 (1), 1363CODEN: NCAOBW; ISSN:2041-1723. (Nature Research)While photoluminescence printing is a widely applied anticounterfeiting technique, there are still challenges in developing new generation anticounterfeiting materials with high security. Here we report the construction of a photoresponsive supramol. coordination polyelectrolyte (SCP) through hierarchical self-assembly of lanthanide ion, bis-ligand and diarylethene unit, driven by metal-ligand coordination and ionic interaction. Owing to the conformation-dependent photochromic fluorescence resonance energy transfer between the lanthanide donor and diarylethene acceptor, the ring-closure/ring-opening isomerization of the diarylethene unit leads to a photoreversible luminescence on/off switch in the SCP. The SCP is then utilized as security ink to print various patterns, through which photoreversible multiple information patterns with visible/invisible transformations are realized by simply alternating the irradn. with UV and visible light. This work demonstrates the possibility of developing a new class of smart anticounterfeiting materials, which could be operated in a noninvasive manner with a higher level of security.
- 57Zhang, H. W.; Li, Q. Y.; Yang, Y. B.; Ji, X. F.; Sessler, J. L. Unlocking chemically encrypted information using three types of external stimuli. J. Am. Chem. Soc. 2021, 143, 18635– 18642, DOI: 10.1021/jacs.1c08558Google Scholar57https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3MXitlCrtb3L&md5=5d580be4c3c406431b020b6a9aa98f0bUnlocking Chemically Encrypted Information columnarUsing Three Types of External StimuliZhang, Hanwei; Li, Qingyun; Yang, Yabi; Ji, Xiaofan; Sessler, Jonathan L.Journal of the American Chemical Society (2021), 143 (44), 18635-18642CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)Encryption is crit. to information security; however, existing chem.-based information encryption strategies are still in their infancy. We report here a new approach to chem. encryption involving a supramol. gel QR (quick response) code with multiple encryption functions. Three color "turn-on" supramol. polymer gels, G1-G3, were prepd. that produce pink, purple, and yellow colors when subject to treatment with acetic acid vapor, UV light, and methanolic FeCl3, resp. As the result of hydrogen-bonding interactions at the gel interfaces, the three gels can be assembled to produce gel G4. Engraving a QR code pattern onto G4 then gave gel G5. When one or two stimuli are applied to the individual pieces corresponding to the QR engraved versions of the gels G1-G3 making up G5, a complete scannable pattern is not displayed, and the stored information cannot be recognized. Only when three different stimuli are applied at the same time does G5 give a complete recognizable pattern allowing the stored information to be retrieved. This strategy was applied to the decryption-based opening of a coded lock.
- 58Zhang, H. Y.; Hua, D. W.; Huang, C. B.; Samal, S. K.; Xiong, R. H.; Sauvage, F.; Braeckmans, K.; Remaut, K.; De Smedt, S. C. Materials and technologies to combat counterfeiting of pharmaceuticals: Current and future problem tackling. Adv. Mater. 2020, 32, 1905486, DOI: 10.1002/adma.201905486Google Scholar58https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXitFCiurg%253D&md5=9b0dd4aa31d6e0c1630e8e9678330c14Materials and technologies to combat counterfeiting of pharmaceuticals: Current and future problem tacklingZhang, Heyang; Hua, Dawei; Huang, Chaobo; Samal, Sangram Keshari; Xiong, Ranhua; Sauvage, Felix; Braeckmans, Kevin; Remaut, Katrien; De Smedt, Stefaan C.Advanced Materials (Weinheim, Germany) (2020), 32 (11), 1905486CODEN: ADVMEW; ISSN:0935-9648. (Wiley-VCH Verlag GmbH & Co. KGaA)A review. The globalization of drug trade leads to the expansion of pharmaceutical counterfeiting. The immense threat of low quality drugs to millions of patients is considered to be an under-addressed global health challenge. Anal. authentication technologies are the most effective methods to identify active pharmaceutical ingredients and impurities. However, most of these anal. testing techniques are expensive and need skilled personnel. To combat counterfeiting of drugs, the package of an increasing no. of drugs is being protected through advanced package labeling technologies. Though, package labeling is only effective if the drugs are not repackaged. Therefore "in-drug labeling," instead of "drug package labeling," may become powerful tools to protect drugs. This review aims to overview how advanced micro- and nanomaterials might become interesting markers for the labeling of tablets and capsules. Clearly, how well such identifiers can be integrated into "solid drugs" without compromising drug safety and efficacy remains a challenge. Also, incorporation of tags has so far only been reported for the protection of solid drug dosage forms. No doubts that in-drug labeling technologies for "liq. drugs," like injectables which contain expensive peptides, monoclonal antibodies, vaccines, dermal fillers, could help to protect them from counterfeiting as well.
- 59Huang, C. B.; Lucas, B.; Vervaet, C.; Braeckmans, K.; Van Calenbergh, S.; Karalic, I.; Vandewoestyne, M.; Deforce, D.; Demeester, J.; De Smedt, S. C. Unbreakable codes in electrospun fibers: Digitally encoded polymers to stop medicine counterfeiting. Adv. Mater. 2010, 22, 2657– 2661, DOI: 10.1002/adma.201000130Google Scholar59https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3cXosVGht7o%253D&md5=139ae432193b9e2df317489f6e307007Unbreakable Codes in Electrospun Fibers: Digitally Encoded Polymers to Stop Medicine CounterfeitingHuang, Chaobo; Lucas, Bart; Vervaet, Chris; Braeckmans, Kevin; Van Calenbergh, Serge; Karalic, Izet; Vandewoestyne, Mado; Deforce, Dieter; Demeester, Jo; De Smedt, Stefaan C.Advanced Materials (Weinheim, Germany) (2010), 22 (24), 2657-2662CODEN: ADVMEW; ISSN:0935-9648. (Wiley-VCH Verlag GmbH & Co. KGaA)A review. Health organizations claim that there should be "zero tolerance" for counterfeit medicines, yet the problem is growing world-wide. Labeling the tablet itself("one-dose marking"), instead of package labeling, could be a powerful strategy to protect patients from fake drugs. Unfortunately this methods are not in use today. This report proposes viable soln.: digitally encode polymers, which already form a major class of pharmaceutical excipients, and place them within tablets.
- 60Han, S.; Bae, H. J.; Kim, J.; Shin, S.; Choi, S. E.; Lee, S. H.; Kwon, S.; Park, W. Lithographically encoded polymer microtaggant using high-capacity and error-correctable QR code for anti-counterfeiting of drugs. Adv. Mater. 2012, 24, 5924– 5929, DOI: 10.1002/adma.201201486Google Scholar60https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC38Xht1Kitb%252FK&md5=da9342e6c8a31308910e9595c3e62e6fLithographically Encoded Polymer Microtaggant Using High-Capacity and Error-Correctable QR Code for Anti-Counterfeiting of DrugsHan, Sangkwon; Bae, Hyung Jong; Kim, Junhoi; Shin, Sunghwan; Choi, Sung-Eun; Lee, Sung Hoon; Kwon, Sunghoon; Park, WookAdvanced Materials (Weinheim, Germany) (2012), 24 (44), 5924-5929CODEN: ADVMEW; ISSN:0935-9648. (Wiley-VCH Verlag GmbH & Co. KGaA)Recently, the incorporation of microtaggants i n drug formulation has been introduced as superior on dose authentication technol. for the anticounterfeiting of drugs. Storing information or data on the microtaggant provides the multifunctionality needed for the identification and track-and-trace monitoring of drugs. Here, we propose a Quick Response (QR)-coded microtaggant that allows the encoding of a large amt. of data that will not be lost during the drug formulation process. In this work, QR-coded polymeric microtaggants were fabricated lithog. through a single exposure to QR Code-patterned UV light in the microfluidic channel. These microtaggants offer all t h e unique features of QR Code, such as highcapacity encoding, error correction capability, and omnidirectional reading. We also demonstrated the complete process of drug authentication using QR-coded microtaggants, from the formulation of the microtaggant-equipped capsule to the decoding step using a QR Code reader application on a smartphone.
- 61You, M. L.; Lin, M.; Wang, S. R.; Wang, X. M.; Zhang, G.; Hong, Y.; Dong, Y. Q.; Jin, G. R.; Xu, F. Three-dimensional quick response code based on inkjet printing of upconversion fluorescent nanoparticles for drug anti-counterfeiting. Nanoscale 2016, 8, 10096– 10104, DOI: 10.1039/C6NR01353HGoogle Scholar61https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28Xms1Wgsbo%253D&md5=7b434397603f5efaf4de57264c245433Three-dimensional quick response code based on inkjet printing of upconversion fluorescent nanoparticles for drug anti-counterfeitingYou, Minli; Lin, Min; Wang, Shurui; Wang, Xuemin; Zhang, Ge; Hong, Yuan; Dong, Yuqing; Jin, Guorui; Xu, FengNanoscale (2016), 8 (19), 10096-10104CODEN: NANOHL; ISSN:2040-3372. (Royal Society of Chemistry)Medicine counterfeiting is a serious issue worldwide, involving potentially devastating health repercussions. Advanced anti-counterfeit technol. for drugs has therefore aroused intensive interest. However, existing anti-counterfeit technologies are assocd. with drawbacks such as the high cost, complex fabrication process, sophisticated operation and incapability in authenticating drug ingredients. In this contribution, we developed a smart phone recognition based upconversion fluorescent three-dimensional (3D) quick response (QR) code for tracking and anti-counterfeiting of drugs. We firstly formulated three colored inks incorporating upconversion nanoparticles with RGB (i.e., red, green and blue) emission colors. Using a modified inkjet printer, we printed a series of colors by precisely regulating the overlap of these three inks. Meanwhile, we developed a multilayer printing and splitting technol., which significantly increases the information storage capacity per unit area. As an example, we directly printed the upconversion fluorescent 3D QR code on the surface of drug capsules. The 3D QR code consisted of three different color layers with each layer encoded by information of different aspects of the drug. A smart phone APP was designed to decode the multicolor 3D QR code, providing the authenticity and related information of drugs. The developed technol. possesses merits in terms of low cost, ease of operation, high throughput and high information capacity, thus holds great potential for drug anti-counterfeiting.
- 62Rehor, I.; van Vreeswijk, S.; Vermonden, T.; Hennink, W. E.; Kegel, W. K.; Eral, H. B. Biodegradable microparticles for simultaneous detection of counterfeit and deteriorated edible products. Small 2017, 13, 1701804, DOI: 10.1002/smll.201701804Google ScholarThere is no corresponding record for this reference.
- 63Liu, R. R.; Jing, J. B.; Zhang, S.; Wang, K.; Xu, B.; Tian, W. J.; Yang, P. Aggregation-induced emission of a 2d protein supramolecular nanofilm with emergent functions. Mater. Chem. Front. 2020, 4, 1256– 1267, DOI: 10.1039/D0QM00031KGoogle Scholar63https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXktVKitrY%253D&md5=9d136d27e94e1f899693ea4289c6007dAggregation-induced emission of a 2D protein supramolecular nanofilm with emergent functionsLiu, Ruirui; Jing, Jiangbo; Zhang, Song; Wang, Ke; Xu, Bin; Tian, Wenjing; Yang, PengMaterials Chemistry Frontiers (2020), 4 (4), 1256-1267CODEN: MCFAC5; ISSN:2052-1537. (Royal Society of Chemistry)Aggregation-induced emission (AIE) of a 2D protein supramol. nanofilm exhibiting multiple functions is achieved for the first time at the air/water interface or on a solid surface at a timescale of several minutes. The mixt. of lysozyme, tris(2-carboxyethyl)phosphine (TCEP) and 9,10-distyrylanthracene with two ammonium groups (DSAI) results in the rapid synthesis of a phase-transited lysozyme (PTL) AIE nanofilm, coating or ink from a neutral aq. soln. at room temp. The multifunctionality of these waterborne biocompatible DSAI@PTL AIE materials shows some potential applications such as anti-bacterial and anti-counterfeiting for edible items or living creatures. This strategy combines the advantages of AIE with a 2D biopolymer suprastructure and provides an eco-friendly interfacial material with biol. functions and applications. By introducing versatile AIE mols. with different functions and emission, the development of optically active biomimic materials with a wide range of applications could be opened up, such as multi-color polymer coatings.
- 64De Jong, W. H.; Borm, P. J. A. Drug delivery and nanoparticles: Applications and hazards. Int. J. Nanomed. 2008, 3, 133– 149, DOI: 10.2147/IJN.S596Google Scholar64https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1cXps1Wjt7w%253D&md5=db515c60ea3c5b6596b8802e82594c34Drug delivery and nanoparticles: applications and hazardsDe Jong, Wim H.; Borm, Paul J. A.International Journal of Nanomedicine (2008), 3 (2), 133-149CODEN: IJNNHQ; ISSN:1176-9114. (Dove Medical Press (NZ) Ltd.)A review. The use of nanotechnol. in medicine and more specifically drug delivery is set to spread rapidly. Currently many substances are under investigation for drug delivery and more specifically for cancer therapy. Interestingly pharmaceutical sciences are using nanoparticles to reduce toxicity and side effects of drugs and up to recently did not realize that carrier systems themselves may impose risks to the patient. The kind of hazards that are introduced by using nanoparticles for drug delivery are beyond that posed by conventional hazards imposed by chems. in classical delivery matrixes. For nanoparticles the knowledge on particle toxicity as obtained in inhalation toxicity shows the way how to investigate the potential hazards of nanoparticles. The toxicol. of particulate matter differs from toxicol. of substances as the composing chem.(s) may or may not be sol. in biol. matrixes, thus influencing greatly the potential exposure of various internal organs. This may vary from a rather high local exposure in the lungs and a low or neglectable exposure for other organ systems after inhalation. However, absorbed species may also influence the potential toxicity of the inhaled particles. For nanoparticles the situation is different as their size opens the potential for crossing the various biol. barriers within the body. From a pos. viewpoint, esp. the potential to cross the blood brain barrier may open new ways for drug delivery into the brain. In addn., the nanosize also allows for access into the cell and various cellular compartments including the nucleus. A multitude of substances are currently under investigation for the prepn. of nanoparticles for drug delivery, varying from biol. substances like albumin, gelatine and phospholipids for liposomes, and more substances of a chem. nature like various polymers and solid metal contg. nanoparticles. It is obvious that the potential interaction with tissues and cells, and the potential toxicity, greatly depends on the actual compn. of the nanoparticle formulation. This paper provides an overview on some of the currently used systems for drug delivery. Besides the potential beneficial use also attention is drawn to the questions how we should proceed with the safety evaluation of the nanoparticle formulations for drug delivery. For such testing the lessons learned from particle toxicity as applied in inhalation toxicol. may be of use. Although for pharmaceutical use the current requirements seem to be adequate to detect most of the adverse effects of nanoparticle formulations, it can not be expected that all aspects of nanoparticle toxicol. will be detected. So, probably addnl. more specific testing would be needed.
- 65Kumar, A.; Dhawan, A. Genotoxic and carcinogenic potential of engineered nanoparticles: An update. Arch. Toxicol. 2013, 87, 1883– 1900, DOI: 10.1007/s00204-013-1128-zGoogle Scholar65https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXhsFSkur%252FJ&md5=38e02c03bb62d2efc611d8bbcc35f174Genotoxic and carcinogenic potential of engineered nanoparticles: an updateKumar, Ashutosh; Dhawan, AlokArchives of Toxicology (2013), 87 (11), 1883-1900CODEN: ARTODN; ISSN:0340-5761. (Springer)A review. Nanoscience and nanotechnol. have seen an exponential growth over the past decade largely due to the unique properties of engineered nanoparticles (ENPs), advances in ENP synthesis, and imaging or anal. tools. The unique properties such as high surface area to vol. ratio, abundant reactive sites on the surface, large fraction of atoms located on the exterior face have made these novel materials the most sought after for consumer and industrial applications. This significant increase in the ENP contg. consumer products has also enhanced the chances of human and environmental exposure. Humans get exposed to ENPs at various steps of its synthesis (lab.), manuf. (industry), use (consumer products, devices, medicines, etc.) and through the environment (contaminated water, aerosolized particles, and disposal). Such exposures to ENPs are known to induce genotoxicity, cytotoxicity, and carcinogenicity in biol. system. This is attributed to several factors, such as direct interaction of ENPs with the genetic material, indirect damage due to reactive oxygen species generation, release of toxic ions from sol. ENPs, interaction with cytoplasmic/nuclear proteins, binding with mitotic spindle or its components, increased oxidative stress, disturbance of cell cycle checkpoint functions, inhibition of antioxidant defense, and many others. The present review describes an overview of in vitro and in vivo genotoxicity studies with ENPs, advantages and potential problems assocd. with the methods used in genotoxicity assessment, and the need for appropriate method and approach for risk assessment of ENPs.
- 66Trasande, L.; Liu, B. Y.; Bao, W. Phthalates and attributable mortality: A population-based longitudinal cohort study and cost analysis. Environ. Pollut. 2022, 292, 118021, DOI: 10.1016/j.envpol.2021.118021Google Scholar66https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3MXit1alu7bO&md5=743d42a2fb25ffb4577b064458cb0169Phthalates and attributable mortality: A population-based longitudinal cohort study and cost analysisTrasande, Leonardo; Liu, Buyun; Bao, WeiEnvironmental Pollution (Oxford, United Kingdom) (2022), 292 (Part_A), 118021CODEN: ENPOEK; ISSN:0269-7491. (Elsevier Ltd.)Accelerating evidence of endocrine-related morbidity has raised alarm about the ubiquitous use of phthalates in the human environment, but studies have not directly evaluated mortality in relation to these exposures. To evaluate assocns. of phthalate exposure with mortality, and quantify attributable mortality and lost economic productivity in 2013-4 among 55-64 yr olds. This nationally representative cohort study included 5303 adults aged 20 years or older who participated in the US National Health and Nutrition Examn. Survey 2001-2010 and provided urine samples for phthalate metabolite measurements. Participants were linked to mortality data from survey date through Dec. 31, 2015. Data analyses were conducted in July 2020. Mortality from all causes, cardiovascular disease, and cancer. Multivariable models identified increased mortality in relation to high-mol. wt. (HMW) phthalate metabolites, esp. those of di-2-ethylhexylphthalate (DEHP). Hazard ratios (HR) for continuous HMW and DEHP metabolites were 1.14 (95% CI 1.06-1.23) and 1.10 (95% CI 1.03-1.19), resp., with consistently higher mortality in the third tertile (1.48, 95% CI 1.19-1.86; and 1.42, 95% CI 1.13-1.78). Cardiovascular mortality was significantly increased in relation to a prominent DEHP metabolite, mono-(2-ethyl-5-oxohexyl)phthalate. Extrapolating to the population of 55-64 yr old Americans, we identified 90,761-107,283 attributable deaths and $39.9-47.1 billion in lost economic productivity. In a nationally representative sample, phthalate exposures were assocd. with all-cause and cardiovascular mortality, with societal costs approximating $39 billion/yr or more. While further studies are needed to corroborate observations and identify mechanisms, regulatory action is urgently needed.
- 67Davison, M. Pharmaceutical Anti-Counterfeiting: Combating the Real Danger from Fake Drugs; John Wiley & Sons, Inc.: Hoboken, NJ, USA, 2011.Google ScholarThere is no corresponding record for this reference.
- 68Ishiyama, R.; Takahashi, T.; Makino, K.; Kudo, Y.; Kooper, M.; Abbink, D., Medicine Tablet Authentication Using “Fingerprints” of Ink-Jet Printed Characters. In 2019 IEEE International Conference on Industrial Technology (ICIT); IEEE, 2019, 871– 876.Google ScholarThere is no corresponding record for this reference.
- 69Leem, J. W.; Kim, M. S.; Choi, S. H.; Kim, S. R.; Kim, S. W.; Song, Y. M.; Young, R. J.; Kim, Y. L. Edible unclonable functions. Nat. Commun. 2020, 11, 328, DOI: 10.1038/s41467-019-14066-5Google Scholar69https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXivFOgtL8%253D&md5=c0e5a56f89d170f18f3648f07fa38be3Edible unclonable functionsLeem, Jung Woo; Kim, Min Seok; Choi, Seung Ho; Kim, Seong-Ryul; Kim, Seong-Wan; Song, Young Min; Young, Robert J.; Kim, Young L.Nature Communications (2020), 11 (1), 328CODEN: NCAOBW; ISSN:2041-1723. (Nature Research)Abstr.: Counterfeit medicines are a fundamental security problem. Counterfeiting medication poses a tremendous threat to patient safety, public health, and the economy in developed and less developed countries. Current solns. are often vulnerable due to the limited security levels. We propose that the highest protection against counterfeit medicines would be a combination of a phys. unclonable function (PUF) with on-dose authentication. A PUF can provide a digital fingerprint with multiple pairs of input challenges and output responses. On-dose authentication can verify every individual pill without removing the identification tag. Here, we report on-dose PUFs that can be directly attached onto the surface of medicines, be swallowed, and digested. Fluorescent proteins and silk proteins serve as edible photonic biomaterials and the photoluminescent properties provide parametric support of challenge-response pairs. Such edible cryptog. primitives can play an important role in pharmaceutical anti-counterfeiting and other security applications requiring immediate destruction or vanishing features.
- 70Altman, G. H.; Diaz, F.; Jakuba, C.; Calabro, T.; Horan, R. L.; Chen, J. S.; Lu, H.; Richmond, J.; Kaplan, D. L. Silk-based biomaterials. Biomaterials 2003, 24, 401– 416, DOI: 10.1016/S0142-9612(02)00353-8Google Scholar70https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BD38nmtlGitg%253D%253D&md5=d66d6bd20f249166630505d09650a120Silk-based biomaterialsAltman Gregory H; Diaz Frank; Jakuba Caroline; Calabro Tara; Horan Rebecca L; Chen Jingsong; Lu Helen; Richmond John; Kaplan David LBiomaterials (2003), 24 (3), 401-16 ISSN:0142-9612.Silk from the silkworm, Bombyx mori, has been used as biomedical suture material for centuries. The unique mechanical properties of these fibers provided important clinical repair options for many applications. During the past 20 years, some biocompatibility problems have been reported for silkworm silk; however, contamination from residual sericin (glue-like proteins) was the likely cause. More recent studies with well-defined silkworm silk fibers and films suggest that the core silk fibroin fibers exhibit comparable biocompatibility in vitro and in vivo with other commonly used biomaterials such as polylactic acid and collagen. Furthermore, the unique mechanical properties of the silk fibers, the diversity of side chain chemistries for 'decoration' with growth and adhesion factors, and the ability to genetically tailor the protein provide additional rationale for the exploration of this family of fibrous proteins for biomaterial applications. For example, in designing scaffolds for tissue engineering these properties are particularly relevant and recent results with bone and ligament formation in vitro support the potential role for this biomaterial in future applications. To date, studies with silks to address biomaterial and matrix scaffold needs have focused on silkworm silk. With the diversity of silk-like fibrous proteins from spiders and insects, a range of native or bioengineered variants can be expected for application to a diverse set of clinical needs.
- 71Cao, Y.; Wang, B. C. Biodegradation of silk biomaterials. Int. J. Mol. Sci. 2009, 10, 1514– 1524, DOI: 10.3390/ijms10041514Google Scholar71https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1MXltFaisLg%253D&md5=8352d1fb9cd5bca578b73612bb06d6d5Biodegradation of silk biomaterialsCao, Yang; Wang, BochuInternational Journal of Molecular Sciences (2009), 10 (4), 1514-1524CODEN: IJMCFK; ISSN:1422-0067. (Molecular Diversity Preservation International)A review. Silk fibroin from the silkworm, Bombyx mori, has excellent properties such as biocompatibility, biodegrdn., non-toxicity, adsorption properties, etc. As a kind of ideal biomaterial, silk fibroin has been widely used since it was first utilized for sutures a long time ago. The degrdn. behavior of silk biomaterials is obviously important for medical applications. This article will focus on silk-based biomaterials and review the degrdn. behaviors of silk materials.
- 72Thurber, A. E.; Omenetto, F. G.; Kaplan, D. L. In vivo bioresponses to silk proteins. Biomaterials 2015, 71, 145– 157, DOI: 10.1016/j.biomaterials.2015.08.039Google Scholar72https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXhtlOgsbjP&md5=0132b88fc83433397da2ced631b6b707In vivo bioresponses to silk proteinsThurber, Amy E.; Omenetto, Fiorenzo G.; Kaplan, David L.Biomaterials (2015), 71 (), 145-157CODEN: BIMADU; ISSN:0142-9612. (Elsevier Ltd.)Silks are appealing materials for numerous biomedical applications involving drug delivery, tissue engineering, or implantable devices, because of their tunable mech. properties and wide range of phys. structures. In addn. to the functionalities needed for specific clin. applications, a key factor necessary for clin. success for any implanted material is appropriate interactions with the body in vivo. This review summarizes our current understanding of the in vivo biol. responses to silks, including degrdn., the immune and inflammatory response, and tissue remodeling with particular attention to vascularization. While we focus in this review on silkworm silk fibroin protein due to the large quantity of in vivo data thanks to its widespread use in medical materials and consumer products, spider silk information is also included if available. Silk proteins are degraded in the body on a time course that is dependent on the method of silk fabrication and can range from hours to years. Silk protein typically induces a mild inflammatory response that decreases within a few weeks of implantation. The response involves recruitment and activation of macrophages and may include activation of a mild foreign body response with the formation of multinuclear giant cells, depending on the material format and location of implantation. The no. of immune cells present decreases with time and granulation tissue, if formed, is replaced by endogenous, not fibrous, tissue. Importantly, silk materials have not been demonstrated to induce mineralization, except when used in calcified tissues. Due to its ability to be degraded, silk can be remodeled in the body allowing for vascularization and tissue ingrowth with eventual complete replacement by native tissue. The degree of remodeling, tissue ingrowth, or other specific cell behaviors can be modulated with addn. of growth or other signaling factors. Silk can also be combined with numerous other materials including proteins, synthetic polymers, and ceramics to enhance its characteristics for a particular function. Overall, the diverse array of silk materials shows excellent bioresponses in vivo with low immunogenicity and the ability to be remodeled and replaced by native tissue making it suitable for numerous clin. applications.
- 73Murphy, A. R.; Kaplan, D. L. Biomedical applications of chemically-modified silk fibroin. J. Mater. Chem. 2009, 19, 6443– 6450, DOI: 10.1039/b905802hGoogle Scholar73https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1MXhtVOnu7fN&md5=06ce00a9706a565f9f2f57675b45c542Biomedical applications of chemically-modified silk fibroinMurphy, Amanda R.; Kaplan, David L.Journal of Materials Chemistry (2009), 19 (36), 6443-6450CODEN: JMACEP; ISSN:0959-9428. (Royal Society of Chemistry)A review. Silk proteins belong to a class of unique, high mol. wt., block copolymer-like proteins that have found widespread use in biomaterials and regenerative medicine. The useful features of these proteins, including self-assembly, robust mech. properties, biocompatibility and biodegradability can be enhanced through a variety of chem. modifications. These modifications provide chem. handles for the attachment of growth factors, cell binding domains and other polymers to silk, expanding the range of cell and tissue engineering applications attainable. This review focuses on the chem. reactions that have been used to modify the amino acids in silk proteins, and describes their utility in biomedical applications.
- 74Liu, X. F.; Zhang, K. Q. Silk fiber - molecular formation mechanism, structure-property relationship and advanced applications. Oligomerization of Chemical and Biological Compounds 2014, 69– 102, DOI: 10.5772/57611Google Scholar74https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28XlvFGntrg%253D&md5=486e89539bdc76226f5b46e998b8c3a8Silk fiber - molecular formation mechanism, structure-property relationship and advanced applicationsLiu, Xinfang; Zhang, Ke-QinOligomerization of Chemical and Biological Compounds (2014), (), 69-102CODEN: 69UBNH ISSN:. (InTech)A review. This paper focuses on mol. formation mechanism, structure-property relationship and advanced applications of silk fibers. Silk protein assembly, silk fiber formation mechanism and structure and compn. of Bombyx mori and spider dragline silk fibers were also discussed.
- 75Nguyen, T. P.; Nguyen, Q. V.; Nguyen, V. H.; Le, T. H.; Huynh, V. Q. N.; Vo, D. V. N.; Trinh, Q. T.; Kim, S. Y.; Le, Q. V. Silk Fibroin-Based Biomaterials for Biomedical Applications: A Review. Polymers 2019, 11, 1933, DOI: 10.3390/polym11121933Google Scholar75https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1MXisVSiur7F&md5=3a30f84273eac5dfaf2599da4253eb15Silk fibroin-based biomaterials for biomedical applications: a reviewNguyen, Thang Phan; Nguyen, Quang Vinh; Nguyen, Van-Huy; Le, Thu-Ha; Huynh, Vu Quynh Nga; Vo, Dai-Viet N.; Trinh, Quang Thang; Kim, Soo Young; Van Le, QuyetPolymers (Basel, Switzerland) (2019), 11 (12), 1933CODEN: POLYCK; ISSN:2073-4360. (MDPI AG)A review. Since it was first discovered, thousands of years ago, silkworm silk has been known to be an abundant biopolymer with a vast range of attractive properties. The utilization of silk fibroin (SF), the main protein of silkworm silk, has not been limited to the textile industry but has been further extended to various high-tech application areas, including biomaterials for drug delivery systems and tissue engineering. The outstanding mech. properties of SF, including its facile processability, superior biocompatibility, controllable biodegrdn., and versatile functionalization have allowed its use for innovative applications. In this review, we describe the structure, compn., general properties, and structure-properties relationship of SF. In addn., the methods used for the fabrication and modification of various materials are briefly addressed. Lastly, recent applications of SF-based materials for small mol. drug delivery, biol. drug delivery, gene therapy, wound healing, and bone regeneration are reviewed and our perspectives on future development of these favorable materials are also shared.
- 76Jaramillo-Quiceno, N.; Restrepo-Osorio, A. Water-annealing treatment for edible silk fibroin coatings from fibrous waste. J. Appl. Polym. Sci. 2020, 137, 48505, DOI: 10.1002/app.48505Google Scholar76https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1MXhslOhurnP&md5=5cbf50df740941ac1399fdd4075301b5Water-annealing treatment for edible silk fibroin coatings from fibrous wasteJaramillo-Quiceno, N.; Restrepo-Osorio, A.Journal of Applied Polymer Science (2020), 137 (13), 48505CODEN: JAPNAB; ISSN:0021-8995. (John Wiley & Sons, Inc.)Silk fibroin (SF) is an engineered biopolymer with properties that are desirable for the development of food preservation materials, such as edible coatings or packaging. In this study, SF from fibrous waste was assessed for the first time as an edible coating for strawberries. Relationships were established between the structural properties of SF thin films obtained from silk waste, both untreated (SFW) and water annealed (WA-SFW) and their morphol. and performance as edible strawberry coatings. According to the results obtained, the water-annealing treatment led to a structural modification in SF films. The strawberries coated with WA-SFW exhibited better performance during storage by reducing wt. loss and preserving its visual appearance. The anal. of metal contaminants showed that SFs obtained from fibrous waste are relatively nontoxic. Therefore, using this raw material for the development of edible coatings in perishable fruits is considered promising. © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2019, 136, 48505.
- 77Sun, H.; Marelli, B. Growing silk fibroin in advanced materials for food security. MRS Commun. 2021, 11, 31– 45, DOI: 10.1557/s43579-020-00003-xGoogle Scholar77https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB38XjvFWrt78%253D&md5=76713e29d579ca656c7b0b6be8c5d01bGrowing silk fibroin in advanced materials for food securitySun, Hui; Marelli, BenedettoMRS Communications (2021), 11 (1), 31-45CODEN: MCROF8; ISSN:2159-6867. (Springer International Publishing AG)Abstr.: This perspective provides an overview of the micro-/nanofabrication methods developed for structural biopolymers, highlighting recent advances in the rapid and ease construction of complex and multifunctional silk fibroin-based devices by integrating top-down manufg. with bottom-up mol. self-assembly. Of particular interest is the development of a new nanofabrication strategy that employs templated crystn. to direct silk fibroin folding and assembly from a suspension of disordered, random coil mols. to ordered, hierarchical mesostructured materials. Such advancements in structural biopolymers fabrication provide the basis for engineering a new generation of tech. materials that can be interfaced with food and plants.
- 78Ruggeri, E.; Kim, D. Y.; Cao, Y. T.; Fare, S.; De Nardo, L.; Marelli, B. A multilayered edible coating to extend produce shelf life. ACS Sustain. Chem. Eng. 2020, 8, 14312– 14321, DOI: 10.1021/acssuschemeng.0c03365Google ScholarThere is no corresponding record for this reference.
- 79Tao, H.; Brenckle, M. A.; Yang, M. M.; Zhang, J. D.; Liu, M. K.; Siebert, S. M.; Averitt, R. D.; Mannoor, M. S.; McAlpine, M. C.; Rogers, J. A.; Kaplan, D. L.; Omenetto, F. G. Silk-based conformal, adhesive, edible food sensors. Adv. Mater. 2012, 24, 1067– 1072, DOI: 10.1002/adma.201103814Google Scholar79https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC38XhtFSnsLk%253D&md5=689c0895d06c048f2f6a798782897c93Silk-Based Conformal, Adhesive, Edible Food SensorsTao, Hu; Brenckle, Mark A.; Yang, Miaomiao; Zhang, Jingdi; Liu, Mengkun; Siebert, Sean M.; Averitt, Richard D.; Mannoor, Manu S.; McAlpine, Michael C.; Rogers, John A.; Kaplan, David L.; Omenetto, Fiorenzo G.Advanced Materials (Weinheim, Germany) (2012), 24 (8), 1067-1072CODEN: ADVMEW; ISSN:0935-9648. (Wiley-VCH Verlag GmbH & Co. KGaA)In this paper, the authors present a concept for making wireless passive antennas on silk substrates across multiple regions of the electromagnetic spectrum. These antennas can be easily applied to curved objects and adhere conformally. The devices were tested for function by monitoring their resonant responses continuously during spoilage process to assess the potential monitor changes in food quality. Proof-of-principle demonstrations for this type of approach are demonstrated by monitoring fruit ripening with a confromally attached RFID-like silk sensor transferred onto the fruit skin, and spoilage of dairy products through surface contact (in the solid fcase) or immersion (for liq. goods). These types of passive, chip-less sensor, consists of an antenna or an array of antennas/resonators made of only a sub-micron thickness of gold, a level equiv. to common edible gold leaf/flakes used on cakes and chocolates. The resonators are fabricated on pure-protein silk film substrates, and can be used as sensing platforms that safely interface with consumable goods or can be in direct contact with food (and can potentially be consumed) for different applications.
- 80Marelli, B.; Brenckle, M. A.; Kaplan, D. L.; Omenetto, F. G. Silk fibroin as edible coating for perishable food preservation. Sci. Rep. 2016, 6, 25263, DOI: 10.1038/srep25263Google Scholar80https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28XnsV2jtbg%253D&md5=dc0c0924e7ec68ec9f4e4adaf3c9114bSilk Fibroin as Edible Coating for Perishable Food PreservationMarelli, B.; Brenckle, M. A.; Kaplan, D. L.; Omenetto, F. G.Scientific Reports (2016), 6 (), 25263CODEN: SRCEC3; ISSN:2045-2322. (Nature Publishing Group)The regeneration of structural biopolymers into micelles or nanoparticles suspended in water has enabled the design of new materials with unique and compelling properties that can serve at the interface between the biotic and the abiotic worlds. In this study, we leveraged silk fibroin quintessential properties (i.e. polymorphism, conformability and hydrophobicity) to design a water-based protein suspension that self-assembles on the surface of food upon dip coating. The water-based post-processing control of the protein polymorphism enables the modulation of the diffusion of gases through the silk fibroin thin membranes (e.g. O2 and CO2 diffusion, water vapor permeability), which is a key parameter to manage food freshness. In particular, an increased beta-sheet content corresponds to a redn. in oxygen diffusion through silk fibroin thin films. By using the dip coating of strawberries and bananas as proof of principle, we have shown that the formation of micrometre-thin silk fibroin membranes around the fruits helps the management of postharvest physiol. of the fruits. Thus, silk fibroin coatings enhance fruits' shelf life at room conditions by reducing cell respiration rate and water evapn. The water-based processing and edible nature of silk fibroin makes this approach a promising alternative for food preservation with a naturally derived material.
- 81Leem, J. W.; Fraser, M. J.; Kim, Y. L. Transgenic and diet-enhanced silk production for reinforced biomaterials: A metamaterial perspective. Annu. Rev. Biomed. Eng. 2020, 22, 79– 102, DOI: 10.1146/annurev-bioeng-082719-032747Google Scholar81https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXks1Ojur0%253D&md5=a1d65d0f021ea0d24bd1e1952a19de42Transgenic and Diet-Enhanced Silk Production for Reinforced Biomaterials: A Metamaterial PerspectiveLeem, Jung Woo; Fraser, Malcolm J.; Kim, Young L.Annual Review of Biomedical Engineering (2020), 22 (), 79-102CODEN: ARBEF7; ISSN:1523-9829. (Annual Reviews)Silk fibers, which are protein-based biopolymers produced by spiders and silkworms, are fascinating biomaterials that have been extensively studied for numerous biomedical applications. Silk fibers often have remarkable phys. and biol. properties that typical synthetic materials do not exhibit. These attributes have prompted a wide variety of silk research, including genetic engineering, biotechnol. synthesis, and bioinspired fiber spinning, to produce silk proteins on a large scale and to further enhance their properties. In this review, we describe the basic properties of spider silk and silkworm silk and the important prodn. methods for silk proteins. We discuss recent advances in reinforced silk using silkworm transgenesis and functional additive diets with a focus on biomedical applications. We also explain that reinforced silk has an analogy with metamaterials such that user-designed atypical responses can be engineered beyond what naturally occurring materials offer. These insights into reinforced silk can guide better engineering of superior synthetic biomaterials and lead to discoveries of unexplored biol. and medical applications of silk.
- 82Elick, T. A.; Bauser, C. A.; Fraser, M. J. Excision of the piggyBac transposable element in vitro is a precise event that is enhanced by the expression of its encoded transposase. Genetica 1996, 98, 33– 41, DOI: 10.1007/BF00120216Google Scholar82https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaK28Xlslyntb8%253D&md5=023e75b34c00b99bbc55d7df713c76b0Excision of the piggyBac transposable element in vitro is a precise event that is enhanced by the expression of its encoded transposaseElick, Teresa A.; Bauser, Christopher A.; Fraser, M. J.Genetica (The Hague) (1996), 98 (1), 33-41CODEN: GENEA3; ISSN:0016-6707. (Kluwer)The piggyBac Lepidopteran transposable element moves from the cellular genome into infecting baculovirus genomes during passage of the virus in cultured TN-368 cells. We have constructed genetically tagged piggyBac elements that permit anal. of excision when transiently introduced on plasmids into the piggyBac-deficient Spodoptera frugiperda IPLB-SF21AE cell line. Precise excision of the element from these plasmids occurs at a higher frequency in the presence of a helper plasmid that presumably supplies the piggyBac transposase. The results suggest that the piggyBac transposon encodes a protein that functions to facilitate not only insertion, but precise excision as well. This is the first demonstration of piggyBac mobility from plasmid sources in uninfected Lepidopteran cells.
- 83Tamura, T.; Thibert, C.; Royer, C.; Kanda, T.; Eappen, A.; Kamba, M.; Komoto, N.; Thomas, J.-L.; Mauchamp, B.; Chavancy, G.; Shirk, P.; Fraser, M.; Prudhomme, J.-C.; Couble, P. Germline transformation of the silkworm Bombyx mori L. using a piggyBac transposon-derived vector. Nat. Biotechnol. 2000, 18, 81– 84, DOI: 10.1038/71978Google Scholar83https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BD3c%252FptFWnug%253D%253D&md5=9664d1a425972c400ba7f7a9e9b51fd0Germline transformation of the silkworm Bombyx mori L. using a piggyBac transposon-derived vectorTamura T; Thibert C; Royer C; Kanda T; Abraham E; Kamba M; Komoto N; Thomas J L; Mauchamp B; Chavancy G; Shirk P; Fraser M; Prudhomme J C; Couble P; Toshiki T; Chantal T; Corinne R; Toshio K; Eappen A; Mari K; Natuo K; Jean-Luc T; Bernard M; Gerard C; Paul S; Malcolm F; Jean-Claude P; Pierre CNature biotechnology (2000), 18 (1), 81-4 ISSN:1087-0156.We have developed a system for stable germline transformation in the silkworm Bombyx mori L. using piggyBac, a transposon discovered in the lepidopteran Trichoplusia ni. The transformation constructs consist of the piggyBac inverted terminal repeats flanking a fusion of the B. mori cytoplasmic actin gene BmA3 promoter and the green fluorescent protein (GFP). A nonautonomous helper plasmid encodes the piggyBac transposase. The reporter gene construct was coinjected into preblastoderm eggs of two strains of B. mori. Approximately 2% of the individuals in the G1 broods expressed GFP. DNA analyses of GFP-positive G1 silkworms revealed that multiple independent insertions occurred frequently. The transgene was stably transferred to the next generation through normal Mendelian inheritance. The presence of the inverted terminal repeats of piggyBac and the characteristic TTAA sequence at the borders of all the analyzed inserts confirmed that transformation resulted from precise transposition events. This efficient method of stable gene transfer in a lepidopteran insect opens the way for promising basic research and biotechnological applications.
- 84Li, X. H.; Burnight, E. R.; Cooney, A. L.; Malani, N.; Brady, T.; Sander, J. D.; Staber, J.; Wheelan, S. J.; Joung, J. K.; McCray, P. B.; Bushman, F. D.; Sinn, P. L.; Craig, N. L. piggyBac transposase tools for genome engineering. Proc. Natl. Acad. Sci. 2013, 110, E2279– E2287, DOI: 10.1073/pnas.1305987110Google Scholar84https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXhtFOmsLjK&md5=f337d469cb39a1bbb07a572d1d10ac62piggyBac transposase tools for genome engineeringLi, Xianghong; Burnight, Erin R.; Cooney, Ashley L.; Malani, Nirav; Brady, Troy; Sander, Jeffry D.; Staber, Janice; Wheelan, Sarah J.; Joung, J. Keith; McCray, Paul B., Jr.; Bushman, Frederic D.; Sinn, Patrick L.; Craig, Nancy L.Proceedings of the National Academy of Sciences of the United States of America (2013), 110 (25), E2279-E2287, SE2279/1-SE2279/8CODEN: PNASA6; ISSN:0027-8424. (National Academy of Sciences)The transposon piggyBac is being used increasingly for genetic studies. Here, the authors describe modified versions of piggyBac transposase that have potentially wide-ranging applications, such as reversible transgenesis and modified targeting of insertions. PiggyBac is distinguished by its ability to excise precisely, restoring the donor site to its pretransposon state. This characteristic makes piggyBac useful for reversible transgenesis, a potentially valuable feature when generating induced pluripotent stem cells without permanent alterations to genomic sequence. To avoid further genome modification following piggyBac excision by reintegration, the authors generated an excision competent/integration defective (Exc+Int-) transposase. Their findings also suggest the position of a target DNA-transposase interaction. Another goal of genome engineering is to develop reagents that can guide transgenes to preferred genomic regions. Others have shown that piggyBac transposase can be active when fused to a heterologous DNA-binding domain. An Exc+Int- transposase, the intrinsic targeting of which is defective, might also be a useful intermediate in generating a transposase whose integration activity could be rescued and redirected by fusion to a site-specific DNA-binding domain. Fusion to two designed zinc finger proteins rescued the Int- phenotype. Successful guided transgene integration into genomic DNA would have broad applications to gene therapy and mol. genetics. Thus, an Exc+Int- transposase is a potentially useful reagent for genome engineering and provides insight into the mechanism of transposase-target DNA interaction.
- 85Leem, J. W.; Allcca, A. E. L.; Kim, Y. J.; Park, J.; Kim, S. W.; Kim, S. R.; Ryu, W. H.; Chen, Y. P.; Kim, Y. L. Photoelectric silk via genetic encoding and bioassisted plasmonics. Adv. Biosyst. 2020, 4, 2000040, DOI: 10.1002/adbi.202000040Google Scholar85https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXhtl2gsrnN&md5=175389a77b1cd508998f69ac44e6c3cfPhotoelectric Silk via Genetic Encoding and Bioassisted PlasmonicsLeem, Jung Woo; Llacsahuanga Allcca, Andres E.; Kim, Yong Jae; Park, Jongwoo; Kim, Seong-Wan; Kim, Seong-Ryul; Ryu, WonHyoung; Chen, Yong P.; Kim, Young L.Advanced Biosystems (2020), 4 (7), 2000040CODEN: ABDIHL; ISSN:2366-7478. (Wiley-VCH Verlag GmbH & Co. KGaA)Genetically encoded photoelec. silk that can convert photons to electrons (light to electricity) over a wide visible range in a self-power mode is reported. As silk is a versatile host material with elec. cond., biocompatibility, and processability, a photoelec. protein is genetically fused with silk by silkworm transgenesis. Specifically, mKate2, which is conventionally known as a far-red fluorescent protein, is used as a photoelec. protein. Characterization of the electrochem. and optical properties of mKate2 silk allows designing a photoelec. measurement system. A series of in situ photocurrent expts. support the sensitive and stable performance of photoelec. conversion. In addn., as a plasmonic nanomaterial with a broad spectral resonance, titanium nitride (TiN) nanoparticles are biol. hybridized into the silk glands, taking full advantage of the silkworms' open circulatory system as well as the absorption band of mKate2 silk. This biol. hybridization via direct feeding of TiN nanoparticles further enhances the overall photoelec. conversion ability of mKate2 silk. It is envisioned that the biol. derived photoelec. protein, its ecofriendly scalable prodn. by transgenic silkworms, and the bioassisted plasmonic hybridization can potentially broaden the biomaterial choices for developing next-generation biosensing, retina prosthesis, and neurostimulation applications.
- 86Leem, J. W.; Choi, S. H.; Kim, S. R.; Kim, S. W.; Choi, K. H.; Kim, Y. L. Scalable and continuous nanomaterial integration with transgenic fibers for enhanced photoluminescence. Mater. Horiz. 2017, 4, 281– 289, DOI: 10.1039/C6MH00423GGoogle Scholar86https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXht1amtrg%253D&md5=957eb6d3f70529aabe9dca24b69141dfScalable and continuous nanomaterial integration with transgenic fibers for enhanced photoluminescenceLeem, Jung Woo; Choi, Seung Ho; Kim, Seong-Ryul; Kim, Seong-Wan; Choi, Kwang-Ho; Kim, Young L.Materials Horizons (2017), 4 (2), 281-289CODEN: MHAOBM; ISSN:2051-6355. (Royal Society of Chemistry)For widespread practical translation and utilization of plasmonics and nanophotonics, there is always a need for scalable, cost-effective, eco-friendly, and nontoxic prodn. of nanomaterials and nanostructures. As alternative fabrication and synthesis approaches, insects have received considerable attention as bioreactors and biosynthesis factories. However, scalable fabrication of plasmonic nanomaterials and their integration into flexible and wearable components are still limited. We show that a unique combination of a silkworm factory and green chem. appears to be an effective hybridizing platform for integrating natural biomaterials and metal nanoparticles. Our approach is inspired by a two-century-old method of increasing the wt. of silk fabrics for high price (also known as silk weighting). The reported plasmonics hybridization of silk results in the formation of silver nanoparticles in the interfibrillar space of silk fibers, which is manifested by the 'lustrous' or 'silvery' color of silk. We further demonstrate the plasmon-enhanced photoluminescence of far-red fluorescent protein in silk produced by genetically engineered silkworms (i.e., silkworm transgenesis). Our results provide the groundwork for exploiting native silk as a photonic hybridization platform to implement embedded functionalities in a fiber geometry, which could easily be woven or constructed into large-area and continuous fabrics using existing textile infrastructures in a sustainable manner.
- 87Tschorn, N.; Berg, K.; Stitz, J. Transposon vector-mediated stable gene transfer for the accelerated establishment of recombinant mammalian cell pools allowing for high-yield production of biologics. Biotechnol. Lett. 2020, 42, 1103– 1112, DOI: 10.1007/s10529-020-02889-yGoogle Scholar87https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXotVChsrs%253D&md5=afc64d72788bd460298d9820fe493633Transposon vector-mediated stable gene transfer for the accelerated establishment of recombinant mammalian cell pools allowing for high-yield production of biologicsTschorn, Natalie; Berg, Karen; Stitz, JoernBiotechnology Letters (2020), 42 (7), 1103-1112CODEN: BILED3; ISSN:0141-5492. (Springer)A review. Stable recombinant mammalian cells are of growing importance in pharmaceutical biotechnol. prodn. scenarios for biologics such as monoclonal antibodies, growth and blood factors, cytokines and subunit vaccines. However, the establishment of recombinant producer cells using classical stable transfection of plasmid DNA is hampered by low stable gene transfer efficiencies. Consequently, subsequent selection of transgenic cells and the screening of clonal cell populations are time- and thus cost-intensive. To overcome these limitations, expression cassettes were embedded into transposon-derived donor vectors. Upon the co-transfection with transposase-encoding constructs, elevated vector copy nos. stably integrated into the genomes of the host cells are readily achieved facilitating under stringent selection pressure the establishment of cell pools characterized by sustained and high-yield recombinant protein prodn. Here, we discuss some aspects of transposon vector technologies, which render these vectors promising candidates for their further utilization in the prodn. of biologics.
- 88Jang, K. M.; Kim, S. G.; Park, J. Y.; Choi, W. H.; Lee, J. W.; Jegal, H. Y.; Kweon, S. J.; Choi, K. H.; Park, J. H. Single-dose oral toxicity study of genetically modified silkworm expressing EGFP protein in icr mouse. Korean J. Agric. Sci. 2016, 43, 109– 115, DOI: 10.7744/kjoas.20160013Google Scholar88https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXhsVGgtb7K&md5=f6cf4b007b6e94f752067bf7d11d16e6Single-dose oral toxicity study of genetically modified silkworm expressing EGFP protein in ICR mouseJang, Kyung-min; Kim, Sung-Gun; Park, Ji-Young; Choi, Won-Ho; Lee, Jae-Woo; Jegal, Hyeon-Young; Kweon, Soon-jong; Choi, Kwang-ho; Park, Jung-hoKorean Journal of Agricultural Science (2016), 43 (1), 109-115CODEN: KJASAP; ISSN:2466-2410. (CNU Institute of Agricultural Science)Silk has had a reputation as a luxurious and sensuous fabric but it is not popular due to the expensive price and poor durability. To develop the silk materials that apply the various industries, the artificially synthesized gene can be introduced into the silkworm and expressed in the silk gland. Transgenic silkworms for the mass prodn. of green fluorescent silks are generated using a fibroin H-chain expression system. For com. use, safety assessment of the transgenic silkworms is essential. The purpose of this study was to examine the potential acute oral toxicity of EGFP protein expressed in genetically modified (GM) fluorescence silkworm and to obtain the approximative LD in the male and female at 6-wk ICR mice. EGFP protein was fed at a dose of 2,000 mg/kg body wt. in five male or five female mice. Mortalities, clin. findings and body wt. changes were monitored for 1, 3, 7, 14 days after dosing. At the end of 14 day observation period, all mice were sacrificed, and the postmortem necropsy were performed. The test group was not obsd. death case. Also the effect was not admitted by test substance administration in common symptoms, the body wt. and postmortem. The results of single-dose oral toxicity test showed that approximative LD of EGFP protein expressed in fluorescence silkworm was considered to exceed the 2,000 mg/kg body wt. in both sexes.
- 89Richards, H. A.; Han, C. T.; Hopkins, R. G.; Failla, M. L.; Ward, W. W.; Stewart, C. N. Safety assessment of recombinant green fluorescent protein orally administered to weaned rats. J. Nutr. 2003, 133, 1909– 1912, DOI: 10.1093/jn/133.6.1909Google Scholar89https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD3sXks1Grsr8%253D&md5=91977091dcc87c928350fa5a6ed3bbf7Safety assessment of recombinant green fluorescent protein orally administered to weaned ratsRichards, Harold A.; Han, Chung-Ting; Hopkins, Robin G.; Failla, Mark L.; Ward, William W.; Stewart, C. Neal, Jr.Journal of Nutrition (2003), 133 (6), 1909-1912CODEN: JONUAI; ISSN:0022-3166. (American Society for Nutritional Sciences)Several proposed biotechnol. applications of green fluorescent protein (GFP) are likely to result in its introduction into the food supply of domestic animals and man. We fed pure GFP and diets contg. transgenic canola expressing GFP to young 4-wk-old male Long-Evans Hooded rats for 26 days to evaluate the potential toxicity and allergenicity of GFP. Animals (n = 8/group) were fed AIN-93G diet (control), control diet plus 1.0 mg purified GFP daily, modified control diet with 200 g canola (Brassica rapa cultivar Westar)/kg feed, or control diet with 200 g transgenic canola with 2 levels of GFP/kg feed. Ingestion of GFP did not affect growth, food intake, relative wt. of intestine or other organs, or activities of hepatic enzymes in blood serum. Comparison of the amino acid sequence of GFP to known food allergens revealed that the greatest no. of consecutive amino acid matches between GFP and any food allergen was 4, suggesting the absence of common allergen epitopes. GFP was rapidly degraded during simulated gastric digestion. The data indicate that GFP is a low allergenicity risk and provide preliminary indications that GFP is not likely to pose a health risk.
- 90Kim, D. W.; Lee, O. J.; Kim, S. W.; Ki, C. S.; Chao, J. R.; Yoo, H.; Yoon, S. I.; Lee, J. E.; Park, Y. R.; Kweon, H.; Lee, K. G.; Kaplan, D. L.; Park, C. H. Novel fabrication of fluorescent silk utilized in biotechnological and medical applications. Biomaterials 2015, 70, 48– 56, DOI: 10.1016/j.biomaterials.2015.08.025Google Scholar90https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXhtlCksbfI&md5=49dbf2b254e576ae3db706cf9bc97f31Novel fabrication of fluorescent silk utilized in biotechnological and medical applicationsKim, Dong Wook; Lee, Ok Joo; Kim, Seong-Wan; Ki, Chang Seok; Chao, Janet Ren; Yoo, Hyojong; Yoon, Sung-il; Lee, Jeong Eun; Park, Ye Ri; Kweon, HaeYong; Lee, Kwang Gill; Kaplan, David L.; Park, Chan HumBiomaterials (2015), 70 (), 48-56CODEN: BIMADU; ISSN:0142-9612. (Elsevier Ltd.)Silk fibroin (SF) is a natural polymer widely used and studied for diverse applications in the biomedical field. Recently, genetically modified silks, particularly fluorescent SF fibers, were reported to have been produced from transgenic silkworms. However, they are currently limited to textile manufg. To expand the use of transgenic silkworms for biomedical applications, a soln. form of fluorescent SF needed to be developed. Here, we describe a novel method of prepg. a fluorescent SF soln. and demonstrate long-term fluorescent function up to one year after s.c. insertion. We also show that fluorescent SF labeled p53 antibodies clearly identify HeLa cells, indicating the applicability of fluorescent SF to cancer detection and bio-imaging. Furthermore, we demonstrate the intraoperative use of fluorescent SF in an animal model to detect a small esophageal perforation (0.5 mm). This study suggests how fluorescent SF biomaterials can be applied in biotechnol. and clin. medicine.
- 91Leem, J. W.; Park, J.; Kim, S. W.; Kim, S. R.; Choi, S. H.; Choi, K. H.; Kim, Y. L. Green light-activated photoreaction via genetic hybridization of far-red fluorescent protein and silk. Adv. Sci. 2018, 5, 1700863, DOI: 10.1002/advs.201700863Google Scholar91https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BB3c%252FhtlOhug%253D%253D&md5=fcb1607d1d6f6bcc00ff45eed9679c8eGreen-Light-Activated Photoreaction via Genetic Hybridization of Far-Red Fluorescent Protein and SilkLeem Jung Woo; Choi Seung Ho; Kim Young L; Park Jongwoo; Kim Seong-Wan; Kim Seong-Ryul; Choi Kwang-Ho; Kim Young L; Kim Young LAdvanced science (Weinheim, Baden-Wurttemberg, Germany) (2018), 5 (6), 1700863 ISSN:2198-3844.Fluorescent proteins often result in phototoxicity and cytotoxicity, in particular because some red fluorescent proteins produce and release reactive oxygen species (ROS). The photogeneration of ROS is considered as a detrimental side effect in cellular imaging or is proactively utilized for ablating cancerous tissue. As ancient textiles or biomaterials, silk produced by silkworms can directly be used as fabrics or be processed into materials and structures to host other functional nanomaterials. It is reported that transgenic fusion of far-red fluorescent protein (mKate2) with silk provides a photosensitizer hybridization platform for photoinducible control of ROS. Taking advantage of green (visible) light activation, native and regenerated mKate2 silk can produce and release superoxide and singlet oxygen, in a comparable manner of visible light-driven plasmonic photocatalysis. Thus, the genetic expression of mKate2 in silk offers immediately exploitable and scalable photocatalyst-like biomaterials. It is further envisioned that mKate2 silk can potentially rule out hazardous concerns associated with foreign semiconductor photocatalytic nanomaterials.
- 92Marcinkevicius, P.; Bagci, I. B.; Abdelazim, N. M.; Woodhead, C. S.; Young, R. J.; Roedig, U. Optically Interrogated Unique Object with Simulation Attack Prevention; Design, Automation & Test in Europe Conference & Exhibition (DATE), Florence, Italy, 2019.Google ScholarThere is no corresponding record for this reference.
- 93Park, J.; Leem, J. W.; Ku, Z. Y.; Kim, J. O.; Chegal, W. C.; Kang, S. W.; Kim, Y. L. Disordered heteronanostructures of MoS2 and TiO2 for unclonable cryptographic primitives. ACS Appl. Nano Mater. 2021, 4, 2076– 2085, DOI: 10.1021/acsanm.0c03367Google Scholar93https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3MXislGjsLc%253D&md5=6a1efeed69384de3db6862e715b7ccc0Disordered Heteronanostructures of MoS2 and TiO2 for Unclonable Cryptographic PrimitivesPark, Jaeseo; Leem, Jung Woo; Ku, Zahyun; Kim, Jun Oh; Chegal, Won C.; Kang, Sang-Woo; Kim, Young L.ACS Applied Nano Materials (2021), 4 (2), 2076-2085CODEN: AANMF6; ISSN:2574-0970. (American Chemical Society)In the era of hyperconnected contemporary society, hardware and information security become more dependent on advanced cryptog. primitives. A phys. unclonable function (PUF), originally implemented by an algorithmic means as software-based security, is considered as an immediate security soln. Nanomaterial-based PUFs have recently received considerable attention but have often limitations on unclonability and scalability for practical applications. Here, we report that heteronanostructures of vertically orientated molybdenum disulfide (MoS2) nanoflakes and titanium dioxide (TiO2) aggregates can be used for a versatile PUF. The band alignment of heteronanostructured MoS2/TiO2 results in photogenerated electron transfer and turns off the bright state of emitters, offering an entropy source. After von Neumann debiasing, extd. cryptog. keys show a large encoding capacity and reliable PUF performance, including randomness, uniqueness, reproducibility, low false rates, and long-term stability. The unique hybridization of the most common semiconductor nanomaterials could not only offer inherent asymmetry not to be cloned for a PUF but also guarantee scalable nanomanufg. strategies to augment cryptosystems.
- 94Leem, J. W.; Choi, M.; Yu, J. S. Multifunctional microstructured polymer films for boosting solar power generation of silicon-based photovoltaic modules. ACS Appl. Mater. Interfaces 2015, 7, 2349– 2358, DOI: 10.1021/am5068194Google Scholar94https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXhsF2jtLY%253D&md5=9fe9e7c90a7c8672673087f5b9542460Multifunctional Microstructured Polymer Films for Boosting Solar Power Generation of Silicon-Based Photovoltaic ModulesLeem, Jung Woo; Choi, Minkyu; Yu, Jae SuACS Applied Materials & Interfaces (2015), 7 (4), 2349-2358CODEN: AAMICK; ISSN:1944-8244. (American Chemical Society)The authors propose 2-dimensional periodic conical micrograting structured (MGS) polymer films as a multifunctional layer (i.e., light harvesting and self-cleaning) at the surface of outer polyethylene terephthalate (PET) cover-substrates for boosting the solar power generation in Si-based photovoltaic (PV) modules. The surface of UV-curable NOA63 MGS polymer films fabricated by the soft imprint lithog. exhibits a hydrophobic property with H2O contact angle of ∼121° at no inclination and dynamic advancing/receding H2O contact angles of ∼132°/111° at the inclination angle of 40°, resp., which can remove dust particles or contaminants on the surface of PV modules in real outdoor environments (i.e., self-cleaning). The NOA63 MGS film coated on the bare PET leads to the redn. of reflection as well as the enhancement of both the total and diffuse transmissions at wavelengths of 300-1100 nm, indicating lower solar weighted reflectance (RSW) of ∼8.2%, higher solar weighted transmittance (TSW) of ∼93.1%, and considerably improved av. haze ratio (HAvg) of ∼88.3% as compared to the bare PET (i.e., RSW ≈ 13.5%, TSW ≈ 86.9%, and HAvg ≈ 9.1%), resp. Addnl., it shows a relatively good durability at temps. of ≤160°. The resulting Si PV module with the NOA63 MGS/PET has an enhanced power conversion efficiency (PCE) of 13.26% (cf., PCE = 12.55% for the ref. PV module with the bare PET) due to the mainly improved short circuit current from 49.35 to 52.01 mA, exhibiting the PCE increment percentage of ∼5.7%. For light incident angle-dependent PV module current-voltage characteristics, superior solar energy conversion properties are also obtained in a broad angle range of 10-80°.
- 95Leem, J. W.; Lee, S. H.; Guan, X. Y.; Yu, J. S. Inverted tetrahedron-pyramidal micropatterned polymer films for boosting light output power in flip-chip light-emitting diodes. Opt. Express 2015, 23, 9612– 9617, DOI: 10.1364/OE.23.009612Google Scholar95https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXksFWhsrw%253D&md5=ab4628638e6ee8867eb6db25f6c0466eInverted tetrahedron-pyramidal micropatterned polymer films for boosting light output power in flip-chip light-emitting diodesLeem, Jung Woo; Lee, Soo Hyun; Guan, Xiang-Yu; Yu, Jae SuOptics Express (2015), 23 (8), 9612-9617CODEN: OPEXFF; ISSN:1094-4087. (Optical Society of America)We report the improved light output power in gallium nitridebased green flip-chip light-emitting diodes (FCLEDs) employed with inverted tetrahedron-pyramidal micropatterned polydimethylsiloxane (ITPM PDMS) films as an encapsulation and protection layer. The micropatterns are transferred into the surface of PDMS films from the sapphire substrate master molds with two-dimensional periodic hexagonal TPM arrays by a soft imprint lithog. method. The ITPM PDMS film laminated on the sapphire dramatically enhances the diffuse transmittance (TD) in a wavelength (λ) range of 400-650 nm, exhibiting the larger TD value of ∼53% at λ = 525 nm, (cf., TD ∼1% for planar sapphire). By introducing the ITPM PDMS film on the outer surface of sapphire in FCLEDs, the light output power is enhanced, indicating the increment percentage of ∼11.1% at 500 mA of injection current compared to the ref. FCLED without the ITPM PDMS film, together with better electroluminescence intensity and far-field radiation pattern.
- 96Nogueira, G. M.; Rodas, A. C. D.; Leite, C. A. P.; Giles, C.; Higa, O. Z.; Polakiewicz, B.; Beppu, M. M. Preparation and characterization of ethanol-treated silk fibroin dense membranes for biomaterials application using waste silk fibers as raw material. Bioresour. Technol. 2010, 101, 8446– 8451, DOI: 10.1016/j.biortech.2010.06.064Google Scholar96https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3cXoslyns70%253D&md5=b1f0e89090b5ee1730c46f7f2bd67989Preparation and characterization of ethanol-treated silk fibroin dense membranes for biomaterials application using waste silk fibers as raw materialNogueira, Grinia M.; Rodas, Andrea C. D.; Leite, Carlos A. P.; Giles, Carlos; Higa, Olga Z.; Polakiewicz, Bronislaw; Beppu, Marisa M.Bioresource Technology (2010), 101 (21), 8446-8451CODEN: BIRTEB; ISSN:0960-8524. (Elsevier Ltd.)The possibility of producing valued devices from low cost natural resources is a subject of broad interest. The present study explores the prepn. and characterization of silk fibroin dense membranes using waste silk fibers from textile processing. Morphol., crystallinity, thermal resistance and cytotoxicity of membranes as well as the changes on the secondary structure of silk fibroin were analyzed after undergoing treatment with ethanol. Membranes presented amorphous patterns as detd. via X-ray diffraction. The secondary structure of silk fibroin on dense membranes was either random coil (silk I) or β-sheet (silk II), before and after ethanol treatment, resp. The sterilized membranes presented no cytotoxicity to endothelial cells during in vitro assays. This fact stresses the material potential to be used in the fabrication of biomaterials, as coatings of cardiovascular devices and as membranes for wound dressing or drug delivery systems.
- 97Qi, Y.; Wang, H.; Wei, K.; Yang, Y.; Zheng, R. Y.; Kim, I. S.; Zhang, K. Q. A review of structure construction of silk fibroin biomaterials from single structures to multi-level structures. Int. J. Mol. Sci. 2017, 18, 237, DOI: 10.3390/ijms18030237Google Scholar97https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1cXkvVShsrg%253D&md5=9837f43dc3bd91ae5f81e72a30508acaA review of structure construction of silk fibroin biomaterials from single structures to multi-level structuresQi, Yu; Wang, Hui; Wei, Kai; Yang, Ya; Zheng, Ru-Yue; Kim, Ick Soo; Zhang, Ke-QinInternational Journal of Molecular Sciences (2017), 18 (3), 237/1-237/21CODEN: IJMCFK; ISSN:1422-0067. (MDPI AG)The biol. performance of artificial biomaterials is closely related to their structure characteristics. Cell adhesion, migration, proliferation, and differentiation are all strongly affected by the different scale structures of biomaterials. Silk fibroin (SF), extd. mainly from silkworms, has become a popular biomaterial due to its excellent biocompatibility, exceptional mech. properties, tunable degrdn., ease of processing, and sufficient supply. As a material with excellent processability, SF can be processed into various forms with different structures, including particulate, fiber, film, and three-dimensional (3D) porous scaffolds. This review discusses and summarizes the various constructions of SF-based materials, from single structures to multi-level structures, and their applications. In combination with single structures, new techniques for creating special multi-level structures of SF-based materials, such as micropatterning and 3D-printing, are also briefly addressed.
- 98Kaewpirom, S.; Boonsang, S. Influence of alcohol treatments on properties of silk-fibroin-based films for highly optically transparent coating applications. RSC Adv. 2020, 10, 15913– 15923, DOI: 10.1039/D0RA02634DGoogle Scholar98https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXnsFSruro%253D&md5=b9c932186edd61aea6af504fe343a036Influence of alcohol treatments on properties of silk-fibroin-based films for highly optically transparent coating applicationsKaewpirom, Supranee; Boonsang, SiridechRSC Advances (2020), 10 (27), 15913-15923CODEN: RSCACL; ISSN:2046-2069. (Royal Society of Chemistry)Thin films of silk fibroin were prepd. by solvent evapn. from calcium chloride/ethanol aq. soln. The influence of alc. treatments on thermal, mech. and optical properties of silk-fibroin-based film is presented. To understand the conformal structure of the alc.-treated silk fibroin film, the IR spectral decompn. method is employed. The optical properties esp. the optical transparency, haze and fluorescence emission of alc.-treated silk fibroin film is systematically investigated together with the conformal structure to understand the effect of the fibril such as the beta-sheet influencing the optical properties. Monohydric alc. treatment increased beta-turn content in the regenerated silk fibroin structure. The ethanol-treated silk-fibroin films displayed a distinct interference of oscillating crests and troughs in the UV-Vis transmittance spectra, thereby showing the lowest optical haze of 2.56%. In contrast, the silk-fibroin films treated with methanol and propanol exhibit the highest (14.17%) and second-highest (10.29%) optical transmittance haze, resp. These results show the relationship between the beta-turn content and optical haze properties. The results manifestly provide a method to manuf. exceptional optically transparent silk-fibroin films with adjustable light diffusion and scattering which can be designed to meet specific applications with the potential to provide UV-shielding protection via monohydric alc. treatment.
- 99Parker, W. A. Alcohol-containing pharmaceuticals. Am. J. Drug Alcohol. Ab. 1982, 9, 195– 209, DOI: 10.3109/00952998209002622Google ScholarThere is no corresponding record for this reference.
- 100Liquid Medicine May Contain a High Level of Alcohol. Use with Caution When Administering to a Child; ConsumerMedSafety (Accessed July 2021).Google ScholarThere is no corresponding record for this reference.
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- 102Marelli, B.; Patel, N.; Duggan, T.; Perotto, G.; Shirman, E.; Li, C. M.; Kaplan, D. L.; Omenetto, F. G. Programming function into mechanical forms by directed assembly of silk bulk materials. P. Natl. Acad. Sci. 2017, 114, 451– 456, DOI: 10.1073/pnas.1612063114Google ScholarThere is no corresponding record for this reference.
- 103Jeong, L.; Lee, K. Y.; Liu, J. W.; Park, W. H. Time-resolved structural investigation of regenerated silk fibroin nanofibers treated with solvent vapor. Int. J. Biol. Macromol. 2006, 38, 140– 144, DOI: 10.1016/j.ijbiomac.2006.02.009Google Scholar103https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD28Xjs1yntro%253D&md5=2cc5a3b49fb01ff794bad95df78a253bTime-resolved structural investigation of regenerated silk fibroin nanofibers treated with solvent vaporJeong, Lim; Lee, Kuen Yong; Liu, Ju Whan; Park, Won HoInternational Journal of Biological Macromolecules (2006), 38 (2), 140-144CODEN: IJBMDR; ISSN:0141-8130. (Elsevier B.V.)Nonwoven matrixes of silk fibroin (SF) nanofibers were prepd. by electrospinning a regenerated SF soln., followed by treatment with solvent vapor including water, methanol, ethanol, and propanol. Structural changes of solvent vapor-treated SF nanofibers were investigated in a time-resolved manner using IR spectroscopy. Conformational transitions of SF nanofibers from random coil to β-sheet forms were dependent on the type of solvent vapor used, and their transition rates were strongly influenced by treatment temps. Consistent with previous findings, methanol vapor treatment provided a fast and effective means by which to alter the secondary structure of SF nanofibers. However, treatment with water vapor, as compared to treatment with alc. vapor, was also useful for inducing structural changes in SF nanofibers. As demonstrated in the present study, our approach of controlling secondary structure formation of proteins by solvent vapor treatment and monitoring real-time conformational changes may be useful for the design and tailoring of materials for biomedical applications.
- 104Dubey, P.; Chowdhury, P. K.; Ghosh, S. Modulation of Aggregation of Silk Fibroin by Synergistic Effect of the Complex of Curcumin and Beta-Cyclodextrin. BBA-Proteins Proteom. 2019, 1867, 416– 425, DOI: 10.1016/j.bbapap.2019.01.009Google ScholarThere is no corresponding record for this reference.
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- 107Lachenmeier, D. W.; Neufeld, M.; Rehm, J. The impact of unrecorded alcohol use on health: What do we know in 2020?. J. Stud. Alcohol Drugs 2021, 82, 28– 41, DOI: 10.15288/jsad.2021.82.28Google Scholar107https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BB3snivFyqug%253D%253D&md5=6cee6417ce0c92a36a119052d4073486The Impact of Unrecorded Alcohol Use on Health: What Do We Know in 2020?Lachenmeier Dirk W; Neufeld Maria; Neufeld Maria; Rehm Jurgen; Neufeld Maria; Rehm Jurgen; Rehm Jurgen; Rehm Jurgen; Rehm Jurgen; Rehm Jurgen; Rehm Jurgen; Rehm JurgenJournal of studies on alcohol and drugs (2021), 82 (1), 28-41 ISSN:.OBJECTIVE: About 25% of global alcohol consumption is unrecorded, that is, concerns alcohol not registered in the country where it is consumed. Unrecorded alcohol includes homemade, illicit, or surrogate alcohols. The aim of this review is to update the evidence on unrecorded alcohol and its impact on health. METHOD: A narrative review and qualitative synthesis of scientific literature (English and Russian) for the period 2016-2020 was conducted. RESULTS: A total of 100 articles were included in the synthesis. The most harm because of unrecorded alcohol seems to be caused by ethanol, although single and mass methanol poisonings constitute exceptions. Nevertheless, unrecorded consumption is associated with disproportionate harm that goes beyond toxicity, which is linked to hazardous drinking patterns of unrecorded alcohol, and its association with alcohol use disorders and social marginalization. The online sale of unrecorded alcohol, which circumvents alcohol availability regulations, is an emerging and not yet well-explored issue. CONCLUSIONS: Policy options include restricting access to methanol, increasing taxation, denaturing ethanol-containing liquids that could be used as surrogates, introducing more effective and less toxic denaturizing additives, and improving monitoring systems for fraud, tax evasion, and local sales restrictions, including raising the minimum legal drinking age. These measures should be implemented within a holistic policy framework to avoid unintended effects, such as an increase in total alcohol consumption, shifts from certain types of unrecorded products to potentially toxic alternatives, or limiting economic activity and jeopardizing the livelihoods of vulnerable populations (e.g., women comprise the majority of those making homebrew in some countries).
- 108McKee, M.; Adany, R.; Leon, D. A. Illegally produced alcohol. Br. Med. J. 2012, 344, e1146 DOI: 10.1136/bmj.e1146Google ScholarThere is no corresponding record for this reference.
- 109Spencer, J.; Lord, N.; Benson, K.; Bellotti, E. ‘C’ is for commercial collaboration: Enterprise and structure in the ‘middle market’ of counterfeit alcohol distribution. Crime Law Soc. Change 2018, 70, 543– 560, DOI: 10.1007/s10611-018-9781-zGoogle ScholarThere is no corresponding record for this reference.
- 110Counterfeit Goods in the Uk, Who Is Buying What, and Why; pwc.co.uk, October, 2013; p 2.Google ScholarThere is no corresponding record for this reference.
- 111Scotch Whisky Economic Impact Report 2018; Scotch Whisky Association, scotch-whisky.org.uk/newsroom/scotch-whisky-economic-impact-report-2018 (Accessed July 20210.Google ScholarThere is no corresponding record for this reference.
- 112Breg, J. M.; Tymoczko, J. L.; Stryer, L. Section 23.1 Proteins Are Degraded to Amino Acids; Biochemistry, W. H. Freeman: New York, USA, 2002.Google ScholarThere is no corresponding record for this reference.
- 113Hamuro, Y.; Coales, S. J.; Molnar, K. S.; Tuske, S. J.; Morrow, J. A. Specificity of Immobilized Porcine Pepsin in H/D Exchange Compatible Conditions. Rapid Commun. Mass Spectrom. 2008, 22, 1041– 1046, DOI: 10.1002/rcm.3467Google Scholar113https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1cXksFWku7Y%253D&md5=8a3b158c0922c0a28ac01201a76f1ba8Specificity of immobilized porcine pepsin in H/D exchange compatible conditionsHamuro, Yoshitomo; Coales, Stephen J.; Molnar, Kathleen S.; Tuske, Steven J.; Morrow, Jeffrey A.Rapid Communications in Mass Spectrometry (2008), 22 (7), 1041-1046CODEN: RCMSEF; ISSN:0951-4198. (John Wiley & Sons Ltd.)Statistical anal. of data from 39 proteins (13,766 amino acid residues) digested with immobilized porcine pepsin under conditions compatible with hydrogen/deuterium (H/D) exchange (<1°, <30 s) was performed to examine pepsin cleavage specificity. The cleavage of pepsin was most influenced by the amino acid residue at position P1. Phe and Leu are favored residues each with a cleavage probability greater than 40%. His, Lys, Arg, or Pro residues prohibit cleavage when found at the P1 position. Pro also cannot be at position P2 (cleavage probability <0.3%). Occupation of the P3 position by His, Lys, or Arg, or occupation of the P2' position by Pro, also leads to very little cleavage (cleavage probability <1.7%). The av. cleavage probability over the entire data set was 13.6%, which is slightly lower than the value previously obtained by J. C. Powers et al. (14.8%). This is due, in part, to the larger protein sizes used in the current study. While the specificity of pepsin was similar to that previously obsd., higher selectivity was obsd. in the present study due to less exptl. variation in the conditions used to generate the authors' database.
- 114Rick, W. Trypsin. In Methods of Enzymatic Analysis; Bergmeyer, J. B. H. U., Grabl, M., Eds.; Verlag Chemie GmbH: Weinheim, Germany, 1974, Vol. 2.Google ScholarThere is no corresponding record for this reference.
- 115Li, X. Q.; Zhang, G. H.; Ngo, N.; Zhao, X. N.; Kain, S. R.; Huang, C. C. Deletions of the aequorea victoria green fluorescent protein define the minimal domain required for fluorescence. J. Biol. Chem. 1997, 272, 28545– 28549, DOI: 10.1074/jbc.272.45.28545Google Scholar115https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaK2sXntlCku7s%253D&md5=6efdfdd0b9f5406b04f66d9cd1e42638Deletions of the Aequorea victoria green fluorescent protein define the minimal domain required for fluorescenceLi, Xianqiang; Zhang, Guohong; Ngo, Nhatanh; Zhao, Xiaoning; Kain, Steven R.; Huang, Chiao-ChainJournal of Biological Chemistry (1997), 272 (45), 28545-28549CODEN: JBCHA3; ISSN:0021-9258. (American Society for Biochemistry and Molecular Biology)The Green Fluorescent Protein (GFP) from the jellyfish, A. victoria, is a widely used marker for gene expression and protein localization studies. Dissection of the structure of the protein would be expected to shed light on its potential applications to other fields such as the detection of protease activity. Using deletion anal., the authors defined the minimal domain in GFP required for fluorescence to amino acids 7-229. This domain starts at the middle of the 1st small α-helix at the N-terminus of GFP and ends immediately following the last β-sheet. Studies of the amino acids at both termini of the minimal domain revealed that positions 6 and 7 at the N-terminus were Glu-specific. Change of the Glu residues to other amino acids resulted in redn. of GFP fluorescence. Position 229 at the C-terminus of GFP, however, was nonspecific; the Ile could be replaced with other amino acids with no measurable loss of fluorescence. A total of only 15 terminal amino acids could be deleted from GFP without disrupting fluorescence, consistent with findings of a previous study of GFP crystal structure that a tightly packed structure exists in the protein. The authors also generated internal deletions within the loop regions of GFP according to its crystal structure and found that all such deletions eliminated GFP fluorescence.
- 116Patterson, G. H.; Knobel, S. M.; Sharif, W. D.; Kain, S. R.; Piston, D. W. Use of the green fluorescent protein and its mutants in quantitative fluorescence microscopy. Biophys. J. 1997, 73, 2782– 2790, DOI: 10.1016/S0006-3495(97)78307-3Google Scholar116https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaK2sXntF2hsLo%253D&md5=166ab34b861ba1fe81bc8549f3002727Use of the green fluorescent protein and its mutants in quantitative fluorescence microscopyPatterson, George H.; Knobel, Susan M.; Sharif, Wallace D.; Kain, Steven R.; Piston, David W.Biophysical Journal (1997), 73 (5), 2782-2790CODEN: BIOJAU; ISSN:0006-3495. (Biophysical Society)We have investigated properties relevant to quant. imaging in living cells of five green fluorescent protein (GFP) variants that have been used extensively or are potentially useful. We measured the extinction coeffs., quantum yields, pH effects, photobleaching effects, and temp.-dependent chromophore formation of wtGFP, αGFP (F99S/M153T/V163A), S65T, EGFP (S64L/S65T), and a blue-shifted variant, EBFP (F64L/S65T/Y66H/Y145F). Absorbance and fluorescence spectroscopy showed little difference between the extinction coeffs. and quantum yields of wtGFP and αGFP. In contrast, S65T and EGFP extinction coeffs. made them both ∼6-fold brighter than wtGFP when excited at 488 nm, and EBFP absorbed more strongly than the wtGFP when excited in the near-UV wavelength region, although it had a much lower quantum efficiency. When excited at 488 nm, the GFPs were all more resistant to photobleaching than fluorescein. However, the wtGFP and αGFP photobleaching patterns showed initial increases in fluorescence emission caused by photoconversion of the protein chromophore. The wtGFP fluorescence decreased more quickly when excited at 395 nm than 488 nm, but it was still more photostable than the EBFP when excited at this wavelength. The wtGFP and αGFP were quite stable over a broad pH range, but fluorescence of the other variants decreased rapidly below pH 7. When expressed in bacteria, chromophore formation in wtGFP and S65T was found to be less efficient at 37° than at 28°, but the other three variants showed little differences between 37° and 28°. In conclusion, no single GFP variant is ideal for every application, but each one offers advantages and disadvantages for quant. imaging in living cells.
- 117Malik, A.; Rudolph, R.; Sohling, B. Use of enhanced green fluorescent protein to determine pepsin at high sensitivity. Analyt. Biochem. 2005, 340, 252– 258, DOI: 10.1016/j.ab.2005.02.022Google Scholar117https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD2MXjtlWqtLs%253D&md5=c7439731cd231c8375ddc5a9da262886Use of enhanced green fluorescent protein to determine pepsin at high sensitivityMalik, Ajamaluddin; Rudolph, Rainer; Soehling, BrigitteAnalytical Biochemistry (2005), 340 (2), 252-258CODEN: ANBCA2; ISSN:0003-2697. (Elsevier)A fluorometric assay for pepsin and pepsinogen was developed using enhanced green fluorescent protein (EGFP) as a substrate. Acid denaturation of EGFP resulted in a complete loss of fluorescence that was completely reversible on neutralization. In the proteolytic assay procedure, acid-denatured EGFP was digested by pepsin or activated pepsinogen. After neutralization, the remaining amt. of undigested EGFP refolded and was detd. by fluorescence. Under std. digestion conditions, 4.8-24.0 ng pepsin or pepsinogen was used. Using porcine pepsin as a std., 38 ± 6.7 ng EGFP was digested per min/ng pepsin. Activated porcine pepsinogen revealed a similar digestion rate (37.2 ± 5.2 ng EGFP/min/ng activated pepsinogen). The sensitivity of the proteolysis assay depended on the time of digestion and the temp. Increasing the temp. and incubation time allowed quantification of pepsin or pepsinogen in a sample even in the picogram range. The pepsin-catalyzed EGFP digestion showed typical Michaelis-Menten kinetics. The Km and Vmax values were detd. for pepsin and activated pepsinogen. Digestion of EGFP by pepsin revealed distinct cleavage sites, as analyzed by SDS-PAGE.
- 118Mares, R. E.; Melendez-Lopez, S. G.; Ramos, M. A. Acid-denatured green fluorescent protein (GFP) as model substrate to study the chaperone activity of protein disulfide isomerase. Int. J. Mol. Sci. 2011, 12, 4625– 4636, DOI: 10.3390/ijms12074625Google Scholar118https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXhtVWqs73O&md5=08cf9db37efb6adc1cc6ee949ebb84dbAcid-denatured green fluorescent protein (GFP) as model substrate to study the chaperone activity of protein disulfide isomeraseMares, Rosa E.; Melendez-Lopez, Samuel G.; Ramos, Marco A.International Journal of Molecular Sciences (2011), 12 (), 4625-4636CODEN: IJMCFK; ISSN:1422-0067. (MDPI AG)Green fluorescent protein (GFP) has been widely used in several mol. and cellular biol. applications, since it is remarkably stable in vitro and in vivo. Interestingly, native GFP is resistant to the most common chem. denaturants; however, a low fluorescence signal has been obsd. after acid-induced denaturation. Furthermore, this acid-denatured GFP has been used as substrate in studies of the folding activity of some bacterial chaperones and other chaperone-like mols. Protein disulfide isomerase enzymes, a family of eukaryotic oxidoreductases that catalyze the oxidn. and isomerization of disulfide bonds in nascent polypeptides, play a key role in protein folding and it could display chaperone activity. However, contrasting results have been reported using different proteins as model substrates. Here, we report the further application of GFP as a model substrate to study the chaperone activity of protein disulfide isomerase (PDI) enzymes. Since refolding of acid-denatured GFP can be easily and directly monitored, a simple micro-assay was used to study the effect of the mol. participants in protein refolding assisted by PDI. Addnl., the effect of a well-known inhibitor of PDI chaperone activity was also analyzed. Because of the diversity their functional activities, PDI enzymes are potentially interesting drug targets. Since PDI may be implicated in the protection of cells against ER stress, including cancer cells, inhibitors of PDI might be able to enhance the efficacy of cancer chemotherapy; furthermore, it has been demonstrated that blocking the reductive cleavage of disulfide bonds of proteins assocd. with the cell surface markedly reduces the infectivity of the human immunodeficiency virus. Although several high-throughput screening (HTS) assays to test PDI reductase activity have been described, we report here a novel and simple micro-assay to test the chaperone activity of PDI enzymes, which is amenable for HTS of PDI inhibitors.
- 119Zhang, Y. Y.; Zhao, Y. L.; Song, B.; Liu, K. M.; Gu, J. M.; Yue, Y. Y.; Xiong, R. H.; Huang, C. B. UV-fluorescence probe for detection Ni2+ with colorimetric/spectral dual-mode analysis method and its practical application. Bioorg. Chem. 2021, 114, 105103, DOI: 10.1016/j.bioorg.2021.105103Google Scholar119https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3MXhsVWhsbzI&md5=a882f5aa879ed9e8858d2d724f312665UV-fluorescence probe for detection Ni2+ with colorimetric/spectral dual-mode analysis method and its practical applicationZhang, Yingying; Zhao, Yanliang; Song, Bo; Liu, Kunming; Gu, Jiamin; Yue, Yiying; Xiong, Ranhua; Huang, ChaoboBioorganic Chemistry (2021), 114 (), 105103CODEN: BOCMBM; ISSN:0045-2068. (Elsevier B.V.)Fluorescence probe combines with fluorescence imaging technol. has become the most powerful anal. method with their great advantages of high sensitivity and selectivity and real-time monitoring. Ni2+ is widely distributed in food, environment and living animals, thereof, it is of great significance for detection Ni2+ with high selectivity. Herein, a simple strategy is proposed to design and synthesiz a small mol. fluorescent probe Y1 by using "one-pot" method. The spectroscopic behaviors including UV-Vis absorption and fluorescence emission spectrum have been used to verify the feasibility of probe towards Ni2+ in water/EtOH (vol./vol. = 2:8) mixts. under neutral condition. As expected, Y1 offers high selectivity and sensitivity for detection Ni2+ in aq. soln. with a good linear relationship and low detection limit within Ni2+ concn. variation from 0 to 13 μM (DOL = 0.0038 μM, R2 = 0.9983). It is remarkable that Y1 can be applied for real-time visualization Ni2+ change in sprouted potato and zebrafish with great photo-stability, highlighting that the practicability and feasibility of Y1 to detect and monitor Ni2+ in the field of food industry and biomedical field.
- 1206.15 lighting. U.S. General Services Administration, gsa.gov/node/82715 (Accessed January 2022).Google ScholarThere is no corresponding record for this reference.
- 121Kim, S. W.; Yun, E. Y.; Choi, K. H.; Kim, S. R.; Kang, S. W.; Park, S. W.; Goo, T. W. Utilization of the Bombyx mori heat shock protein 70 promoter for screening transgenic silkworms. Entomolog.l Res. 2013, 43, 282– 287, DOI: 10.1111/1748-5967.12031Google ScholarThere is no corresponding record for this reference.
- 122Nagy, A.; Malnasi-Csizmadia, A.; Somogyi, B.; Lorinczy, D. Thermal stability of chemically denatured green fluorescent protein (GFP) - A preliminary study. Thermochim. Acta 2004, 410, 161– 163, DOI: 10.1016/S0040-6031(03)00397-6Google Scholar122https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD3sXpvFGhtLo%253D&md5=8a1a3cb6caa84f1db2f0b9e750662e1aThermal stability of chemically denatured green fluorescent protein (GFP). A preliminary studyNagy, Attila; Malnasi-Csizmadia, Andras; Somogyi, Bela; Lorinczy, DenesThermochimica Acta (2004), 410 (1-2), 161-163CODEN: THACAS; ISSN:0040-6031. (Elsevier Science B.V.)Green fluorescent protein (GFP) is a light emitter in the bioluminescence reaction of the jellyfish, Aequorea victoria. GFP consists of 238 amino acids and produces green fluorescent light (λmax = 508 nm), when irradiated with near-UV light. The fluorescence is due to the presence of a chromophore consisting of an imidazolone ring, formed by a post-translational modification of the tripeptide, -Ser65-Tyr66-Gly67-, which is buried in the β-barrel. GFP is an extremely compact and thermostable mol. Here, the authors present data for the effect of the chem. denaturing agent, guanidine-HCl (GuHCl), on the thermostability of GFP. When GuHCl was applied, the global thermostability and the melting temp. (Tm) of GFP decreased, and was monitored by DSC. The results indicated that in 1-6M concn. range of GuHCl, the Tm decreased continuously from 83 to 38°. An interesting finding was that the calcd. enthalpy (ΔH) decreased with GuHCl concn. up to 3M (5.6-0.2 kJ/mol), but at 4M GuHCl it jumped to 8.4, and at higher GuHCl concns. it fell to 1.1 kJ/mol. The 1st phenomenon, i.e., the decrease of the Tm with increasing GuHCl concn., could be easily explained by the effect of the extended chem. denaturation when lesser amts. of heat were required to diminish the remaining H-bonds in the β-barrel. The surprising increase in ΔH at 4M GuHCl could be the consequence of dimerization or formation of a stable complex between GFP and the denaturing agent as well as pptn. at an extreme GuHCl concn. The authors plan further expts. to elucidate the fluorescent consequence of these processes.
- 123Alkaabi, K. M.; Yafea, A.; Ashraf, S. S. Effect of pH on thermal- and chemical-induced denaturation of gfp. Appl. Biochem. Biotechnol. 2005, 126, 149– 156, DOI: 10.1385/ABAB:126:2:149Google Scholar123https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD2MXhtVWksr3F&md5=c1441d308b9f978d7836b75f75688efdEffect of pH on thermal- and chemical-induced denaturation of GFPAlkaabi, Klaithem M.; Yafea, Abeer; Ashraf, S. SalmanApplied Biochemistry and Biotechnology (2005), 126 (2), 149-156CODEN: ABIBDL; ISSN:0273-2289. (Humana Press Inc.)Green fluorescent protein (GFP) is an unusually stable autofluorescent protein that is increasingly being exploited for many applications. In this report, we have used fluorescence spectroscopy to study the effect of pH on the denaturation of GFP with sodium dodecyl sulfate (SDS), urea, and heat. Surprisingly, SDS (up to 0.5%) did not have any significant effect on the fluorescence of GFP in pH 7.5 or 8.5 buffers; however, at pH 6.5, the protein lost all fluorescence within 1 min of incubation. Similarly, incubation of GFP with 8 M urea at 50°C resulted in time-dependent denaturation of GFP, but only in pH 6.5 buffer. At higher pH values (pH 7.5 and pH 8.5), GFP was quite stable in 8 M urea at 50°C, showing only a slight decrease in fluorescence. Heat denaturation of GFP was found to be pH-dependent as well, with the denaturation being fastest at pH 6.5 as compared to pH 7.5 or pH 8.5. Like the denaturation studies, renaturation of heat-denatured GFP was most efficient at pH 8.5, followed by pH 7.5, and then pH 6.5. These results suggests that GFP undergoes a structural/stability shift between pH 6.5 and pH 7.5, with the GFP structure at pH 6.5 being very sensitive to denaturation by SDS, urea, and heat.
- 124Rockwood, D. N.; Preda, R. C.; Yucel, T.; Wang, X. Q.; Lovett, M. L.; Kaplan, D. L. Materials fabrication from Bombyx mori silk fibroin. Nat. Protoc. 2011, 6, 1612– 1631, DOI: 10.1038/nprot.2011.379Google Scholar124https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXht1CrsbzN&md5=f073189b8c31ae54201228efb0d66eaeMaterials fabrication from Bombyx mori silk fibroinRockwood, Danielle N.; Preda, Rucsanda C.; Yucel, Tuna; Wang, Xiao-Qin; Lovett, Michael L.; Kaplan, David L.Nature Protocols (2011), 6 (10), 1612-1631CODEN: NPARDW; ISSN:1750-2799. (Nature Publishing Group)Silk fibroin, derived from Bombyx mori cocoons, is a widely used and studied protein polymer for biomaterial applications. Silk fibroin has remarkable mech. properties when formed into different materials, demonstrates biocompatibility, has controllable degrdn. rates from hours to years and can be chem. modified to alter surface properties or to immobilize growth factors. A variety of aq. or org. solvent-processing methods can be used to generate silk biomaterials for a range of applications. In this protocol, the authors include methods to ext. silk from B. mori cocoons to fabricate hydrogels, tubes, sponges, composites, fibers, microspheres and thin films. These materials can be used directly as biomaterials for implants, as scaffolding in tissue engineering and in vitro disease models, as well as for drug delivery.
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Abstract
Figure 1
Figure 1. Schematic illustration of an edible matrix code for anticounterfeiting pharmaceutical products and on-dose (or in-dose) authentication. Like other machine-readable barcodes or 2D matrix codes (e.g., QR code), the proposed code is a method of digital information representation and data storage but has unique features to be edible, imperceptible, and multidimensional, using three different fluorescent natural biopolymers (i.e., silk fibroin and fluorescent protein). After being affixed to an individual medicine by the pharmaceutical manufacturer or the hospital pharmacy, this code becomes an integrated part of the medicine. The end user or consumer (e.g., patient) can use a smartphone camera to read the code (i.e., fluorescence images). A digitized key is generated from the code by a deep neural network for quick and accurate key extraction. The extracted digital key is converted to a cryptographic hashed key through a hash function. As a result, the patient can be empowered to authenticate the medicine with the necessary dose information immediately before oral intake.
Figure 2
Figure 2. Fabrication of edible matrix codes using silk fibroin genetically hybridized with fluorescent proteins. (a) Schematic representation of transformation vector structures for silkworm transgenesis, p3×P3-DsRed2-pFibH-eCFP for eCFP silk, p3×P3-DsRed2-pFibH-eGFP for eGFP silk, and p3×P3-eGFP-pFibH-mKate2 for mKate2 silk. Fibroin heavy chain promoter domain (pFibH, 1124 base pairs (bp)), N-terminal region 1 (NTR1, 142 bp), Intron (871 bp), N-terminal region 2 (NTR2, 417 bp), C-terminal region (CTR, 179 bp), poly(A) signal region (PolyA, 301 bp), enhanced cyan fluorescent protein (eCFP, 720 bp), enhanced green fluorescent protein (eGFP, 720 bp), monomeric far-red fluorescent protein (mKate2, 699 bp), inverted repeat sequences of piggyBac arms (ITR), 3×P3 promoter (273 bp), and Sv40 polyadenylation signal sequence (Sv40pA, 268 bp). Red fluorescent protein (DsRed2) is used only for a marker gene of eCFP and eGFP, while eGFP is utilized for a marker gene of mKate2. (b) Photographs and fluorescence images of eCFP silk, eGFP silk, and mKate2 silk cocoons, compared with a nontransgenic (wild-type) white silk cocoon. Each silk fibroin solution is regenerated from the corresponding silk cocoons. (c, d) Optical absorption (c) and fluorescence emission (d) spectra of fluorescent silk fibroin films fabricated using the regenerated eCFP silk (cyan), eGFP silk (green), and mKate2 silk (red) fibroin solutions. (e) Photographs and fluorescence images of three different fluorescent silk fibroin films and a white silk fibroin film using an appropriate set of optical excitation and emission. A set of an excitation source (λex) and an emission filter (λem) is used as follows: λex = 415 nm and λem = 460 nm, λex = 470 nm and λem = 525 nm, and λex = 530 nm and λem = 630 nm for eCFP silk, eGFP silk, and mKate2 silk, respectively. The thickness of the fluorescent silk fibroin films is 70 μm on average. (f) Scanning electron microscopy images of conical micrograting arrays with 2D periodic hexagonal patterns. The height and bottom diameter of each grating are 1.4 and 2.7 μm with a distance (i.e., period) between adjacent gratings of 2.9 μm. (g) Photographs of light propagation (green laser at λ = 532 nm) through bare (top) and micrograting patterned (bottom) silk fibroin films. (h) Photograph of 7 × 7 matrix codes fabricated using bare (left) and micrograting patterned (right) silk fibroin films, affixed onto the tablet-type medicine (oral solid dosage). The code pattern on the micrograting patterned silk fibroin film is covert and imperceptible due to the strong diffraction of light caused by the micrograting arrays.
Figure 3
Figure 3. Cryptographic key generation of an edible code with three distinct fluorescence colors and digital signature generation with a hash algorithm. (a) Extraction process of digitized output keys from raw fluorescence input images of a representative edible code (7 × 7 matrix). Three different fluorescence images are acquired with an optical set of excitation and emission: eCFP silk code pattern (cyan); λex = 415 nm and λem = 460 nm, eGFP silk code pattern (green); 470 and 525 nm, and mKate2 silk code pattern (red); 530 and 630 nm. Each code pattern generates a 49-bit long binary key Kb. The binary keys of three different codes are combined to a digitized key of 147 bits (Kb1 + Kb2 + Kb3). In the case of a 7 × 7 matrix code, the nominal encoding capacity is calculated to be 2147 (≈ 1.78 × 1044). (b) Convolutional neural network (CNN) architecture for output key extraction of an edible matrix code. A 2D CNN model consists of three convolutional layers and two fully connected layers (Table S1). Batch normalization is applied to each convolutional layer for faster and more stable training. After each batch normalization, the rectified linear unit (ReLU) activation function is applied, and max-pooling is performed. (c) Hashed key generation from the extracted digitized key via a cryptographic hash algorithm (e.g., MD5). Other strong hash functions can be used including SHA-256 and SHA-512. A hashed key can be used for authentication, ensuring key integrity and securing against unauthorized modifications.
Figure 4
Figure 4. Edible code applications for authentication using a smartphone. (a, b) Simulated on-dose authentication of medicines. (a) Photograph of on-dose authentication of medicines integrated with an edible code. (b) Simulated authentication process for an oral-dosage tablet-type medicine. A custom-built mobile application (app) consists of the following steps for an end user or consumer (Movie S1): launch the customized app, scan an edible code using a set of excitation (470 nm) and emission (525 nm) optical filters (Figure S11). Then, this mobile app authenticates the scanned code and further opens the embedded hyperlink to a webpage to confirm the genuine medicine information, such as product data (e.g., dosage strength, dose frequency, cautions, and expiration date), manufacturing details (e.g., location, date, batch, and lot number), and distribution path (e.g., country, distributor, and wholesaler). (c, d) Bottle-through edible code application for in-dose authentication of high-value alcoholic spirits. (c) Photograph of simulated in-dose authentication of a Scotch whisky bottle (e.g., 80 proof whisky, 40% alcohol per volume) that contains an edible code inside. To image the edible code through the bottle, the bottle is titled facing down. (d) Simulated authentication process for an alcoholic spirit containing an edible code inside. The customized mobile app can authenticate the scanned code and further inform the genuine product information (Movie S2), such as product data (e.g., type, ingredients, alcohol concentration, and cautions), manufacturing details (e.g., location, date, and serial number), and distribution path (e.g., country, distributor, and wholesaler).
Figure 5
Figure 5. Enzymatic digestibility and biocompatibility of all protein-based matrix codes. (a) Schematic illustration of the gastrointestinal tract (the stomach and the small intestine) where pepsin and trypsin are the major proteolytic enzymes produced for denaturation and degradation of dietary proteins. (b) Photographs and fluorescence images of eGFP silk fibroin films immersed in pepsin (pH 2.2) enzyme or trypsin (pH 7.2) enzyme solutions as a function of elapsed time. For comparison, buffer solutions with the same pH values without enzymes are tested. (c) Fluorescence emission intensity of eGFP silk fibroin films immersed in the proteolytic enzyme and buffer solutions at λ = 525 nm. The fluorescence intensity is normalized by the value at 0 min. The rapid decrease in the eGFP fluorescence intensity supports the denaturation and degradation of the protein-based edible codes. The enzymatic tests were repeated four times, and the error bar is a standard deviation. (d) Red blood cell hemolysis test of different silk fibroin solutions. For comparison, 0.1% Triton X-100 and phosphate-buffered saline (PBS) without silk solutions were used as positive (hemolysis efficiency of 100%) and negative (0%) controls, respectively. Inset: representative photograph of samples using sheep erythrocytes.
References
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- 25Newton, P. N.; Bond, K. C.; Countries, S. COVID-19 and risks to the supply and quality of tests, drugs, and vaccines. Lancet Glob. Health 2020, 8, E754– E755, DOI: 10.1016/S2214-109X(20)30136-4There is no corresponding record for this reference.
- 26Schneider, M.; Ho Tu Nam, N. Africa and counterfeit pharmaceuticals in the times of COVID-19. J. Intellect. Prop. Law Pract. 2020, 15, 417– 418, DOI: 10.1093/jiplp/jpaa073There is no corresponding record for this reference.
- 27Moyle, L.; Childs, A.; Coomber, R.; Barratt, M. J. #Drugsforsale: An exploration of the use of social media and encrypted messaging apps to supply and access drugs. Int. J. Drug Policy 2019, 63, 101– 110, DOI: 10.1016/j.drugpo.2018.08.00527https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BB3cngtVOlsg%253D%253D&md5=2d9440eb43b8190c82fc5b50d7024e51#Drugsforsale: An exploration of the use of social media and encrypted messaging apps to supply and access drugsMoyle Leah; Childs Andrew; Coomber Ross; Barratt Monica JThe International journal on drug policy (2019), 63 (), 101-110 ISSN:.BACKGROUND: The use of new technology is frequently harnessed by drug suppliers to both increase profits and reduce risk. While a growing body of research has investigated drug sales through online pharmacies and cryptomarkets, despite growing media interest, no published research exists on how smartphone-enabled social media and messaging applications ('apps') are utilised in the drug economy. This study analyses the ways such apps (e.g. Snapchat, Instagram and WhatsApp) are utilised to supply and access drugs. METHODS: Three data collection methods were employed: an international online survey of 358 drug users that had either used or considered using apps to access drugs; 'rapid' interviews (n = 20) with a similar population; and in-depth interviews (n = 27). Key issues explored were the perceived benefits and risks associated with sourcing drugs through apps, with specific attention paid to novel supply and purchasing practices. RESULTS: Apps appear to provide a quick, convenient method for connecting buyer and seller. They were often viewed as a valuable intermediary option between cryptomarkets and street dealing, providing 'secure' features and the opportunity to preview product without the requirement for technical expertise. Apps are used in a range of novel and diverse ways, including as social networking spaces in which drugs are advertised, and as encrypted messaging services for communicating with known sellers and arranging transactions. Key anxieties related to potential for exposure to law enforcement and legitimacy of substances. CONCLUSION: Though 'social supply' through friends is still typically preferred and there is a degree of wariness toward app-mediated supply, our data indicate that apps are fast becoming a viable option for accessing drugs. Apps can provide an easily accessible platform that connects buyers with commercial drug suppliers and substances that may otherwise remain elusive. Potential harms can be reduced through the provision of information which demystify common-sense assumptions that apps are secure and that this 'visual' drug economy promotes safer purchasing practices.
- 28BeSafeRx: know your online pharmacy, U.S. Food and Drug Administration (FDA), fda.gov/drugs/quick-tips-buying-medicines-over-internet/besaferx-your-source-online-pharmacy-information (Accessed August, 2021).There is no corresponding record for this reference.
- 29Alliance for Safe Online Pharmacies (ASOP) Global; buysaferx.pharmacy, www.buysaferx.pharmacy (Accessed July, 2021).There is no corresponding record for this reference.
- 30Bansal, D.; Malla, S.; Gudala, K.; Tiwari, P. Anti-counterfeit technologies: A pharmaceutical industry perspective. Sci. Pharm. 2013, 81, 1– 13, DOI: 10.3797/scipharm.1202-0330https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXkvVOmu7k%253D&md5=ab35c6b9c117cc33fad018712ab77e05Anti-counterfeit technologies: a pharmaceutical industry perspectiveBansal, Dipika; Malla, Swathi; Gudala, Kapil; Tiwari, PramilScientia Pharmaceutica (2013), 81 (1), 1-13CODEN: SCPHA4; ISSN:0036-8709. (Oesterreichische Apotheker-Verlagsgesellschaft)A review. Growth of international free trade and inadequate drug regulation have led to the expansion of trade in counterfeit drugs worldwide. Technol. protection is seen to be the best way to avoid this problem. Different technologies came into existence like overt, covert, and track and trace technologies. This review emphasizes ideal technol. characteristics, existing anti-counterfeit technologies, and their adoption in different countries. Developed countries like the USA have implemented RFID while the European trend is towards 2D barcodes. The Indian government is getting sensitized about the extent of the problem and has formulated rules mandating barcodes. Even the pharmaceutical companies have been employing these technologies in order to detain illegitimate drugs in their supply chain.
- 31Mackey, T. K.; Nayyar, G. A review of existing and emerging digital technologies to combat the global trade in fake medicines. Expert Opin. Drug Saf. 2017, 16, 587– 602, DOI: 10.1080/14740338.2017.131322731https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC1cvhvVKgsg%253D%253D&md5=8aa7a16679e89cef85ef642b849ff9bcA review of existing and emerging digital technologies to combat the global trade in fake medicinesMackey Tim K; Mackey Tim K; Nayyar Gaurvika; Mackey Tim KExpert opinion on drug safety (2017), 16 (5), 587-602 ISSN:.INTRODUCTION: The globalization of the pharmaceutical supply chain has introduced new challenges, chief among them, fighting the international criminal trade in fake medicines. As the manufacture, supply, and distribution of drugs becomes more complex, so does the need for innovative technology-based solutions to protect patients globally. Areas covered: We conducted a multidisciplinary review of the science/health, information technology, computer science, and general academic literature with the aim of identifying cutting-edge existing and emerging 'digital' solutions to combat fake medicines. Our review identified five distinct categories of technology including mobile, radio frequency identification, advanced computational methods, online verification, and blockchain technology. Expert opinion: Digital fake medicine solutions are unifying platforms that integrate different types of anti-counterfeiting technologies as complementary solutions, improve information sharing and data collection, and are designed to overcome existing barriers of adoption and implementation. Investment in this next generation technology is essential to ensure the future security and integrity of the global drug supply chain.
- 32Bakan, G.; Ayas, S.; Serhatlioglu, M.; Elbuken, C.; Dana, A. Invisible thin-film patterns with strong infrared emission as an optical security feature. Adv. Opt. Mater. 2018, 6, 1800613, DOI: 10.1002/adom.201800613There is no corresponding record for this reference.
- 33Trenfield, S. J.; Xian Tan, H.; Awad, A.; Buanz, A.; Gaisford, S.; Basit, A. W.; Goyanes, A. Track-and-trace: Novel anti-counterfeit measures for 3D printed personalized drug products using smart material inks. Int. J. Pharmaceut. 2019, 567, 118443, DOI: 10.1016/j.ijpharm.2019.06.034There is no corresponding record for this reference.
- 34Ludasi, K.; Jójárt-Laczkovich, O.; Sovány, T.; Hopp, B.; Smausz, T.; Andrásik, A.; Gera, T.; Kovács, Z.; Regdon, G., Jr. Anti-counterfeiting protection, personalized medicines - development of 2D identification methods using laser technology. Int. J. Pharmaceut. 2021, 605, 120793, DOI: 10.1016/j.ijpharm.2021.120793There is no corresponding record for this reference.
- 35Drug Supply Chain Security Act Resources for State Officials, U.S. Food and Drug Administration (FDA), fda.gov/drugs/drug-supply-chain-security-act-dscsa/drug-supply-chain-security-act-resources-state-officials, Accessed: August 2021.There is no corresponding record for this reference.
- 36MediLedger; mediledger.com (Accessed June 2021).There is no corresponding record for this reference.
- 37Fei, J.; Liu, R. Drug-laden 3D biodegradable label using QR code for anti-counterfeiting of drugs. Mater. Sci. Eng. C-Mater. 2016, 63, 657– 662, DOI: 10.1016/j.msec.2016.03.00437https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28XkvVCjt7c%253D&md5=2c322bb3d722436c1d5b726810f2b5b4Drug-laden 3D biodegradable label using QR code for anti-counterfeiting of drugsFei, Jie; Liu, RanMaterials Science & Engineering, C: Materials for Biological Applications (2016), 63 (), 657-662CODEN: MSCEEE; ISSN:0928-4931. (Elsevier B.V.)Wiping out counterfeit drugs is a great task for public health care around the world. The boost of these drugs makes treatment to become potentially harmful or even lethal. In this paper, biodegradable drug-laden QR code label for anti-counterfeiting of drugs is proposed that can provide the non-fluorescence recognition and high capacity. It is fabricated by the laser cutting to achieve the roughness over different surface which causes the difference in the gray levels on the translucent material the QR code pattern, and the micro mold process to obtain the drug-laden biodegradable label. We screened biomaterials presenting the relevant conditions and further requirements of the package. The drug-laden microlabel is on the surface of the troches or the bottom of the capsule and can be read by a simple smartphone QR code reader application. Labeling the pill directly and decoding the information successfully means more convenient and simple operation with non-fluorescence and high capacity in contrast to the traditional methods.
- 38Edinger, M.; Bar-Shalom, D.; Sandler, N.; Rantanen, J.; Genina, N. QR encoded smart oral dosage forms by inkjet printing. Int. J. Pharmaceut. 2018, 536, 138– 145, DOI: 10.1016/j.ijpharm.2017.11.052There is no corresponding record for this reference.
- 39Felicity, T. Securing each dose: Reducing falsification risk with dosage level authentication. Pharmaceut. Technol. 2021, 2021 Supplement, s29– s31There is no corresponding record for this reference.
- 40Altamimi, M. J.; Greenwood, J. C.; Wolff, K.; Hogan, M. E.; Lakhani, A.; Martin, G. P.; Royall, P. G. Anti-counterfeiting DNA molecular tagging of pharmaceutical excipients: An evaluation of lactose containing tablets. Int. J. Pharmaceut. 2019, 571, 118656, DOI: 10.1016/j.ijpharm.2019.118656There is no corresponding record for this reference.
- 41Ilko, D.; Steiger, C.; Keller, R.; Holzgrabe, U.; Meinel, L. Tamper-proof tablets for distinction between counterfeit and originator drugs through PEG coding. Eur. J. Pharm. Biopharm. 2016, 99, 1– 6, DOI: 10.1016/j.ejpb.2015.11.00941https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXhvFCqtbjM&md5=c654a60ab0504ce3536689e3340807a9Tamper-proof tablets for distinction between counterfeit and originator drugs through PEG codingIlko, David; Steiger, Christoph; Keller, Rupprecht; Holzgrabe, Ulrike; Meinel, LorenzEuropean Journal of Pharmaceutics and Biopharmaceutics (2016), 99 (), 1-6CODEN: EJPBEL; ISSN:0939-6411. (Elsevier B.V.)Counterfeit drugs are a major threat to public health. Current efforts focus on serialization of the secondary packaging which do not allow to trace the individual unit. As a proof of concept, we intended to mark each tablet for its unambiguous recognition. Spiking monodisperse PEGs into tablet coating solns. at concns. as low as 3 ppm was instrumental to "write" a code into each tablet film which was readily read upon isolation and LC-MS/MS anal. Different qualities and amts. of monodisperse polyethylene glycols can be used for coding solid drug products. The approach is limited to cases in which PEGs are not present for formulation purposes as excipients, as coding against this background was unfeasible.
- 42Felton, L. A.; Shah, P. P.; Sharp, Z.; Atudorei, V.; Timmins, G. S. Stable isotope-labeled excipients for drug product identification and counterfeit detection. Drug Dev. Ind. Pharm. 2011, 37, 88– 92, DOI: 10.3109/03639045.2010.49239742https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3cXhsFamu7zJ&md5=42d705c51e8adf72285feaa7839da183Stable isotope-labeled excipients for drug product identification and counterfeit detectionFelton, Linda A.; Shah, Punit P.; Sharp, Zachary; Atudorei, Viorel; Timmins, Graham S.Drug Development and Industrial Pharmacy (2011), 37 (1), 88-92CODEN: DDIPD8; ISSN:0363-9045. (Informa Healthcare)Counterfeit drug products have become a major problem worldwide and a no. of techniques to detect counterfeit products or reduce the potential for counterfeiting were investigated. This study examd. the use of stable isotope-labeled excipients in solid dosage forms as a method to identify drug products and to detect counterfeits. 2H- and 13C-glucose were used as model excipients and incorporated in wet granulated formulations at a variety of different isotopic ratios. The ratios of 2H/1H and 13C/12C in each product were then detd. by isotope ratio mass spectrometry. Results demonstrated the ability to detect the isotope-labeled glucose in both granules and tablets. It was possible to use the isotope ratios to differentiate between specific batches of granules, demonstrating the potential of this technique for in-product, batch-specific identification.
- 43Grover, W. H. Candycodes: Simple universally unique edible identifiers for confirming the authenticity of pharmaceuticals. medRxiv 2021, DOI: 10.1101/2021.07.30.21261395 .There is no corresponding record for this reference.
- 44Jeon, H. J.; Leem, J. W.; Ji, Y.; Park, S. M.; Park, J.; Kim, K. Y.; Kim, S. W.; Kim, Y. L. Cyber-physical watermarking with inkjet edible bioprinting. Adv. Funct. Mater. 2022, 2112479, DOI: 10.1002/adfm.20211247944https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB38XisFGisrw%253D&md5=72ec37dbb25ba1b5d6ff334f10accd40Cyber-Physical Watermarking with Inkjet Edible BioprintingJeon, Hee-Jae; Leem, Jung Woo; Ji, Yuhyun; Park, Sang Mok; Park, Jongwoo; Kim, Kee-Young; Kim, Seong-Wan; Kim, Young L.Advanced Functional Materials (2022), 32 (18), 2112479CODEN: AFMDC6; ISSN:1616-301X. (Wiley-VCH Verlag GmbH & Co. KGaA)Counterfeit medicines are a fundamental healthcare problem, threatening patient safety and public health as well as causing economic damage. Online pharmacies and the ongoing pandemic have promoted medicine counterfeiting. However, the existing anticounterfeit methods are limited because of material toxicity, low security, and complicated fabrication. Here a dosage-level security method is introduced that combines digital watermarking and phys. printing at the material level. A set of requirements is designed to ensure the edibility, printability, imperceptibility, and robustness of cyber-phys. watermarking. An inkjet printer using safe food coloring is adapted to print a watermarked image on a recombinant luminescent silk protein taggant to enhance attack resistance. Machine learning of color accuracy recovers unavoidable color distortions during printing and acquisition, allowing robust smartphone readability. An edible watermarked taggant affixed to each individual medicine can offer anticounterfeit and authentication features at the dosage level, empowering every patient to aid in abating illicit medicines.
- 45Fukuoka, T.; Yamaguchi, A.; Hara, R.; Matsumoto, T.; Utsumi, Y.; Mori, Y. Application of gold nanoparticle self-assemblies to unclonable anti-counterfeiting technology. In 2015 International Conference on Electronic Packaging and Imaps All Asia Conference (ICEP-IAAC) , Piscataway, New Jersey, USA, 2015, pp 432– 435.There is no corresponding record for this reference.
- 46Smith, J. D.; Reza, M. A.; Smith, N. L.; Gu, J. X.; Ibrar, M.; Crandall, D. J.; Skrabalak, S. E. Plasmonic anticounterfeit tags with high encoding capacity rapidly authenticated with deep machine learning. ACS Nano 2021, 15, 2901– 2910, DOI: 10.1021/acsnano.0c0897446https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3MXjsFSrur4%253D&md5=1a8b0686a503227b1d57c8ba79b4e0abPlasmonic Anticounterfeit Tags with High Encoding Capacity Rapidly Authenticated with Deep Machine LearningSmith, Joshua D.; Reza, Md Alimoor; Smith, Nathanael L.; Gu, Jianxin; Ibrar, Maha; Crandall, David J.; Skrabalak, Sara E.ACS Nano (2021), 15 (2), 2901-2910CODEN: ANCAC3; ISSN:1936-0851. (American Chemical Society)Counterfeit goods create significant economic losses and product failures in many industries. Here, we report a covert anticounterfeit platform where plasmonic nanoparticles (NPs) create phys. unclonable functions (PUFs) with high encoding capacity. By allowing anisotropic Au NPs of different sizes to deposit randomly, a diversity of surfaces can be facilely tagged with NP deposits that serve as PUFs and are analyzed using optical microscopy. High encoding capacity is engineered into the tags by the sizes of the Au NPs, which provide a range of color responses, while their anisotropy provides sensitivity to light polarization. An estd. encoding capacity of 270n is achieved, which is one of the highest reported to date. Authentication of the tags with deep machine learning allows for high accuracy and rapid matching of a tag to a specific product. Moreover, the tags contain descriptive metadata that is leveraged to match a tag to a specific lot no. (i.e., a collection of tags created in the same manner from the same formulation of anisotropic Au NPs). Overall, integration of designer plasmonic NPs with deep machine learning methods can create a rapidly authenticated anticounterfeit platform with high encoding capacity.
- 47Smith, A. F.; Skrabalak, S. E. Metal nanomaterials for optical anti-counterfeit labels. J. Mater. Chem. C 2017, 5, 3207– 3215, DOI: 10.1039/C7TC00080D47https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXksVCqsr8%253D&md5=3a74db3c36cd72e4d088f84c828006dfMetal nanomaterials for optical anti-counterfeit labelsSmith, Alison F.; Skrabalak, Sara E.Journal of Materials Chemistry C: Materials for Optical and Electronic Devices (2017), 5 (13), 3207-3215CODEN: JMCCCX; ISSN:2050-7534. (Royal Society of Chemistry)The global economic, security, and health challenges presented by counterfeit goods require new approaches toward anti-counterfeit labels. This review describes recent advances in the use of metal nanomaterials for optical anti-counterfeit labels that may offer a multiplexed approach to security tags that can be easily fabricated, offer large coding capacity, and be interrogated throughout the supply chain and by the end user. This review also critically discusses the current approach to developing continuously more complex labels and offers awareness toward the need for simple, yet unclonable, taggants.
- 48Ji, X. F.; Wu, R. T.; Long, L. L.; Ke, X. S.; Guo, C. X.; Ghang, Y. J.; Lynch, V. M.; Huang, F. H.; Sessler, J. L. Encoding, reading, and transforming information using multifluorescent supramolecular polymeric hydrogels. Adv. Mater. 2018, 30, 1705480, DOI: 10.1002/adma.201705480There is no corresponding record for this reference.
- 49Li, Z. Q.; Chen, H. Z.; Li, B.; Xie, Y. M.; Gong, X. L.; Liu, X.; Li, H. R.; Zhao, Y. L. Photoresponsive luminescent polymeric hydrogels for reversible information encryption and decryption. Adv. Sci. 2019, 6, 1901529, DOI: 10.1002/advs.20190152949https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1MXisVWqtrjF&md5=3c34ef647f19af747f03d8c7350a9529Photoresponsive Luminescent Polymeric Hydrogels for Reversible Information Encryption and DecryptionLi, Zhiqiang; Chen, Hongzhong; Li, Bin; Xie, Yanmiao; Gong, Xiaoli; Liu, Xiao; Li, Huanrong; Zhao, YanliAdvanced Science (Weinheim, Germany) (2019), 6 (21), 1901529CODEN: ASDCCF; ISSN:2198-3844. (Wiley-VCH Verlag GmbH & Co. KGaA)Conventional luminescent information is usually visible under either ambient or UV light, hampering their potential application in smart confidential information protection. In order to address this challenge, herein, light-triggered luminescence ON-OFF switchable hybrid hydrogels are successfully constructed through in situ copolymn. of acrylamide, lanthanide complex, and diarylethene photochromic unit. The open-close behavior of the diarylethene ring in the polymer could be controlled by UV and visible light irradn., where the close form of the ring features fluorescence resonance energy transfer with the lanthanide complex. The hydrogel-based blocks with tunable emission colors are then employed to construct 3D information codes, which can be read out under a 254 nm UV lamp. The exposure to 300 nm UV light leads to the luminescence quenching of the hydrogels, thus erasing the encoded information. Under visible light (>450 nm) irradn., the luminescence is recovered to make the confidential information readable again. Thus, by simply alternating the exposure to UV and visible lights, the luminescence signals could become invisible and visible reversibly, allowing for reversible multiple information encryption and decryption.
- 50Liu, F.; Nattestad, A.; Naficy, S.; Han, R.; Casillas, G.; Angeloski, A.; Sun, X.; Huang, Z. Fluorescent carbon- and oxygen-doped hexagonal boron nitride powders as printing ink for anticounterfeit applications. Adv. Opt. Mater. 2019, 7, 1901380, DOI: 10.1002/adom.20190138050https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1MXhvVemsr%252FI&md5=1f383bb96e108fe31d54b5a346a15d01Fluorescent Carbon- and Oxygen-Doped Hexagonal Boron Nitride Powders as Printing Ink for Anticounterfeit ApplicationsLiu, Feng; Nattestad, Andrew; Naficy, Sina; Han, Rui; Casillas, Gilberto; Angeloski, Alexander; Sun, Xudong; Huang, ZhenguoAdvanced Optical Materials (2019), 7 (24), 1901380CODEN: AOMDAX; ISSN:2195-1071. (Wiley-VCH Verlag GmbH & Co. KGaA)Increasing demands for optical anticounterfeiting technol. require the development of versatile luminescent materials with tunable photoluminescence properties. Herein, a no. of fluorescent carbon- and oxygen-doped hexagonal boron nitride (denoted as BCNO) phosphors are found to offer a such high-tech anticounterfeiting soln. These multicolor BCNO powders, developed in a two-step process with controlled annealing and oxidn., feature rod-like particle shape, with varied luminescence properties. Studies of the optical properties of BCNO, along with other characterization, provide insight into this underexplored material. Anticounterfeiting applications are demonstrated with printed patterns which are indistinguishable to the naked eye under visible light but become highly discernible under UV irradn. The fabricated patterns are demonstrated to be both chem. stable in corrosive environments and phys. robust in mech. bending testing. These properties render BCNO as promising and versatile anticounterfeiting material a wide variety of environments.
- 51Abdollahi, A.; Roghani-Mamaqani, H.; Razavi, B.; Salami-Kalajahi, M. Photoluminescent and chromic nanomaterials for anticounterfeiting technologies: Recent advances and future challenges. ACS Nano 2020, 14, 14417– 14492, DOI: 10.1021/acsnano.0c0728951https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXitV2ntrrK&md5=8cc3c9b883c9888f64fdd5d9c8bd92bfPhotoluminescent and Chromic Nanomaterials for Anticounterfeiting Technologies: Recent Advances and Future ChallengesAbdollahi, Amin; Roghani-Mamaqani, Hossein; Razavi, Bahareh; Salami-Kalajahi, MehdiACS Nano (2020), 14 (11), 14417-14492CODEN: ANCAC3; ISSN:1936-0851. (American Chemical Society)A review. Counterfeiting and inverse engineering of security and confidential documents, such as banknotes, passports, national cards, certificates, and valuable products, has significantly been increased, which is a major challenge for governments, companies, and customers. From recent global reports published in 2017, the counterfeiting market was evaluated to be $107.26 billion in 2016 and forecasted to reach $206.57 billion by 2021 at a compd. annual growth rate of 14.0%. Development of anticounterfeiting and authentication technologies with multilevel securities is a powerful soln. to overcome this challenge. Stimuli-chromic (photochromic, hydrochromic, and thermochromic) and photoluminescent (fluorescent and phosphorescent) compds. are the most significant and applicable materials for development of complex anticounterfeiting inks with a high-security level and fast authentication. Highly efficient anticounterfeiting and authentication technologies have been developed to reach high security and efficiency. Applicable materials for anticounterfeiting applications are generally based on photochromic and photoluminescent compds., for which hydrochromic and thermochromic materials have extensively been used in recent decades. A wide range of materials, such as org. and inorg. metal complexes, polymer nanoparticles, quantum dots, polymer dots, carbon dots, upconverting nanoparticles, and supramol. structures, could display all of these phenomena depending on their phys. and chem. characteristics. The polymeric anticounterfeiting inks have recently received significant attention because of their high stability for printing on confidential documents. In addn., the printing technologies including hand-writing, stamping, inkjet printing, screen printing, and anticounterfeiting labels are discussed for introduction of the most efficient methods for application of different anticounterfeiting inks. This review would help scientists to design and develop the most applicable encryption, authentication, and anticounterfeiting technologies with high security, fast detection, and potential applications in security marking and information encryption on various substrates.
- 52Wang, H.; Ji, X. F.; Page, Z. A.; Sessler, J. L. Fluorescent materials-based information storage. Mater. Chem. Front. 2020, 4, 1024– 1039, DOI: 10.1039/C9QM00607A52https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1MXit1Srsb7P&md5=80572fc16763a263ce2f370cbbaf7243Fluorescent materials-based information storageWang, Hu; Ji, Xiaofan; Page, Zachariah A.; Sessler, Jonathan L.Materials Chemistry Frontiers (2020), 4 (4), 1024-1039CODEN: MCFAC5; ISSN:2052-1537. (Royal Society of Chemistry)The third industrial revolution has brought mankind into the information age. The development of information storage materials has played a key role in this transformation. Such materials have seen use in many application areas, including computing, logistics, and medicine. Information storage materials run the gamut from magnetic information storage media to mol.-based information storage materials. Among these, fluorescent-based information storage materials are of particular interest due to their unique properties, including an ability to store information with high levels of security, maintain mech. stability, and respond to appropriately chosen external stimuli. In this review, we focus on recent advances involving the prepn. and study of fluorescent materials-based information storage codes. For organisational purposes, these codes are treated according to the dimensionality of the code system in question, namely 1D-, 2D-, and 3D-type codes. The present review is designed to provide a succinct summary of what has been accomplished in the area, while outlining existing challenges and noting directions for future development.
- 53Zhuang, Y. L.; Ren, X. L.; Che, X. T.; Liu, S. J.; Huang, W.; Zhao, Q. Organic photoresponsive materials for information storage: A review. Adv. Photonics 2021, 3, 014001, DOI: 10.1117/1.AP.3.1.014001There is no corresponding record for this reference.
- 54Tan, J.; Li, Q. J.; Meng, S.; Li, Y. C.; Yang, J.; Ye, Y. X.; Tang, Z. K.; Qu, S. N.; Ren, X. D. Time-dependent phosphorescence colors from carbon dots for advanced dynamic information encryption. Adv. Mater. 2021, 33, 2006781, DOI: 10.1002/adma.20200678154https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3MXmsVCrsLo%253D&md5=a27618fcd63a17eb22dbc79f810dc7c3Time-Dependent Phosphorescence Colors from Carbon Dots for Advanced Dynamic Information EncryptionTan, Jing; Li, Qijun; Meng, Shuai; Li, Yuchen; Yang, Jian; Ye, Yunxia; Tang, Zikang; Qu, Songnan; Ren, XudongAdvanced Materials (Weinheim, Germany) (2021), 33 (16), 2006781CODEN: ADVMEW; ISSN:0935-9648. (Wiley-VCH Verlag GmbH & Co. KGaA)The development of phosphorescent materials with time-dependent phosphorescence colors (TDPCs) is of considerable interest for application in advanced dynamic information encryption. In this study, TDPC is realized in carbon dots (CDs) synthesized by the one-pot hydrothermal treatment of levofloxacin. CD ink printed on paper (CD@paper) exhibits a change in phosphorescence color from orange to green, 1 s after irradn. with 395 nm light. However, when irradiated with wavelengths shorter or longer than 395 nm, the CD@paper exhibits only green or red phosphorescence, resp. The red and green phosphorescence originates from the low-energy surface oxide triplet state and high-energy N-related triplet state, resp. When irradiated with a suitable light energy (around 395 nm wavelength), the two phosphorescent centers can be simultaneously activated, emitting red and green phosphorescence with different decay rates. The red and green phosphorescence merge into an orange phosphorescence initially, exhibiting the TDPC phenomenon. Based on the unusual phosphorescent properties of the CDs, a kind of multilevel, dynamic phosphorescence colored 3D code is designed for advanced dynamic information encryption.
- 55Yang, Y. B.; Li, Q. Y.; Zhang, H. W.; Liu, H.; Ji, X. F.; Tang, B. Z. Codes in code: Aie supramolecular adhesive hydrogels store huge amounts of information. Adv. Mater. 2021, 33, 2105418, DOI: 10.1002/adma.20210541855https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3MXitFagsbzO&md5=68dc444bf66d5293101d416450f0e93fCodes in Code: AIE supramolecular adhesive hydrogels store huge amounts of informationYang, Yabi; Li, Qingyun; Zhang, Hanwei; Liu, Hui; Ji, Xiaofan; Tang, Ben ZhongAdvanced Materials (Weinheim, Germany) (2021), 33 (45), 2105418CODEN: ADVMEW; ISSN:0935-9648. (Wiley-VCH Verlag GmbH & Co. KGaA)With the continuous advancement of information technol., the requirements for the information storage capacity of materials are getting higher and higher. However, information code materials usually only store a single piece of information. In order to improve their storage capacity, aggregation-induced emission (AIE) supramol. adhesive hydrogels with different fluorescent colors are prepd., and a "Codes in Code" method is used to demonstrate the storage capacity for large amts. of information. Four kinds of poly(vinyl alc.) (PVA) supramol. hydrogels with different fluorescent colors are prepd.; based on the hydrogen bonds on the hydrogel surface, these hydrogels can be assembled into a hydrogel, G5, which shows multiple fluorescent colors under the irradn. of UV light. When many 1D barcode patterns or/and 2D code patterns are incorporated into G5, not only a kind of 3D information but also plenty of 1D or/and 2D information can be stored. Therefore, the information codes prepd. by the "Codes in Code" method can store a large amt. of information.
- 56Li, Z. Q.; Liu, X.; Wang, G. N.; Li, B.; Chen, H. Z.; Li, H. R.; Zhao, Y. L. Photoresponsive supramolecular coordination polyelectrolyte as smart anticounterfeiting inks. Nat. Commun. 2021, 12, 1363, DOI: 10.1038/s41467-021-21677-456https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3MXltl2gtLc%253D&md5=ddf344ad755b81b89370a68c2e090a2cPhotoresponsive supramolecular coordination polyelectrolyte as smart anticounterfeiting inksLi, Zhiqiang; Liu, Xiao; Wang, Guannan; Li, Bin; Chen, Hongzhong; Li, Huanrong; Zhao, YanliNature Communications (2021), 12 (1), 1363CODEN: NCAOBW; ISSN:2041-1723. (Nature Research)While photoluminescence printing is a widely applied anticounterfeiting technique, there are still challenges in developing new generation anticounterfeiting materials with high security. Here we report the construction of a photoresponsive supramol. coordination polyelectrolyte (SCP) through hierarchical self-assembly of lanthanide ion, bis-ligand and diarylethene unit, driven by metal-ligand coordination and ionic interaction. Owing to the conformation-dependent photochromic fluorescence resonance energy transfer between the lanthanide donor and diarylethene acceptor, the ring-closure/ring-opening isomerization of the diarylethene unit leads to a photoreversible luminescence on/off switch in the SCP. The SCP is then utilized as security ink to print various patterns, through which photoreversible multiple information patterns with visible/invisible transformations are realized by simply alternating the irradn. with UV and visible light. This work demonstrates the possibility of developing a new class of smart anticounterfeiting materials, which could be operated in a noninvasive manner with a higher level of security.
- 57Zhang, H. W.; Li, Q. Y.; Yang, Y. B.; Ji, X. F.; Sessler, J. L. Unlocking chemically encrypted information using three types of external stimuli. J. Am. Chem. Soc. 2021, 143, 18635– 18642, DOI: 10.1021/jacs.1c0855857https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3MXitlCrtb3L&md5=5d580be4c3c406431b020b6a9aa98f0bUnlocking Chemically Encrypted Information columnarUsing Three Types of External StimuliZhang, Hanwei; Li, Qingyun; Yang, Yabi; Ji, Xiaofan; Sessler, Jonathan L.Journal of the American Chemical Society (2021), 143 (44), 18635-18642CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)Encryption is crit. to information security; however, existing chem.-based information encryption strategies are still in their infancy. We report here a new approach to chem. encryption involving a supramol. gel QR (quick response) code with multiple encryption functions. Three color "turn-on" supramol. polymer gels, G1-G3, were prepd. that produce pink, purple, and yellow colors when subject to treatment with acetic acid vapor, UV light, and methanolic FeCl3, resp. As the result of hydrogen-bonding interactions at the gel interfaces, the three gels can be assembled to produce gel G4. Engraving a QR code pattern onto G4 then gave gel G5. When one or two stimuli are applied to the individual pieces corresponding to the QR engraved versions of the gels G1-G3 making up G5, a complete scannable pattern is not displayed, and the stored information cannot be recognized. Only when three different stimuli are applied at the same time does G5 give a complete recognizable pattern allowing the stored information to be retrieved. This strategy was applied to the decryption-based opening of a coded lock.
- 58Zhang, H. Y.; Hua, D. W.; Huang, C. B.; Samal, S. K.; Xiong, R. H.; Sauvage, F.; Braeckmans, K.; Remaut, K.; De Smedt, S. C. Materials and technologies to combat counterfeiting of pharmaceuticals: Current and future problem tackling. Adv. Mater. 2020, 32, 1905486, DOI: 10.1002/adma.20190548658https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXitFCiurg%253D&md5=9b0dd4aa31d6e0c1630e8e9678330c14Materials and technologies to combat counterfeiting of pharmaceuticals: Current and future problem tacklingZhang, Heyang; Hua, Dawei; Huang, Chaobo; Samal, Sangram Keshari; Xiong, Ranhua; Sauvage, Felix; Braeckmans, Kevin; Remaut, Katrien; De Smedt, Stefaan C.Advanced Materials (Weinheim, Germany) (2020), 32 (11), 1905486CODEN: ADVMEW; ISSN:0935-9648. (Wiley-VCH Verlag GmbH & Co. KGaA)A review. The globalization of drug trade leads to the expansion of pharmaceutical counterfeiting. The immense threat of low quality drugs to millions of patients is considered to be an under-addressed global health challenge. Anal. authentication technologies are the most effective methods to identify active pharmaceutical ingredients and impurities. However, most of these anal. testing techniques are expensive and need skilled personnel. To combat counterfeiting of drugs, the package of an increasing no. of drugs is being protected through advanced package labeling technologies. Though, package labeling is only effective if the drugs are not repackaged. Therefore "in-drug labeling," instead of "drug package labeling," may become powerful tools to protect drugs. This review aims to overview how advanced micro- and nanomaterials might become interesting markers for the labeling of tablets and capsules. Clearly, how well such identifiers can be integrated into "solid drugs" without compromising drug safety and efficacy remains a challenge. Also, incorporation of tags has so far only been reported for the protection of solid drug dosage forms. No doubts that in-drug labeling technologies for "liq. drugs," like injectables which contain expensive peptides, monoclonal antibodies, vaccines, dermal fillers, could help to protect them from counterfeiting as well.
- 59Huang, C. B.; Lucas, B.; Vervaet, C.; Braeckmans, K.; Van Calenbergh, S.; Karalic, I.; Vandewoestyne, M.; Deforce, D.; Demeester, J.; De Smedt, S. C. Unbreakable codes in electrospun fibers: Digitally encoded polymers to stop medicine counterfeiting. Adv. Mater. 2010, 22, 2657– 2661, DOI: 10.1002/adma.20100013059https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3cXosVGht7o%253D&md5=139ae432193b9e2df317489f6e307007Unbreakable Codes in Electrospun Fibers: Digitally Encoded Polymers to Stop Medicine CounterfeitingHuang, Chaobo; Lucas, Bart; Vervaet, Chris; Braeckmans, Kevin; Van Calenbergh, Serge; Karalic, Izet; Vandewoestyne, Mado; Deforce, Dieter; Demeester, Jo; De Smedt, Stefaan C.Advanced Materials (Weinheim, Germany) (2010), 22 (24), 2657-2662CODEN: ADVMEW; ISSN:0935-9648. (Wiley-VCH Verlag GmbH & Co. KGaA)A review. Health organizations claim that there should be "zero tolerance" for counterfeit medicines, yet the problem is growing world-wide. Labeling the tablet itself("one-dose marking"), instead of package labeling, could be a powerful strategy to protect patients from fake drugs. Unfortunately this methods are not in use today. This report proposes viable soln.: digitally encode polymers, which already form a major class of pharmaceutical excipients, and place them within tablets.
- 60Han, S.; Bae, H. J.; Kim, J.; Shin, S.; Choi, S. E.; Lee, S. H.; Kwon, S.; Park, W. Lithographically encoded polymer microtaggant using high-capacity and error-correctable QR code for anti-counterfeiting of drugs. Adv. Mater. 2012, 24, 5924– 5929, DOI: 10.1002/adma.20120148660https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC38Xht1Kitb%252FK&md5=da9342e6c8a31308910e9595c3e62e6fLithographically Encoded Polymer Microtaggant Using High-Capacity and Error-Correctable QR Code for Anti-Counterfeiting of DrugsHan, Sangkwon; Bae, Hyung Jong; Kim, Junhoi; Shin, Sunghwan; Choi, Sung-Eun; Lee, Sung Hoon; Kwon, Sunghoon; Park, WookAdvanced Materials (Weinheim, Germany) (2012), 24 (44), 5924-5929CODEN: ADVMEW; ISSN:0935-9648. (Wiley-VCH Verlag GmbH & Co. KGaA)Recently, the incorporation of microtaggants i n drug formulation has been introduced as superior on dose authentication technol. for the anticounterfeiting of drugs. Storing information or data on the microtaggant provides the multifunctionality needed for the identification and track-and-trace monitoring of drugs. Here, we propose a Quick Response (QR)-coded microtaggant that allows the encoding of a large amt. of data that will not be lost during the drug formulation process. In this work, QR-coded polymeric microtaggants were fabricated lithog. through a single exposure to QR Code-patterned UV light in the microfluidic channel. These microtaggants offer all t h e unique features of QR Code, such as highcapacity encoding, error correction capability, and omnidirectional reading. We also demonstrated the complete process of drug authentication using QR-coded microtaggants, from the formulation of the microtaggant-equipped capsule to the decoding step using a QR Code reader application on a smartphone.
- 61You, M. L.; Lin, M.; Wang, S. R.; Wang, X. M.; Zhang, G.; Hong, Y.; Dong, Y. Q.; Jin, G. R.; Xu, F. Three-dimensional quick response code based on inkjet printing of upconversion fluorescent nanoparticles for drug anti-counterfeiting. Nanoscale 2016, 8, 10096– 10104, DOI: 10.1039/C6NR01353H61https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28Xms1Wgsbo%253D&md5=7b434397603f5efaf4de57264c245433Three-dimensional quick response code based on inkjet printing of upconversion fluorescent nanoparticles for drug anti-counterfeitingYou, Minli; Lin, Min; Wang, Shurui; Wang, Xuemin; Zhang, Ge; Hong, Yuan; Dong, Yuqing; Jin, Guorui; Xu, FengNanoscale (2016), 8 (19), 10096-10104CODEN: NANOHL; ISSN:2040-3372. (Royal Society of Chemistry)Medicine counterfeiting is a serious issue worldwide, involving potentially devastating health repercussions. Advanced anti-counterfeit technol. for drugs has therefore aroused intensive interest. However, existing anti-counterfeit technologies are assocd. with drawbacks such as the high cost, complex fabrication process, sophisticated operation and incapability in authenticating drug ingredients. In this contribution, we developed a smart phone recognition based upconversion fluorescent three-dimensional (3D) quick response (QR) code for tracking and anti-counterfeiting of drugs. We firstly formulated three colored inks incorporating upconversion nanoparticles with RGB (i.e., red, green and blue) emission colors. Using a modified inkjet printer, we printed a series of colors by precisely regulating the overlap of these three inks. Meanwhile, we developed a multilayer printing and splitting technol., which significantly increases the information storage capacity per unit area. As an example, we directly printed the upconversion fluorescent 3D QR code on the surface of drug capsules. The 3D QR code consisted of three different color layers with each layer encoded by information of different aspects of the drug. A smart phone APP was designed to decode the multicolor 3D QR code, providing the authenticity and related information of drugs. The developed technol. possesses merits in terms of low cost, ease of operation, high throughput and high information capacity, thus holds great potential for drug anti-counterfeiting.
- 62Rehor, I.; van Vreeswijk, S.; Vermonden, T.; Hennink, W. E.; Kegel, W. K.; Eral, H. B. Biodegradable microparticles for simultaneous detection of counterfeit and deteriorated edible products. Small 2017, 13, 1701804, DOI: 10.1002/smll.201701804There is no corresponding record for this reference.
- 63Liu, R. R.; Jing, J. B.; Zhang, S.; Wang, K.; Xu, B.; Tian, W. J.; Yang, P. Aggregation-induced emission of a 2d protein supramolecular nanofilm with emergent functions. Mater. Chem. Front. 2020, 4, 1256– 1267, DOI: 10.1039/D0QM00031K63https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXktVKitrY%253D&md5=9d136d27e94e1f899693ea4289c6007dAggregation-induced emission of a 2D protein supramolecular nanofilm with emergent functionsLiu, Ruirui; Jing, Jiangbo; Zhang, Song; Wang, Ke; Xu, Bin; Tian, Wenjing; Yang, PengMaterials Chemistry Frontiers (2020), 4 (4), 1256-1267CODEN: MCFAC5; ISSN:2052-1537. (Royal Society of Chemistry)Aggregation-induced emission (AIE) of a 2D protein supramol. nanofilm exhibiting multiple functions is achieved for the first time at the air/water interface or on a solid surface at a timescale of several minutes. The mixt. of lysozyme, tris(2-carboxyethyl)phosphine (TCEP) and 9,10-distyrylanthracene with two ammonium groups (DSAI) results in the rapid synthesis of a phase-transited lysozyme (PTL) AIE nanofilm, coating or ink from a neutral aq. soln. at room temp. The multifunctionality of these waterborne biocompatible DSAI@PTL AIE materials shows some potential applications such as anti-bacterial and anti-counterfeiting for edible items or living creatures. This strategy combines the advantages of AIE with a 2D biopolymer suprastructure and provides an eco-friendly interfacial material with biol. functions and applications. By introducing versatile AIE mols. with different functions and emission, the development of optically active biomimic materials with a wide range of applications could be opened up, such as multi-color polymer coatings.
- 64De Jong, W. H.; Borm, P. J. A. Drug delivery and nanoparticles: Applications and hazards. Int. J. Nanomed. 2008, 3, 133– 149, DOI: 10.2147/IJN.S59664https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1cXps1Wjt7w%253D&md5=db515c60ea3c5b6596b8802e82594c34Drug delivery and nanoparticles: applications and hazardsDe Jong, Wim H.; Borm, Paul J. A.International Journal of Nanomedicine (2008), 3 (2), 133-149CODEN: IJNNHQ; ISSN:1176-9114. (Dove Medical Press (NZ) Ltd.)A review. The use of nanotechnol. in medicine and more specifically drug delivery is set to spread rapidly. Currently many substances are under investigation for drug delivery and more specifically for cancer therapy. Interestingly pharmaceutical sciences are using nanoparticles to reduce toxicity and side effects of drugs and up to recently did not realize that carrier systems themselves may impose risks to the patient. The kind of hazards that are introduced by using nanoparticles for drug delivery are beyond that posed by conventional hazards imposed by chems. in classical delivery matrixes. For nanoparticles the knowledge on particle toxicity as obtained in inhalation toxicity shows the way how to investigate the potential hazards of nanoparticles. The toxicol. of particulate matter differs from toxicol. of substances as the composing chem.(s) may or may not be sol. in biol. matrixes, thus influencing greatly the potential exposure of various internal organs. This may vary from a rather high local exposure in the lungs and a low or neglectable exposure for other organ systems after inhalation. However, absorbed species may also influence the potential toxicity of the inhaled particles. For nanoparticles the situation is different as their size opens the potential for crossing the various biol. barriers within the body. From a pos. viewpoint, esp. the potential to cross the blood brain barrier may open new ways for drug delivery into the brain. In addn., the nanosize also allows for access into the cell and various cellular compartments including the nucleus. A multitude of substances are currently under investigation for the prepn. of nanoparticles for drug delivery, varying from biol. substances like albumin, gelatine and phospholipids for liposomes, and more substances of a chem. nature like various polymers and solid metal contg. nanoparticles. It is obvious that the potential interaction with tissues and cells, and the potential toxicity, greatly depends on the actual compn. of the nanoparticle formulation. This paper provides an overview on some of the currently used systems for drug delivery. Besides the potential beneficial use also attention is drawn to the questions how we should proceed with the safety evaluation of the nanoparticle formulations for drug delivery. For such testing the lessons learned from particle toxicity as applied in inhalation toxicol. may be of use. Although for pharmaceutical use the current requirements seem to be adequate to detect most of the adverse effects of nanoparticle formulations, it can not be expected that all aspects of nanoparticle toxicol. will be detected. So, probably addnl. more specific testing would be needed.
- 65Kumar, A.; Dhawan, A. Genotoxic and carcinogenic potential of engineered nanoparticles: An update. Arch. Toxicol. 2013, 87, 1883– 1900, DOI: 10.1007/s00204-013-1128-z65https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXhsFSkur%252FJ&md5=38e02c03bb62d2efc611d8bbcc35f174Genotoxic and carcinogenic potential of engineered nanoparticles: an updateKumar, Ashutosh; Dhawan, AlokArchives of Toxicology (2013), 87 (11), 1883-1900CODEN: ARTODN; ISSN:0340-5761. (Springer)A review. Nanoscience and nanotechnol. have seen an exponential growth over the past decade largely due to the unique properties of engineered nanoparticles (ENPs), advances in ENP synthesis, and imaging or anal. tools. The unique properties such as high surface area to vol. ratio, abundant reactive sites on the surface, large fraction of atoms located on the exterior face have made these novel materials the most sought after for consumer and industrial applications. This significant increase in the ENP contg. consumer products has also enhanced the chances of human and environmental exposure. Humans get exposed to ENPs at various steps of its synthesis (lab.), manuf. (industry), use (consumer products, devices, medicines, etc.) and through the environment (contaminated water, aerosolized particles, and disposal). Such exposures to ENPs are known to induce genotoxicity, cytotoxicity, and carcinogenicity in biol. system. This is attributed to several factors, such as direct interaction of ENPs with the genetic material, indirect damage due to reactive oxygen species generation, release of toxic ions from sol. ENPs, interaction with cytoplasmic/nuclear proteins, binding with mitotic spindle or its components, increased oxidative stress, disturbance of cell cycle checkpoint functions, inhibition of antioxidant defense, and many others. The present review describes an overview of in vitro and in vivo genotoxicity studies with ENPs, advantages and potential problems assocd. with the methods used in genotoxicity assessment, and the need for appropriate method and approach for risk assessment of ENPs.
- 66Trasande, L.; Liu, B. Y.; Bao, W. Phthalates and attributable mortality: A population-based longitudinal cohort study and cost analysis. Environ. Pollut. 2022, 292, 118021, DOI: 10.1016/j.envpol.2021.11802166https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3MXit1alu7bO&md5=743d42a2fb25ffb4577b064458cb0169Phthalates and attributable mortality: A population-based longitudinal cohort study and cost analysisTrasande, Leonardo; Liu, Buyun; Bao, WeiEnvironmental Pollution (Oxford, United Kingdom) (2022), 292 (Part_A), 118021CODEN: ENPOEK; ISSN:0269-7491. (Elsevier Ltd.)Accelerating evidence of endocrine-related morbidity has raised alarm about the ubiquitous use of phthalates in the human environment, but studies have not directly evaluated mortality in relation to these exposures. To evaluate assocns. of phthalate exposure with mortality, and quantify attributable mortality and lost economic productivity in 2013-4 among 55-64 yr olds. This nationally representative cohort study included 5303 adults aged 20 years or older who participated in the US National Health and Nutrition Examn. Survey 2001-2010 and provided urine samples for phthalate metabolite measurements. Participants were linked to mortality data from survey date through Dec. 31, 2015. Data analyses were conducted in July 2020. Mortality from all causes, cardiovascular disease, and cancer. Multivariable models identified increased mortality in relation to high-mol. wt. (HMW) phthalate metabolites, esp. those of di-2-ethylhexylphthalate (DEHP). Hazard ratios (HR) for continuous HMW and DEHP metabolites were 1.14 (95% CI 1.06-1.23) and 1.10 (95% CI 1.03-1.19), resp., with consistently higher mortality in the third tertile (1.48, 95% CI 1.19-1.86; and 1.42, 95% CI 1.13-1.78). Cardiovascular mortality was significantly increased in relation to a prominent DEHP metabolite, mono-(2-ethyl-5-oxohexyl)phthalate. Extrapolating to the population of 55-64 yr old Americans, we identified 90,761-107,283 attributable deaths and $39.9-47.1 billion in lost economic productivity. In a nationally representative sample, phthalate exposures were assocd. with all-cause and cardiovascular mortality, with societal costs approximating $39 billion/yr or more. While further studies are needed to corroborate observations and identify mechanisms, regulatory action is urgently needed.
- 67Davison, M. Pharmaceutical Anti-Counterfeiting: Combating the Real Danger from Fake Drugs; John Wiley & Sons, Inc.: Hoboken, NJ, USA, 2011.There is no corresponding record for this reference.
- 68Ishiyama, R.; Takahashi, T.; Makino, K.; Kudo, Y.; Kooper, M.; Abbink, D., Medicine Tablet Authentication Using “Fingerprints” of Ink-Jet Printed Characters. In 2019 IEEE International Conference on Industrial Technology (ICIT); IEEE, 2019, 871– 876.There is no corresponding record for this reference.
- 69Leem, J. W.; Kim, M. S.; Choi, S. H.; Kim, S. R.; Kim, S. W.; Song, Y. M.; Young, R. J.; Kim, Y. L. Edible unclonable functions. Nat. Commun. 2020, 11, 328, DOI: 10.1038/s41467-019-14066-569https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXivFOgtL8%253D&md5=c0e5a56f89d170f18f3648f07fa38be3Edible unclonable functionsLeem, Jung Woo; Kim, Min Seok; Choi, Seung Ho; Kim, Seong-Ryul; Kim, Seong-Wan; Song, Young Min; Young, Robert J.; Kim, Young L.Nature Communications (2020), 11 (1), 328CODEN: NCAOBW; ISSN:2041-1723. (Nature Research)Abstr.: Counterfeit medicines are a fundamental security problem. Counterfeiting medication poses a tremendous threat to patient safety, public health, and the economy in developed and less developed countries. Current solns. are often vulnerable due to the limited security levels. We propose that the highest protection against counterfeit medicines would be a combination of a phys. unclonable function (PUF) with on-dose authentication. A PUF can provide a digital fingerprint with multiple pairs of input challenges and output responses. On-dose authentication can verify every individual pill without removing the identification tag. Here, we report on-dose PUFs that can be directly attached onto the surface of medicines, be swallowed, and digested. Fluorescent proteins and silk proteins serve as edible photonic biomaterials and the photoluminescent properties provide parametric support of challenge-response pairs. Such edible cryptog. primitives can play an important role in pharmaceutical anti-counterfeiting and other security applications requiring immediate destruction or vanishing features.
- 70Altman, G. H.; Diaz, F.; Jakuba, C.; Calabro, T.; Horan, R. L.; Chen, J. S.; Lu, H.; Richmond, J.; Kaplan, D. L. Silk-based biomaterials. Biomaterials 2003, 24, 401– 416, DOI: 10.1016/S0142-9612(02)00353-870https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BD38nmtlGitg%253D%253D&md5=d66d6bd20f249166630505d09650a120Silk-based biomaterialsAltman Gregory H; Diaz Frank; Jakuba Caroline; Calabro Tara; Horan Rebecca L; Chen Jingsong; Lu Helen; Richmond John; Kaplan David LBiomaterials (2003), 24 (3), 401-16 ISSN:0142-9612.Silk from the silkworm, Bombyx mori, has been used as biomedical suture material for centuries. The unique mechanical properties of these fibers provided important clinical repair options for many applications. During the past 20 years, some biocompatibility problems have been reported for silkworm silk; however, contamination from residual sericin (glue-like proteins) was the likely cause. More recent studies with well-defined silkworm silk fibers and films suggest that the core silk fibroin fibers exhibit comparable biocompatibility in vitro and in vivo with other commonly used biomaterials such as polylactic acid and collagen. Furthermore, the unique mechanical properties of the silk fibers, the diversity of side chain chemistries for 'decoration' with growth and adhesion factors, and the ability to genetically tailor the protein provide additional rationale for the exploration of this family of fibrous proteins for biomaterial applications. For example, in designing scaffolds for tissue engineering these properties are particularly relevant and recent results with bone and ligament formation in vitro support the potential role for this biomaterial in future applications. To date, studies with silks to address biomaterial and matrix scaffold needs have focused on silkworm silk. With the diversity of silk-like fibrous proteins from spiders and insects, a range of native or bioengineered variants can be expected for application to a diverse set of clinical needs.
- 71Cao, Y.; Wang, B. C. Biodegradation of silk biomaterials. Int. J. Mol. Sci. 2009, 10, 1514– 1524, DOI: 10.3390/ijms1004151471https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1MXltFaisLg%253D&md5=8352d1fb9cd5bca578b73612bb06d6d5Biodegradation of silk biomaterialsCao, Yang; Wang, BochuInternational Journal of Molecular Sciences (2009), 10 (4), 1514-1524CODEN: IJMCFK; ISSN:1422-0067. (Molecular Diversity Preservation International)A review. Silk fibroin from the silkworm, Bombyx mori, has excellent properties such as biocompatibility, biodegrdn., non-toxicity, adsorption properties, etc. As a kind of ideal biomaterial, silk fibroin has been widely used since it was first utilized for sutures a long time ago. The degrdn. behavior of silk biomaterials is obviously important for medical applications. This article will focus on silk-based biomaterials and review the degrdn. behaviors of silk materials.
- 72Thurber, A. E.; Omenetto, F. G.; Kaplan, D. L. In vivo bioresponses to silk proteins. Biomaterials 2015, 71, 145– 157, DOI: 10.1016/j.biomaterials.2015.08.03972https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXhtlOgsbjP&md5=0132b88fc83433397da2ced631b6b707In vivo bioresponses to silk proteinsThurber, Amy E.; Omenetto, Fiorenzo G.; Kaplan, David L.Biomaterials (2015), 71 (), 145-157CODEN: BIMADU; ISSN:0142-9612. (Elsevier Ltd.)Silks are appealing materials for numerous biomedical applications involving drug delivery, tissue engineering, or implantable devices, because of their tunable mech. properties and wide range of phys. structures. In addn. to the functionalities needed for specific clin. applications, a key factor necessary for clin. success for any implanted material is appropriate interactions with the body in vivo. This review summarizes our current understanding of the in vivo biol. responses to silks, including degrdn., the immune and inflammatory response, and tissue remodeling with particular attention to vascularization. While we focus in this review on silkworm silk fibroin protein due to the large quantity of in vivo data thanks to its widespread use in medical materials and consumer products, spider silk information is also included if available. Silk proteins are degraded in the body on a time course that is dependent on the method of silk fabrication and can range from hours to years. Silk protein typically induces a mild inflammatory response that decreases within a few weeks of implantation. The response involves recruitment and activation of macrophages and may include activation of a mild foreign body response with the formation of multinuclear giant cells, depending on the material format and location of implantation. The no. of immune cells present decreases with time and granulation tissue, if formed, is replaced by endogenous, not fibrous, tissue. Importantly, silk materials have not been demonstrated to induce mineralization, except when used in calcified tissues. Due to its ability to be degraded, silk can be remodeled in the body allowing for vascularization and tissue ingrowth with eventual complete replacement by native tissue. The degree of remodeling, tissue ingrowth, or other specific cell behaviors can be modulated with addn. of growth or other signaling factors. Silk can also be combined with numerous other materials including proteins, synthetic polymers, and ceramics to enhance its characteristics for a particular function. Overall, the diverse array of silk materials shows excellent bioresponses in vivo with low immunogenicity and the ability to be remodeled and replaced by native tissue making it suitable for numerous clin. applications.
- 73Murphy, A. R.; Kaplan, D. L. Biomedical applications of chemically-modified silk fibroin. J. Mater. Chem. 2009, 19, 6443– 6450, DOI: 10.1039/b905802h73https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1MXhtVOnu7fN&md5=06ce00a9706a565f9f2f57675b45c542Biomedical applications of chemically-modified silk fibroinMurphy, Amanda R.; Kaplan, David L.Journal of Materials Chemistry (2009), 19 (36), 6443-6450CODEN: JMACEP; ISSN:0959-9428. (Royal Society of Chemistry)A review. Silk proteins belong to a class of unique, high mol. wt., block copolymer-like proteins that have found widespread use in biomaterials and regenerative medicine. The useful features of these proteins, including self-assembly, robust mech. properties, biocompatibility and biodegradability can be enhanced through a variety of chem. modifications. These modifications provide chem. handles for the attachment of growth factors, cell binding domains and other polymers to silk, expanding the range of cell and tissue engineering applications attainable. This review focuses on the chem. reactions that have been used to modify the amino acids in silk proteins, and describes their utility in biomedical applications.
- 74Liu, X. F.; Zhang, K. Q. Silk fiber - molecular formation mechanism, structure-property relationship and advanced applications. Oligomerization of Chemical and Biological Compounds 2014, 69– 102, DOI: 10.5772/5761174https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28XlvFGntrg%253D&md5=486e89539bdc76226f5b46e998b8c3a8Silk fiber - molecular formation mechanism, structure-property relationship and advanced applicationsLiu, Xinfang; Zhang, Ke-QinOligomerization of Chemical and Biological Compounds (2014), (), 69-102CODEN: 69UBNH ISSN:. (InTech)A review. This paper focuses on mol. formation mechanism, structure-property relationship and advanced applications of silk fibers. Silk protein assembly, silk fiber formation mechanism and structure and compn. of Bombyx mori and spider dragline silk fibers were also discussed.
- 75Nguyen, T. P.; Nguyen, Q. V.; Nguyen, V. H.; Le, T. H.; Huynh, V. Q. N.; Vo, D. V. N.; Trinh, Q. T.; Kim, S. Y.; Le, Q. V. Silk Fibroin-Based Biomaterials for Biomedical Applications: A Review. Polymers 2019, 11, 1933, DOI: 10.3390/polym1112193375https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1MXisVSiur7F&md5=3a30f84273eac5dfaf2599da4253eb15Silk fibroin-based biomaterials for biomedical applications: a reviewNguyen, Thang Phan; Nguyen, Quang Vinh; Nguyen, Van-Huy; Le, Thu-Ha; Huynh, Vu Quynh Nga; Vo, Dai-Viet N.; Trinh, Quang Thang; Kim, Soo Young; Van Le, QuyetPolymers (Basel, Switzerland) (2019), 11 (12), 1933CODEN: POLYCK; ISSN:2073-4360. (MDPI AG)A review. Since it was first discovered, thousands of years ago, silkworm silk has been known to be an abundant biopolymer with a vast range of attractive properties. The utilization of silk fibroin (SF), the main protein of silkworm silk, has not been limited to the textile industry but has been further extended to various high-tech application areas, including biomaterials for drug delivery systems and tissue engineering. The outstanding mech. properties of SF, including its facile processability, superior biocompatibility, controllable biodegrdn., and versatile functionalization have allowed its use for innovative applications. In this review, we describe the structure, compn., general properties, and structure-properties relationship of SF. In addn., the methods used for the fabrication and modification of various materials are briefly addressed. Lastly, recent applications of SF-based materials for small mol. drug delivery, biol. drug delivery, gene therapy, wound healing, and bone regeneration are reviewed and our perspectives on future development of these favorable materials are also shared.
- 76Jaramillo-Quiceno, N.; Restrepo-Osorio, A. Water-annealing treatment for edible silk fibroin coatings from fibrous waste. J. Appl. Polym. Sci. 2020, 137, 48505, DOI: 10.1002/app.4850576https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1MXhslOhurnP&md5=5cbf50df740941ac1399fdd4075301b5Water-annealing treatment for edible silk fibroin coatings from fibrous wasteJaramillo-Quiceno, N.; Restrepo-Osorio, A.Journal of Applied Polymer Science (2020), 137 (13), 48505CODEN: JAPNAB; ISSN:0021-8995. (John Wiley & Sons, Inc.)Silk fibroin (SF) is an engineered biopolymer with properties that are desirable for the development of food preservation materials, such as edible coatings or packaging. In this study, SF from fibrous waste was assessed for the first time as an edible coating for strawberries. Relationships were established between the structural properties of SF thin films obtained from silk waste, both untreated (SFW) and water annealed (WA-SFW) and their morphol. and performance as edible strawberry coatings. According to the results obtained, the water-annealing treatment led to a structural modification in SF films. The strawberries coated with WA-SFW exhibited better performance during storage by reducing wt. loss and preserving its visual appearance. The anal. of metal contaminants showed that SFs obtained from fibrous waste are relatively nontoxic. Therefore, using this raw material for the development of edible coatings in perishable fruits is considered promising. © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2019, 136, 48505.
- 77Sun, H.; Marelli, B. Growing silk fibroin in advanced materials for food security. MRS Commun. 2021, 11, 31– 45, DOI: 10.1557/s43579-020-00003-x77https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB38XjvFWrt78%253D&md5=76713e29d579ca656c7b0b6be8c5d01bGrowing silk fibroin in advanced materials for food securitySun, Hui; Marelli, BenedettoMRS Communications (2021), 11 (1), 31-45CODEN: MCROF8; ISSN:2159-6867. (Springer International Publishing AG)Abstr.: This perspective provides an overview of the micro-/nanofabrication methods developed for structural biopolymers, highlighting recent advances in the rapid and ease construction of complex and multifunctional silk fibroin-based devices by integrating top-down manufg. with bottom-up mol. self-assembly. Of particular interest is the development of a new nanofabrication strategy that employs templated crystn. to direct silk fibroin folding and assembly from a suspension of disordered, random coil mols. to ordered, hierarchical mesostructured materials. Such advancements in structural biopolymers fabrication provide the basis for engineering a new generation of tech. materials that can be interfaced with food and plants.
- 78Ruggeri, E.; Kim, D. Y.; Cao, Y. T.; Fare, S.; De Nardo, L.; Marelli, B. A multilayered edible coating to extend produce shelf life. ACS Sustain. Chem. Eng. 2020, 8, 14312– 14321, DOI: 10.1021/acssuschemeng.0c03365There is no corresponding record for this reference.
- 79Tao, H.; Brenckle, M. A.; Yang, M. M.; Zhang, J. D.; Liu, M. K.; Siebert, S. M.; Averitt, R. D.; Mannoor, M. S.; McAlpine, M. C.; Rogers, J. A.; Kaplan, D. L.; Omenetto, F. G. Silk-based conformal, adhesive, edible food sensors. Adv. Mater. 2012, 24, 1067– 1072, DOI: 10.1002/adma.20110381479https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC38XhtFSnsLk%253D&md5=689c0895d06c048f2f6a798782897c93Silk-Based Conformal, Adhesive, Edible Food SensorsTao, Hu; Brenckle, Mark A.; Yang, Miaomiao; Zhang, Jingdi; Liu, Mengkun; Siebert, Sean M.; Averitt, Richard D.; Mannoor, Manu S.; McAlpine, Michael C.; Rogers, John A.; Kaplan, David L.; Omenetto, Fiorenzo G.Advanced Materials (Weinheim, Germany) (2012), 24 (8), 1067-1072CODEN: ADVMEW; ISSN:0935-9648. (Wiley-VCH Verlag GmbH & Co. KGaA)In this paper, the authors present a concept for making wireless passive antennas on silk substrates across multiple regions of the electromagnetic spectrum. These antennas can be easily applied to curved objects and adhere conformally. The devices were tested for function by monitoring their resonant responses continuously during spoilage process to assess the potential monitor changes in food quality. Proof-of-principle demonstrations for this type of approach are demonstrated by monitoring fruit ripening with a confromally attached RFID-like silk sensor transferred onto the fruit skin, and spoilage of dairy products through surface contact (in the solid fcase) or immersion (for liq. goods). These types of passive, chip-less sensor, consists of an antenna or an array of antennas/resonators made of only a sub-micron thickness of gold, a level equiv. to common edible gold leaf/flakes used on cakes and chocolates. The resonators are fabricated on pure-protein silk film substrates, and can be used as sensing platforms that safely interface with consumable goods or can be in direct contact with food (and can potentially be consumed) for different applications.
- 80Marelli, B.; Brenckle, M. A.; Kaplan, D. L.; Omenetto, F. G. Silk fibroin as edible coating for perishable food preservation. Sci. Rep. 2016, 6, 25263, DOI: 10.1038/srep2526380https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28XnsV2jtbg%253D&md5=dc0c0924e7ec68ec9f4e4adaf3c9114bSilk Fibroin as Edible Coating for Perishable Food PreservationMarelli, B.; Brenckle, M. A.; Kaplan, D. L.; Omenetto, F. G.Scientific Reports (2016), 6 (), 25263CODEN: SRCEC3; ISSN:2045-2322. (Nature Publishing Group)The regeneration of structural biopolymers into micelles or nanoparticles suspended in water has enabled the design of new materials with unique and compelling properties that can serve at the interface between the biotic and the abiotic worlds. In this study, we leveraged silk fibroin quintessential properties (i.e. polymorphism, conformability and hydrophobicity) to design a water-based protein suspension that self-assembles on the surface of food upon dip coating. The water-based post-processing control of the protein polymorphism enables the modulation of the diffusion of gases through the silk fibroin thin membranes (e.g. O2 and CO2 diffusion, water vapor permeability), which is a key parameter to manage food freshness. In particular, an increased beta-sheet content corresponds to a redn. in oxygen diffusion through silk fibroin thin films. By using the dip coating of strawberries and bananas as proof of principle, we have shown that the formation of micrometre-thin silk fibroin membranes around the fruits helps the management of postharvest physiol. of the fruits. Thus, silk fibroin coatings enhance fruits' shelf life at room conditions by reducing cell respiration rate and water evapn. The water-based processing and edible nature of silk fibroin makes this approach a promising alternative for food preservation with a naturally derived material.
- 81Leem, J. W.; Fraser, M. J.; Kim, Y. L. Transgenic and diet-enhanced silk production for reinforced biomaterials: A metamaterial perspective. Annu. Rev. Biomed. Eng. 2020, 22, 79– 102, DOI: 10.1146/annurev-bioeng-082719-03274781https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXks1Ojur0%253D&md5=a1d65d0f021ea0d24bd1e1952a19de42Transgenic and Diet-Enhanced Silk Production for Reinforced Biomaterials: A Metamaterial PerspectiveLeem, Jung Woo; Fraser, Malcolm J.; Kim, Young L.Annual Review of Biomedical Engineering (2020), 22 (), 79-102CODEN: ARBEF7; ISSN:1523-9829. (Annual Reviews)Silk fibers, which are protein-based biopolymers produced by spiders and silkworms, are fascinating biomaterials that have been extensively studied for numerous biomedical applications. Silk fibers often have remarkable phys. and biol. properties that typical synthetic materials do not exhibit. These attributes have prompted a wide variety of silk research, including genetic engineering, biotechnol. synthesis, and bioinspired fiber spinning, to produce silk proteins on a large scale and to further enhance their properties. In this review, we describe the basic properties of spider silk and silkworm silk and the important prodn. methods for silk proteins. We discuss recent advances in reinforced silk using silkworm transgenesis and functional additive diets with a focus on biomedical applications. We also explain that reinforced silk has an analogy with metamaterials such that user-designed atypical responses can be engineered beyond what naturally occurring materials offer. These insights into reinforced silk can guide better engineering of superior synthetic biomaterials and lead to discoveries of unexplored biol. and medical applications of silk.
- 82Elick, T. A.; Bauser, C. A.; Fraser, M. J. Excision of the piggyBac transposable element in vitro is a precise event that is enhanced by the expression of its encoded transposase. Genetica 1996, 98, 33– 41, DOI: 10.1007/BF0012021682https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaK28Xlslyntb8%253D&md5=023e75b34c00b99bbc55d7df713c76b0Excision of the piggyBac transposable element in vitro is a precise event that is enhanced by the expression of its encoded transposaseElick, Teresa A.; Bauser, Christopher A.; Fraser, M. J.Genetica (The Hague) (1996), 98 (1), 33-41CODEN: GENEA3; ISSN:0016-6707. (Kluwer)The piggyBac Lepidopteran transposable element moves from the cellular genome into infecting baculovirus genomes during passage of the virus in cultured TN-368 cells. We have constructed genetically tagged piggyBac elements that permit anal. of excision when transiently introduced on plasmids into the piggyBac-deficient Spodoptera frugiperda IPLB-SF21AE cell line. Precise excision of the element from these plasmids occurs at a higher frequency in the presence of a helper plasmid that presumably supplies the piggyBac transposase. The results suggest that the piggyBac transposon encodes a protein that functions to facilitate not only insertion, but precise excision as well. This is the first demonstration of piggyBac mobility from plasmid sources in uninfected Lepidopteran cells.
- 83Tamura, T.; Thibert, C.; Royer, C.; Kanda, T.; Eappen, A.; Kamba, M.; Komoto, N.; Thomas, J.-L.; Mauchamp, B.; Chavancy, G.; Shirk, P.; Fraser, M.; Prudhomme, J.-C.; Couble, P. Germline transformation of the silkworm Bombyx mori L. using a piggyBac transposon-derived vector. Nat. Biotechnol. 2000, 18, 81– 84, DOI: 10.1038/7197883https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BD3c%252FptFWnug%253D%253D&md5=9664d1a425972c400ba7f7a9e9b51fd0Germline transformation of the silkworm Bombyx mori L. using a piggyBac transposon-derived vectorTamura T; Thibert C; Royer C; Kanda T; Abraham E; Kamba M; Komoto N; Thomas J L; Mauchamp B; Chavancy G; Shirk P; Fraser M; Prudhomme J C; Couble P; Toshiki T; Chantal T; Corinne R; Toshio K; Eappen A; Mari K; Natuo K; Jean-Luc T; Bernard M; Gerard C; Paul S; Malcolm F; Jean-Claude P; Pierre CNature biotechnology (2000), 18 (1), 81-4 ISSN:1087-0156.We have developed a system for stable germline transformation in the silkworm Bombyx mori L. using piggyBac, a transposon discovered in the lepidopteran Trichoplusia ni. The transformation constructs consist of the piggyBac inverted terminal repeats flanking a fusion of the B. mori cytoplasmic actin gene BmA3 promoter and the green fluorescent protein (GFP). A nonautonomous helper plasmid encodes the piggyBac transposase. The reporter gene construct was coinjected into preblastoderm eggs of two strains of B. mori. Approximately 2% of the individuals in the G1 broods expressed GFP. DNA analyses of GFP-positive G1 silkworms revealed that multiple independent insertions occurred frequently. The transgene was stably transferred to the next generation through normal Mendelian inheritance. The presence of the inverted terminal repeats of piggyBac and the characteristic TTAA sequence at the borders of all the analyzed inserts confirmed that transformation resulted from precise transposition events. This efficient method of stable gene transfer in a lepidopteran insect opens the way for promising basic research and biotechnological applications.
- 84Li, X. H.; Burnight, E. R.; Cooney, A. L.; Malani, N.; Brady, T.; Sander, J. D.; Staber, J.; Wheelan, S. J.; Joung, J. K.; McCray, P. B.; Bushman, F. D.; Sinn, P. L.; Craig, N. L. piggyBac transposase tools for genome engineering. Proc. Natl. Acad. Sci. 2013, 110, E2279– E2287, DOI: 10.1073/pnas.130598711084https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXhtFOmsLjK&md5=f337d469cb39a1bbb07a572d1d10ac62piggyBac transposase tools for genome engineeringLi, Xianghong; Burnight, Erin R.; Cooney, Ashley L.; Malani, Nirav; Brady, Troy; Sander, Jeffry D.; Staber, Janice; Wheelan, Sarah J.; Joung, J. Keith; McCray, Paul B., Jr.; Bushman, Frederic D.; Sinn, Patrick L.; Craig, Nancy L.Proceedings of the National Academy of Sciences of the United States of America (2013), 110 (25), E2279-E2287, SE2279/1-SE2279/8CODEN: PNASA6; ISSN:0027-8424. (National Academy of Sciences)The transposon piggyBac is being used increasingly for genetic studies. Here, the authors describe modified versions of piggyBac transposase that have potentially wide-ranging applications, such as reversible transgenesis and modified targeting of insertions. PiggyBac is distinguished by its ability to excise precisely, restoring the donor site to its pretransposon state. This characteristic makes piggyBac useful for reversible transgenesis, a potentially valuable feature when generating induced pluripotent stem cells without permanent alterations to genomic sequence. To avoid further genome modification following piggyBac excision by reintegration, the authors generated an excision competent/integration defective (Exc+Int-) transposase. Their findings also suggest the position of a target DNA-transposase interaction. Another goal of genome engineering is to develop reagents that can guide transgenes to preferred genomic regions. Others have shown that piggyBac transposase can be active when fused to a heterologous DNA-binding domain. An Exc+Int- transposase, the intrinsic targeting of which is defective, might also be a useful intermediate in generating a transposase whose integration activity could be rescued and redirected by fusion to a site-specific DNA-binding domain. Fusion to two designed zinc finger proteins rescued the Int- phenotype. Successful guided transgene integration into genomic DNA would have broad applications to gene therapy and mol. genetics. Thus, an Exc+Int- transposase is a potentially useful reagent for genome engineering and provides insight into the mechanism of transposase-target DNA interaction.
- 85Leem, J. W.; Allcca, A. E. L.; Kim, Y. J.; Park, J.; Kim, S. W.; Kim, S. R.; Ryu, W. H.; Chen, Y. P.; Kim, Y. L. Photoelectric silk via genetic encoding and bioassisted plasmonics. Adv. Biosyst. 2020, 4, 2000040, DOI: 10.1002/adbi.20200004085https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXhtl2gsrnN&md5=175389a77b1cd508998f69ac44e6c3cfPhotoelectric Silk via Genetic Encoding and Bioassisted PlasmonicsLeem, Jung Woo; Llacsahuanga Allcca, Andres E.; Kim, Yong Jae; Park, Jongwoo; Kim, Seong-Wan; Kim, Seong-Ryul; Ryu, WonHyoung; Chen, Yong P.; Kim, Young L.Advanced Biosystems (2020), 4 (7), 2000040CODEN: ABDIHL; ISSN:2366-7478. (Wiley-VCH Verlag GmbH & Co. KGaA)Genetically encoded photoelec. silk that can convert photons to electrons (light to electricity) over a wide visible range in a self-power mode is reported. As silk is a versatile host material with elec. cond., biocompatibility, and processability, a photoelec. protein is genetically fused with silk by silkworm transgenesis. Specifically, mKate2, which is conventionally known as a far-red fluorescent protein, is used as a photoelec. protein. Characterization of the electrochem. and optical properties of mKate2 silk allows designing a photoelec. measurement system. A series of in situ photocurrent expts. support the sensitive and stable performance of photoelec. conversion. In addn., as a plasmonic nanomaterial with a broad spectral resonance, titanium nitride (TiN) nanoparticles are biol. hybridized into the silk glands, taking full advantage of the silkworms' open circulatory system as well as the absorption band of mKate2 silk. This biol. hybridization via direct feeding of TiN nanoparticles further enhances the overall photoelec. conversion ability of mKate2 silk. It is envisioned that the biol. derived photoelec. protein, its ecofriendly scalable prodn. by transgenic silkworms, and the bioassisted plasmonic hybridization can potentially broaden the biomaterial choices for developing next-generation biosensing, retina prosthesis, and neurostimulation applications.
- 86Leem, J. W.; Choi, S. H.; Kim, S. R.; Kim, S. W.; Choi, K. H.; Kim, Y. L. Scalable and continuous nanomaterial integration with transgenic fibers for enhanced photoluminescence. Mater. Horiz. 2017, 4, 281– 289, DOI: 10.1039/C6MH00423G86https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXht1amtrg%253D&md5=957eb6d3f70529aabe9dca24b69141dfScalable and continuous nanomaterial integration with transgenic fibers for enhanced photoluminescenceLeem, Jung Woo; Choi, Seung Ho; Kim, Seong-Ryul; Kim, Seong-Wan; Choi, Kwang-Ho; Kim, Young L.Materials Horizons (2017), 4 (2), 281-289CODEN: MHAOBM; ISSN:2051-6355. (Royal Society of Chemistry)For widespread practical translation and utilization of plasmonics and nanophotonics, there is always a need for scalable, cost-effective, eco-friendly, and nontoxic prodn. of nanomaterials and nanostructures. As alternative fabrication and synthesis approaches, insects have received considerable attention as bioreactors and biosynthesis factories. However, scalable fabrication of plasmonic nanomaterials and their integration into flexible and wearable components are still limited. We show that a unique combination of a silkworm factory and green chem. appears to be an effective hybridizing platform for integrating natural biomaterials and metal nanoparticles. Our approach is inspired by a two-century-old method of increasing the wt. of silk fabrics for high price (also known as silk weighting). The reported plasmonics hybridization of silk results in the formation of silver nanoparticles in the interfibrillar space of silk fibers, which is manifested by the 'lustrous' or 'silvery' color of silk. We further demonstrate the plasmon-enhanced photoluminescence of far-red fluorescent protein in silk produced by genetically engineered silkworms (i.e., silkworm transgenesis). Our results provide the groundwork for exploiting native silk as a photonic hybridization platform to implement embedded functionalities in a fiber geometry, which could easily be woven or constructed into large-area and continuous fabrics using existing textile infrastructures in a sustainable manner.
- 87Tschorn, N.; Berg, K.; Stitz, J. Transposon vector-mediated stable gene transfer for the accelerated establishment of recombinant mammalian cell pools allowing for high-yield production of biologics. Biotechnol. Lett. 2020, 42, 1103– 1112, DOI: 10.1007/s10529-020-02889-y87https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXotVChsrs%253D&md5=afc64d72788bd460298d9820fe493633Transposon vector-mediated stable gene transfer for the accelerated establishment of recombinant mammalian cell pools allowing for high-yield production of biologicsTschorn, Natalie; Berg, Karen; Stitz, JoernBiotechnology Letters (2020), 42 (7), 1103-1112CODEN: BILED3; ISSN:0141-5492. (Springer)A review. Stable recombinant mammalian cells are of growing importance in pharmaceutical biotechnol. prodn. scenarios for biologics such as monoclonal antibodies, growth and blood factors, cytokines and subunit vaccines. However, the establishment of recombinant producer cells using classical stable transfection of plasmid DNA is hampered by low stable gene transfer efficiencies. Consequently, subsequent selection of transgenic cells and the screening of clonal cell populations are time- and thus cost-intensive. To overcome these limitations, expression cassettes were embedded into transposon-derived donor vectors. Upon the co-transfection with transposase-encoding constructs, elevated vector copy nos. stably integrated into the genomes of the host cells are readily achieved facilitating under stringent selection pressure the establishment of cell pools characterized by sustained and high-yield recombinant protein prodn. Here, we discuss some aspects of transposon vector technologies, which render these vectors promising candidates for their further utilization in the prodn. of biologics.
- 88Jang, K. M.; Kim, S. G.; Park, J. Y.; Choi, W. H.; Lee, J. W.; Jegal, H. Y.; Kweon, S. J.; Choi, K. H.; Park, J. H. Single-dose oral toxicity study of genetically modified silkworm expressing EGFP protein in icr mouse. Korean J. Agric. Sci. 2016, 43, 109– 115, DOI: 10.7744/kjoas.2016001388https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXhsVGgtb7K&md5=f6cf4b007b6e94f752067bf7d11d16e6Single-dose oral toxicity study of genetically modified silkworm expressing EGFP protein in ICR mouseJang, Kyung-min; Kim, Sung-Gun; Park, Ji-Young; Choi, Won-Ho; Lee, Jae-Woo; Jegal, Hyeon-Young; Kweon, Soon-jong; Choi, Kwang-ho; Park, Jung-hoKorean Journal of Agricultural Science (2016), 43 (1), 109-115CODEN: KJASAP; ISSN:2466-2410. (CNU Institute of Agricultural Science)Silk has had a reputation as a luxurious and sensuous fabric but it is not popular due to the expensive price and poor durability. To develop the silk materials that apply the various industries, the artificially synthesized gene can be introduced into the silkworm and expressed in the silk gland. Transgenic silkworms for the mass prodn. of green fluorescent silks are generated using a fibroin H-chain expression system. For com. use, safety assessment of the transgenic silkworms is essential. The purpose of this study was to examine the potential acute oral toxicity of EGFP protein expressed in genetically modified (GM) fluorescence silkworm and to obtain the approximative LD in the male and female at 6-wk ICR mice. EGFP protein was fed at a dose of 2,000 mg/kg body wt. in five male or five female mice. Mortalities, clin. findings and body wt. changes were monitored for 1, 3, 7, 14 days after dosing. At the end of 14 day observation period, all mice were sacrificed, and the postmortem necropsy were performed. The test group was not obsd. death case. Also the effect was not admitted by test substance administration in common symptoms, the body wt. and postmortem. The results of single-dose oral toxicity test showed that approximative LD of EGFP protein expressed in fluorescence silkworm was considered to exceed the 2,000 mg/kg body wt. in both sexes.
- 89Richards, H. A.; Han, C. T.; Hopkins, R. G.; Failla, M. L.; Ward, W. W.; Stewart, C. N. Safety assessment of recombinant green fluorescent protein orally administered to weaned rats. J. Nutr. 2003, 133, 1909– 1912, DOI: 10.1093/jn/133.6.190989https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD3sXks1Grsr8%253D&md5=91977091dcc87c928350fa5a6ed3bbf7Safety assessment of recombinant green fluorescent protein orally administered to weaned ratsRichards, Harold A.; Han, Chung-Ting; Hopkins, Robin G.; Failla, Mark L.; Ward, William W.; Stewart, C. Neal, Jr.Journal of Nutrition (2003), 133 (6), 1909-1912CODEN: JONUAI; ISSN:0022-3166. (American Society for Nutritional Sciences)Several proposed biotechnol. applications of green fluorescent protein (GFP) are likely to result in its introduction into the food supply of domestic animals and man. We fed pure GFP and diets contg. transgenic canola expressing GFP to young 4-wk-old male Long-Evans Hooded rats for 26 days to evaluate the potential toxicity and allergenicity of GFP. Animals (n = 8/group) were fed AIN-93G diet (control), control diet plus 1.0 mg purified GFP daily, modified control diet with 200 g canola (Brassica rapa cultivar Westar)/kg feed, or control diet with 200 g transgenic canola with 2 levels of GFP/kg feed. Ingestion of GFP did not affect growth, food intake, relative wt. of intestine or other organs, or activities of hepatic enzymes in blood serum. Comparison of the amino acid sequence of GFP to known food allergens revealed that the greatest no. of consecutive amino acid matches between GFP and any food allergen was 4, suggesting the absence of common allergen epitopes. GFP was rapidly degraded during simulated gastric digestion. The data indicate that GFP is a low allergenicity risk and provide preliminary indications that GFP is not likely to pose a health risk.
- 90Kim, D. W.; Lee, O. J.; Kim, S. W.; Ki, C. S.; Chao, J. R.; Yoo, H.; Yoon, S. I.; Lee, J. E.; Park, Y. R.; Kweon, H.; Lee, K. G.; Kaplan, D. L.; Park, C. H. Novel fabrication of fluorescent silk utilized in biotechnological and medical applications. Biomaterials 2015, 70, 48– 56, DOI: 10.1016/j.biomaterials.2015.08.02590https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXhtlCksbfI&md5=49dbf2b254e576ae3db706cf9bc97f31Novel fabrication of fluorescent silk utilized in biotechnological and medical applicationsKim, Dong Wook; Lee, Ok Joo; Kim, Seong-Wan; Ki, Chang Seok; Chao, Janet Ren; Yoo, Hyojong; Yoon, Sung-il; Lee, Jeong Eun; Park, Ye Ri; Kweon, HaeYong; Lee, Kwang Gill; Kaplan, David L.; Park, Chan HumBiomaterials (2015), 70 (), 48-56CODEN: BIMADU; ISSN:0142-9612. (Elsevier Ltd.)Silk fibroin (SF) is a natural polymer widely used and studied for diverse applications in the biomedical field. Recently, genetically modified silks, particularly fluorescent SF fibers, were reported to have been produced from transgenic silkworms. However, they are currently limited to textile manufg. To expand the use of transgenic silkworms for biomedical applications, a soln. form of fluorescent SF needed to be developed. Here, we describe a novel method of prepg. a fluorescent SF soln. and demonstrate long-term fluorescent function up to one year after s.c. insertion. We also show that fluorescent SF labeled p53 antibodies clearly identify HeLa cells, indicating the applicability of fluorescent SF to cancer detection and bio-imaging. Furthermore, we demonstrate the intraoperative use of fluorescent SF in an animal model to detect a small esophageal perforation (0.5 mm). This study suggests how fluorescent SF biomaterials can be applied in biotechnol. and clin. medicine.
- 91Leem, J. W.; Park, J.; Kim, S. W.; Kim, S. R.; Choi, S. H.; Choi, K. H.; Kim, Y. L. Green light-activated photoreaction via genetic hybridization of far-red fluorescent protein and silk. Adv. Sci. 2018, 5, 1700863, DOI: 10.1002/advs.20170086391https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BB3c%252FhtlOhug%253D%253D&md5=fcb1607d1d6f6bcc00ff45eed9679c8eGreen-Light-Activated Photoreaction via Genetic Hybridization of Far-Red Fluorescent Protein and SilkLeem Jung Woo; Choi Seung Ho; Kim Young L; Park Jongwoo; Kim Seong-Wan; Kim Seong-Ryul; Choi Kwang-Ho; Kim Young L; Kim Young LAdvanced science (Weinheim, Baden-Wurttemberg, Germany) (2018), 5 (6), 1700863 ISSN:2198-3844.Fluorescent proteins often result in phototoxicity and cytotoxicity, in particular because some red fluorescent proteins produce and release reactive oxygen species (ROS). The photogeneration of ROS is considered as a detrimental side effect in cellular imaging or is proactively utilized for ablating cancerous tissue. As ancient textiles or biomaterials, silk produced by silkworms can directly be used as fabrics or be processed into materials and structures to host other functional nanomaterials. It is reported that transgenic fusion of far-red fluorescent protein (mKate2) with silk provides a photosensitizer hybridization platform for photoinducible control of ROS. Taking advantage of green (visible) light activation, native and regenerated mKate2 silk can produce and release superoxide and singlet oxygen, in a comparable manner of visible light-driven plasmonic photocatalysis. Thus, the genetic expression of mKate2 in silk offers immediately exploitable and scalable photocatalyst-like biomaterials. It is further envisioned that mKate2 silk can potentially rule out hazardous concerns associated with foreign semiconductor photocatalytic nanomaterials.
- 92Marcinkevicius, P.; Bagci, I. B.; Abdelazim, N. M.; Woodhead, C. S.; Young, R. J.; Roedig, U. Optically Interrogated Unique Object with Simulation Attack Prevention; Design, Automation & Test in Europe Conference & Exhibition (DATE), Florence, Italy, 2019.There is no corresponding record for this reference.
- 93Park, J.; Leem, J. W.; Ku, Z. Y.; Kim, J. O.; Chegal, W. C.; Kang, S. W.; Kim, Y. L. Disordered heteronanostructures of MoS2 and TiO2 for unclonable cryptographic primitives. ACS Appl. Nano Mater. 2021, 4, 2076– 2085, DOI: 10.1021/acsanm.0c0336793https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3MXislGjsLc%253D&md5=6a1efeed69384de3db6862e715b7ccc0Disordered Heteronanostructures of MoS2 and TiO2 for Unclonable Cryptographic PrimitivesPark, Jaeseo; Leem, Jung Woo; Ku, Zahyun; Kim, Jun Oh; Chegal, Won C.; Kang, Sang-Woo; Kim, Young L.ACS Applied Nano Materials (2021), 4 (2), 2076-2085CODEN: AANMF6; ISSN:2574-0970. (American Chemical Society)In the era of hyperconnected contemporary society, hardware and information security become more dependent on advanced cryptog. primitives. A phys. unclonable function (PUF), originally implemented by an algorithmic means as software-based security, is considered as an immediate security soln. Nanomaterial-based PUFs have recently received considerable attention but have often limitations on unclonability and scalability for practical applications. Here, we report that heteronanostructures of vertically orientated molybdenum disulfide (MoS2) nanoflakes and titanium dioxide (TiO2) aggregates can be used for a versatile PUF. The band alignment of heteronanostructured MoS2/TiO2 results in photogenerated electron transfer and turns off the bright state of emitters, offering an entropy source. After von Neumann debiasing, extd. cryptog. keys show a large encoding capacity and reliable PUF performance, including randomness, uniqueness, reproducibility, low false rates, and long-term stability. The unique hybridization of the most common semiconductor nanomaterials could not only offer inherent asymmetry not to be cloned for a PUF but also guarantee scalable nanomanufg. strategies to augment cryptosystems.
- 94Leem, J. W.; Choi, M.; Yu, J. S. Multifunctional microstructured polymer films for boosting solar power generation of silicon-based photovoltaic modules. ACS Appl. Mater. Interfaces 2015, 7, 2349– 2358, DOI: 10.1021/am506819494https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXhsF2jtLY%253D&md5=9fe9e7c90a7c8672673087f5b9542460Multifunctional Microstructured Polymer Films for Boosting Solar Power Generation of Silicon-Based Photovoltaic ModulesLeem, Jung Woo; Choi, Minkyu; Yu, Jae SuACS Applied Materials & Interfaces (2015), 7 (4), 2349-2358CODEN: AAMICK; ISSN:1944-8244. (American Chemical Society)The authors propose 2-dimensional periodic conical micrograting structured (MGS) polymer films as a multifunctional layer (i.e., light harvesting and self-cleaning) at the surface of outer polyethylene terephthalate (PET) cover-substrates for boosting the solar power generation in Si-based photovoltaic (PV) modules. The surface of UV-curable NOA63 MGS polymer films fabricated by the soft imprint lithog. exhibits a hydrophobic property with H2O contact angle of ∼121° at no inclination and dynamic advancing/receding H2O contact angles of ∼132°/111° at the inclination angle of 40°, resp., which can remove dust particles or contaminants on the surface of PV modules in real outdoor environments (i.e., self-cleaning). The NOA63 MGS film coated on the bare PET leads to the redn. of reflection as well as the enhancement of both the total and diffuse transmissions at wavelengths of 300-1100 nm, indicating lower solar weighted reflectance (RSW) of ∼8.2%, higher solar weighted transmittance (TSW) of ∼93.1%, and considerably improved av. haze ratio (HAvg) of ∼88.3% as compared to the bare PET (i.e., RSW ≈ 13.5%, TSW ≈ 86.9%, and HAvg ≈ 9.1%), resp. Addnl., it shows a relatively good durability at temps. of ≤160°. The resulting Si PV module with the NOA63 MGS/PET has an enhanced power conversion efficiency (PCE) of 13.26% (cf., PCE = 12.55% for the ref. PV module with the bare PET) due to the mainly improved short circuit current from 49.35 to 52.01 mA, exhibiting the PCE increment percentage of ∼5.7%. For light incident angle-dependent PV module current-voltage characteristics, superior solar energy conversion properties are also obtained in a broad angle range of 10-80°.
- 95Leem, J. W.; Lee, S. H.; Guan, X. Y.; Yu, J. S. Inverted tetrahedron-pyramidal micropatterned polymer films for boosting light output power in flip-chip light-emitting diodes. Opt. Express 2015, 23, 9612– 9617, DOI: 10.1364/OE.23.00961295https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXksFWhsrw%253D&md5=ab4628638e6ee8867eb6db25f6c0466eInverted tetrahedron-pyramidal micropatterned polymer films for boosting light output power in flip-chip light-emitting diodesLeem, Jung Woo; Lee, Soo Hyun; Guan, Xiang-Yu; Yu, Jae SuOptics Express (2015), 23 (8), 9612-9617CODEN: OPEXFF; ISSN:1094-4087. (Optical Society of America)We report the improved light output power in gallium nitridebased green flip-chip light-emitting diodes (FCLEDs) employed with inverted tetrahedron-pyramidal micropatterned polydimethylsiloxane (ITPM PDMS) films as an encapsulation and protection layer. The micropatterns are transferred into the surface of PDMS films from the sapphire substrate master molds with two-dimensional periodic hexagonal TPM arrays by a soft imprint lithog. method. The ITPM PDMS film laminated on the sapphire dramatically enhances the diffuse transmittance (TD) in a wavelength (λ) range of 400-650 nm, exhibiting the larger TD value of ∼53% at λ = 525 nm, (cf., TD ∼1% for planar sapphire). By introducing the ITPM PDMS film on the outer surface of sapphire in FCLEDs, the light output power is enhanced, indicating the increment percentage of ∼11.1% at 500 mA of injection current compared to the ref. FCLED without the ITPM PDMS film, together with better electroluminescence intensity and far-field radiation pattern.
- 96Nogueira, G. M.; Rodas, A. C. D.; Leite, C. A. P.; Giles, C.; Higa, O. Z.; Polakiewicz, B.; Beppu, M. M. Preparation and characterization of ethanol-treated silk fibroin dense membranes for biomaterials application using waste silk fibers as raw material. Bioresour. Technol. 2010, 101, 8446– 8451, DOI: 10.1016/j.biortech.2010.06.06496https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3cXoslyns70%253D&md5=b1f0e89090b5ee1730c46f7f2bd67989Preparation and characterization of ethanol-treated silk fibroin dense membranes for biomaterials application using waste silk fibers as raw materialNogueira, Grinia M.; Rodas, Andrea C. D.; Leite, Carlos A. P.; Giles, Carlos; Higa, Olga Z.; Polakiewicz, Bronislaw; Beppu, Marisa M.Bioresource Technology (2010), 101 (21), 8446-8451CODEN: BIRTEB; ISSN:0960-8524. (Elsevier Ltd.)The possibility of producing valued devices from low cost natural resources is a subject of broad interest. The present study explores the prepn. and characterization of silk fibroin dense membranes using waste silk fibers from textile processing. Morphol., crystallinity, thermal resistance and cytotoxicity of membranes as well as the changes on the secondary structure of silk fibroin were analyzed after undergoing treatment with ethanol. Membranes presented amorphous patterns as detd. via X-ray diffraction. The secondary structure of silk fibroin on dense membranes was either random coil (silk I) or β-sheet (silk II), before and after ethanol treatment, resp. The sterilized membranes presented no cytotoxicity to endothelial cells during in vitro assays. This fact stresses the material potential to be used in the fabrication of biomaterials, as coatings of cardiovascular devices and as membranes for wound dressing or drug delivery systems.
- 97Qi, Y.; Wang, H.; Wei, K.; Yang, Y.; Zheng, R. Y.; Kim, I. S.; Zhang, K. Q. A review of structure construction of silk fibroin biomaterials from single structures to multi-level structures. Int. J. Mol. Sci. 2017, 18, 237, DOI: 10.3390/ijms1803023797https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1cXkvVShsrg%253D&md5=9837f43dc3bd91ae5f81e72a30508acaA review of structure construction of silk fibroin biomaterials from single structures to multi-level structuresQi, Yu; Wang, Hui; Wei, Kai; Yang, Ya; Zheng, Ru-Yue; Kim, Ick Soo; Zhang, Ke-QinInternational Journal of Molecular Sciences (2017), 18 (3), 237/1-237/21CODEN: IJMCFK; ISSN:1422-0067. (MDPI AG)The biol. performance of artificial biomaterials is closely related to their structure characteristics. Cell adhesion, migration, proliferation, and differentiation are all strongly affected by the different scale structures of biomaterials. Silk fibroin (SF), extd. mainly from silkworms, has become a popular biomaterial due to its excellent biocompatibility, exceptional mech. properties, tunable degrdn., ease of processing, and sufficient supply. As a material with excellent processability, SF can be processed into various forms with different structures, including particulate, fiber, film, and three-dimensional (3D) porous scaffolds. This review discusses and summarizes the various constructions of SF-based materials, from single structures to multi-level structures, and their applications. In combination with single structures, new techniques for creating special multi-level structures of SF-based materials, such as micropatterning and 3D-printing, are also briefly addressed.
- 98Kaewpirom, S.; Boonsang, S. Influence of alcohol treatments on properties of silk-fibroin-based films for highly optically transparent coating applications. RSC Adv. 2020, 10, 15913– 15923, DOI: 10.1039/D0RA02634D98https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXnsFSruro%253D&md5=b9c932186edd61aea6af504fe343a036Influence of alcohol treatments on properties of silk-fibroin-based films for highly optically transparent coating applicationsKaewpirom, Supranee; Boonsang, SiridechRSC Advances (2020), 10 (27), 15913-15923CODEN: RSCACL; ISSN:2046-2069. (Royal Society of Chemistry)Thin films of silk fibroin were prepd. by solvent evapn. from calcium chloride/ethanol aq. soln. The influence of alc. treatments on thermal, mech. and optical properties of silk-fibroin-based film is presented. To understand the conformal structure of the alc.-treated silk fibroin film, the IR spectral decompn. method is employed. The optical properties esp. the optical transparency, haze and fluorescence emission of alc.-treated silk fibroin film is systematically investigated together with the conformal structure to understand the effect of the fibril such as the beta-sheet influencing the optical properties. Monohydric alc. treatment increased beta-turn content in the regenerated silk fibroin structure. The ethanol-treated silk-fibroin films displayed a distinct interference of oscillating crests and troughs in the UV-Vis transmittance spectra, thereby showing the lowest optical haze of 2.56%. In contrast, the silk-fibroin films treated with methanol and propanol exhibit the highest (14.17%) and second-highest (10.29%) optical transmittance haze, resp. These results show the relationship between the beta-turn content and optical haze properties. The results manifestly provide a method to manuf. exceptional optically transparent silk-fibroin films with adjustable light diffusion and scattering which can be designed to meet specific applications with the potential to provide UV-shielding protection via monohydric alc. treatment.
- 99Parker, W. A. Alcohol-containing pharmaceuticals. Am. J. Drug Alcohol. Ab. 1982, 9, 195– 209, DOI: 10.3109/00952998209002622There is no corresponding record for this reference.
- 100Liquid Medicine May Contain a High Level of Alcohol. Use with Caution When Administering to a Child; ConsumerMedSafety (Accessed July 2021).There is no corresponding record for this reference.
- 101Medications Containing Alcohol - A Resource Sheet, rbhmonitoring.com/Content/Oregon/Resources/Medications%20Containing%20Alcohol%20and%20Options%20Without%20Alcohol.pdf (Accessed June 2021).There is no corresponding record for this reference.
- 102Marelli, B.; Patel, N.; Duggan, T.; Perotto, G.; Shirman, E.; Li, C. M.; Kaplan, D. L.; Omenetto, F. G. Programming function into mechanical forms by directed assembly of silk bulk materials. P. Natl. Acad. Sci. 2017, 114, 451– 456, DOI: 10.1073/pnas.1612063114There is no corresponding record for this reference.
- 103Jeong, L.; Lee, K. Y.; Liu, J. W.; Park, W. H. Time-resolved structural investigation of regenerated silk fibroin nanofibers treated with solvent vapor. Int. J. Biol. Macromol. 2006, 38, 140– 144, DOI: 10.1016/j.ijbiomac.2006.02.009103https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD28Xjs1yntro%253D&md5=2cc5a3b49fb01ff794bad95df78a253bTime-resolved structural investigation of regenerated silk fibroin nanofibers treated with solvent vaporJeong, Lim; Lee, Kuen Yong; Liu, Ju Whan; Park, Won HoInternational Journal of Biological Macromolecules (2006), 38 (2), 140-144CODEN: IJBMDR; ISSN:0141-8130. (Elsevier B.V.)Nonwoven matrixes of silk fibroin (SF) nanofibers were prepd. by electrospinning a regenerated SF soln., followed by treatment with solvent vapor including water, methanol, ethanol, and propanol. Structural changes of solvent vapor-treated SF nanofibers were investigated in a time-resolved manner using IR spectroscopy. Conformational transitions of SF nanofibers from random coil to β-sheet forms were dependent on the type of solvent vapor used, and their transition rates were strongly influenced by treatment temps. Consistent with previous findings, methanol vapor treatment provided a fast and effective means by which to alter the secondary structure of SF nanofibers. However, treatment with water vapor, as compared to treatment with alc. vapor, was also useful for inducing structural changes in SF nanofibers. As demonstrated in the present study, our approach of controlling secondary structure formation of proteins by solvent vapor treatment and monitoring real-time conformational changes may be useful for the design and tailoring of materials for biomedical applications.
- 104Dubey, P.; Chowdhury, P. K.; Ghosh, S. Modulation of Aggregation of Silk Fibroin by Synergistic Effect of the Complex of Curcumin and Beta-Cyclodextrin. BBA-Proteins Proteom. 2019, 1867, 416– 425, DOI: 10.1016/j.bbapap.2019.01.009There is no corresponding record for this reference.
- 105Preneel, B. Cryptographic hash functions. Eur. T. Telecommun. 1994, 5, 431– 448, DOI: 10.1002/ett.4460050406There is no corresponding record for this reference.
- 106Sagar, F. A. Cryptographic Hashing Functions - MD5 , thesis, 2016; pp 1– 9. https://cs.indstate.edu/~fsagar/doc/paper.pdfThere is no corresponding record for this reference.
- 107Lachenmeier, D. W.; Neufeld, M.; Rehm, J. The impact of unrecorded alcohol use on health: What do we know in 2020?. J. Stud. Alcohol Drugs 2021, 82, 28– 41, DOI: 10.15288/jsad.2021.82.28107https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BB3snivFyqug%253D%253D&md5=6cee6417ce0c92a36a119052d4073486The Impact of Unrecorded Alcohol Use on Health: What Do We Know in 2020?Lachenmeier Dirk W; Neufeld Maria; Neufeld Maria; Rehm Jurgen; Neufeld Maria; Rehm Jurgen; Rehm Jurgen; Rehm Jurgen; Rehm Jurgen; Rehm Jurgen; Rehm Jurgen; Rehm JurgenJournal of studies on alcohol and drugs (2021), 82 (1), 28-41 ISSN:.OBJECTIVE: About 25% of global alcohol consumption is unrecorded, that is, concerns alcohol not registered in the country where it is consumed. Unrecorded alcohol includes homemade, illicit, or surrogate alcohols. The aim of this review is to update the evidence on unrecorded alcohol and its impact on health. METHOD: A narrative review and qualitative synthesis of scientific literature (English and Russian) for the period 2016-2020 was conducted. RESULTS: A total of 100 articles were included in the synthesis. The most harm because of unrecorded alcohol seems to be caused by ethanol, although single and mass methanol poisonings constitute exceptions. Nevertheless, unrecorded consumption is associated with disproportionate harm that goes beyond toxicity, which is linked to hazardous drinking patterns of unrecorded alcohol, and its association with alcohol use disorders and social marginalization. The online sale of unrecorded alcohol, which circumvents alcohol availability regulations, is an emerging and not yet well-explored issue. CONCLUSIONS: Policy options include restricting access to methanol, increasing taxation, denaturing ethanol-containing liquids that could be used as surrogates, introducing more effective and less toxic denaturizing additives, and improving monitoring systems for fraud, tax evasion, and local sales restrictions, including raising the minimum legal drinking age. These measures should be implemented within a holistic policy framework to avoid unintended effects, such as an increase in total alcohol consumption, shifts from certain types of unrecorded products to potentially toxic alternatives, or limiting economic activity and jeopardizing the livelihoods of vulnerable populations (e.g., women comprise the majority of those making homebrew in some countries).
- 108McKee, M.; Adany, R.; Leon, D. A. Illegally produced alcohol. Br. Med. J. 2012, 344, e1146 DOI: 10.1136/bmj.e1146There is no corresponding record for this reference.
- 109Spencer, J.; Lord, N.; Benson, K.; Bellotti, E. ‘C’ is for commercial collaboration: Enterprise and structure in the ‘middle market’ of counterfeit alcohol distribution. Crime Law Soc. Change 2018, 70, 543– 560, DOI: 10.1007/s10611-018-9781-zThere is no corresponding record for this reference.
- 110Counterfeit Goods in the Uk, Who Is Buying What, and Why; pwc.co.uk, October, 2013; p 2.There is no corresponding record for this reference.
- 111Scotch Whisky Economic Impact Report 2018; Scotch Whisky Association, scotch-whisky.org.uk/newsroom/scotch-whisky-economic-impact-report-2018 (Accessed July 20210.There is no corresponding record for this reference.
- 112Breg, J. M.; Tymoczko, J. L.; Stryer, L. Section 23.1 Proteins Are Degraded to Amino Acids; Biochemistry, W. H. Freeman: New York, USA, 2002.There is no corresponding record for this reference.
- 113Hamuro, Y.; Coales, S. J.; Molnar, K. S.; Tuske, S. J.; Morrow, J. A. Specificity of Immobilized Porcine Pepsin in H/D Exchange Compatible Conditions. Rapid Commun. Mass Spectrom. 2008, 22, 1041– 1046, DOI: 10.1002/rcm.3467113https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1cXksFWku7Y%253D&md5=8a3b158c0922c0a28ac01201a76f1ba8Specificity of immobilized porcine pepsin in H/D exchange compatible conditionsHamuro, Yoshitomo; Coales, Stephen J.; Molnar, Kathleen S.; Tuske, Steven J.; Morrow, Jeffrey A.Rapid Communications in Mass Spectrometry (2008), 22 (7), 1041-1046CODEN: RCMSEF; ISSN:0951-4198. (John Wiley & Sons Ltd.)Statistical anal. of data from 39 proteins (13,766 amino acid residues) digested with immobilized porcine pepsin under conditions compatible with hydrogen/deuterium (H/D) exchange (<1°, <30 s) was performed to examine pepsin cleavage specificity. The cleavage of pepsin was most influenced by the amino acid residue at position P1. Phe and Leu are favored residues each with a cleavage probability greater than 40%. His, Lys, Arg, or Pro residues prohibit cleavage when found at the P1 position. Pro also cannot be at position P2 (cleavage probability <0.3%). Occupation of the P3 position by His, Lys, or Arg, or occupation of the P2' position by Pro, also leads to very little cleavage (cleavage probability <1.7%). The av. cleavage probability over the entire data set was 13.6%, which is slightly lower than the value previously obtained by J. C. Powers et al. (14.8%). This is due, in part, to the larger protein sizes used in the current study. While the specificity of pepsin was similar to that previously obsd., higher selectivity was obsd. in the present study due to less exptl. variation in the conditions used to generate the authors' database.
- 114Rick, W. Trypsin. In Methods of Enzymatic Analysis; Bergmeyer, J. B. H. U., Grabl, M., Eds.; Verlag Chemie GmbH: Weinheim, Germany, 1974, Vol. 2.There is no corresponding record for this reference.
- 115Li, X. Q.; Zhang, G. H.; Ngo, N.; Zhao, X. N.; Kain, S. R.; Huang, C. C. Deletions of the aequorea victoria green fluorescent protein define the minimal domain required for fluorescence. J. Biol. Chem. 1997, 272, 28545– 28549, DOI: 10.1074/jbc.272.45.28545115https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaK2sXntlCku7s%253D&md5=6efdfdd0b9f5406b04f66d9cd1e42638Deletions of the Aequorea victoria green fluorescent protein define the minimal domain required for fluorescenceLi, Xianqiang; Zhang, Guohong; Ngo, Nhatanh; Zhao, Xiaoning; Kain, Steven R.; Huang, Chiao-ChainJournal of Biological Chemistry (1997), 272 (45), 28545-28549CODEN: JBCHA3; ISSN:0021-9258. (American Society for Biochemistry and Molecular Biology)The Green Fluorescent Protein (GFP) from the jellyfish, A. victoria, is a widely used marker for gene expression and protein localization studies. Dissection of the structure of the protein would be expected to shed light on its potential applications to other fields such as the detection of protease activity. Using deletion anal., the authors defined the minimal domain in GFP required for fluorescence to amino acids 7-229. This domain starts at the middle of the 1st small α-helix at the N-terminus of GFP and ends immediately following the last β-sheet. Studies of the amino acids at both termini of the minimal domain revealed that positions 6 and 7 at the N-terminus were Glu-specific. Change of the Glu residues to other amino acids resulted in redn. of GFP fluorescence. Position 229 at the C-terminus of GFP, however, was nonspecific; the Ile could be replaced with other amino acids with no measurable loss of fluorescence. A total of only 15 terminal amino acids could be deleted from GFP without disrupting fluorescence, consistent with findings of a previous study of GFP crystal structure that a tightly packed structure exists in the protein. The authors also generated internal deletions within the loop regions of GFP according to its crystal structure and found that all such deletions eliminated GFP fluorescence.
- 116Patterson, G. H.; Knobel, S. M.; Sharif, W. D.; Kain, S. R.; Piston, D. W. Use of the green fluorescent protein and its mutants in quantitative fluorescence microscopy. Biophys. J. 1997, 73, 2782– 2790, DOI: 10.1016/S0006-3495(97)78307-3116https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaK2sXntF2hsLo%253D&md5=166ab34b861ba1fe81bc8549f3002727Use of the green fluorescent protein and its mutants in quantitative fluorescence microscopyPatterson, George H.; Knobel, Susan M.; Sharif, Wallace D.; Kain, Steven R.; Piston, David W.Biophysical Journal (1997), 73 (5), 2782-2790CODEN: BIOJAU; ISSN:0006-3495. (Biophysical Society)We have investigated properties relevant to quant. imaging in living cells of five green fluorescent protein (GFP) variants that have been used extensively or are potentially useful. We measured the extinction coeffs., quantum yields, pH effects, photobleaching effects, and temp.-dependent chromophore formation of wtGFP, αGFP (F99S/M153T/V163A), S65T, EGFP (S64L/S65T), and a blue-shifted variant, EBFP (F64L/S65T/Y66H/Y145F). Absorbance and fluorescence spectroscopy showed little difference between the extinction coeffs. and quantum yields of wtGFP and αGFP. In contrast, S65T and EGFP extinction coeffs. made them both ∼6-fold brighter than wtGFP when excited at 488 nm, and EBFP absorbed more strongly than the wtGFP when excited in the near-UV wavelength region, although it had a much lower quantum efficiency. When excited at 488 nm, the GFPs were all more resistant to photobleaching than fluorescein. However, the wtGFP and αGFP photobleaching patterns showed initial increases in fluorescence emission caused by photoconversion of the protein chromophore. The wtGFP fluorescence decreased more quickly when excited at 395 nm than 488 nm, but it was still more photostable than the EBFP when excited at this wavelength. The wtGFP and αGFP were quite stable over a broad pH range, but fluorescence of the other variants decreased rapidly below pH 7. When expressed in bacteria, chromophore formation in wtGFP and S65T was found to be less efficient at 37° than at 28°, but the other three variants showed little differences between 37° and 28°. In conclusion, no single GFP variant is ideal for every application, but each one offers advantages and disadvantages for quant. imaging in living cells.
- 117Malik, A.; Rudolph, R.; Sohling, B. Use of enhanced green fluorescent protein to determine pepsin at high sensitivity. Analyt. Biochem. 2005, 340, 252– 258, DOI: 10.1016/j.ab.2005.02.022117https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD2MXjtlWqtLs%253D&md5=c7439731cd231c8375ddc5a9da262886Use of enhanced green fluorescent protein to determine pepsin at high sensitivityMalik, Ajamaluddin; Rudolph, Rainer; Soehling, BrigitteAnalytical Biochemistry (2005), 340 (2), 252-258CODEN: ANBCA2; ISSN:0003-2697. (Elsevier)A fluorometric assay for pepsin and pepsinogen was developed using enhanced green fluorescent protein (EGFP) as a substrate. Acid denaturation of EGFP resulted in a complete loss of fluorescence that was completely reversible on neutralization. In the proteolytic assay procedure, acid-denatured EGFP was digested by pepsin or activated pepsinogen. After neutralization, the remaining amt. of undigested EGFP refolded and was detd. by fluorescence. Under std. digestion conditions, 4.8-24.0 ng pepsin or pepsinogen was used. Using porcine pepsin as a std., 38 ± 6.7 ng EGFP was digested per min/ng pepsin. Activated porcine pepsinogen revealed a similar digestion rate (37.2 ± 5.2 ng EGFP/min/ng activated pepsinogen). The sensitivity of the proteolysis assay depended on the time of digestion and the temp. Increasing the temp. and incubation time allowed quantification of pepsin or pepsinogen in a sample even in the picogram range. The pepsin-catalyzed EGFP digestion showed typical Michaelis-Menten kinetics. The Km and Vmax values were detd. for pepsin and activated pepsinogen. Digestion of EGFP by pepsin revealed distinct cleavage sites, as analyzed by SDS-PAGE.
- 118Mares, R. E.; Melendez-Lopez, S. G.; Ramos, M. A. Acid-denatured green fluorescent protein (GFP) as model substrate to study the chaperone activity of protein disulfide isomerase. Int. J. Mol. Sci. 2011, 12, 4625– 4636, DOI: 10.3390/ijms12074625118https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXhtVWqs73O&md5=08cf9db37efb6adc1cc6ee949ebb84dbAcid-denatured green fluorescent protein (GFP) as model substrate to study the chaperone activity of protein disulfide isomeraseMares, Rosa E.; Melendez-Lopez, Samuel G.; Ramos, Marco A.International Journal of Molecular Sciences (2011), 12 (), 4625-4636CODEN: IJMCFK; ISSN:1422-0067. (MDPI AG)Green fluorescent protein (GFP) has been widely used in several mol. and cellular biol. applications, since it is remarkably stable in vitro and in vivo. Interestingly, native GFP is resistant to the most common chem. denaturants; however, a low fluorescence signal has been obsd. after acid-induced denaturation. Furthermore, this acid-denatured GFP has been used as substrate in studies of the folding activity of some bacterial chaperones and other chaperone-like mols. Protein disulfide isomerase enzymes, a family of eukaryotic oxidoreductases that catalyze the oxidn. and isomerization of disulfide bonds in nascent polypeptides, play a key role in protein folding and it could display chaperone activity. However, contrasting results have been reported using different proteins as model substrates. Here, we report the further application of GFP as a model substrate to study the chaperone activity of protein disulfide isomerase (PDI) enzymes. Since refolding of acid-denatured GFP can be easily and directly monitored, a simple micro-assay was used to study the effect of the mol. participants in protein refolding assisted by PDI. Addnl., the effect of a well-known inhibitor of PDI chaperone activity was also analyzed. Because of the diversity their functional activities, PDI enzymes are potentially interesting drug targets. Since PDI may be implicated in the protection of cells against ER stress, including cancer cells, inhibitors of PDI might be able to enhance the efficacy of cancer chemotherapy; furthermore, it has been demonstrated that blocking the reductive cleavage of disulfide bonds of proteins assocd. with the cell surface markedly reduces the infectivity of the human immunodeficiency virus. Although several high-throughput screening (HTS) assays to test PDI reductase activity have been described, we report here a novel and simple micro-assay to test the chaperone activity of PDI enzymes, which is amenable for HTS of PDI inhibitors.
- 119Zhang, Y. Y.; Zhao, Y. L.; Song, B.; Liu, K. M.; Gu, J. M.; Yue, Y. Y.; Xiong, R. H.; Huang, C. B. UV-fluorescence probe for detection Ni2+ with colorimetric/spectral dual-mode analysis method and its practical application. Bioorg. Chem. 2021, 114, 105103, DOI: 10.1016/j.bioorg.2021.105103119https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3MXhsVWhsbzI&md5=a882f5aa879ed9e8858d2d724f312665UV-fluorescence probe for detection Ni2+ with colorimetric/spectral dual-mode analysis method and its practical applicationZhang, Yingying; Zhao, Yanliang; Song, Bo; Liu, Kunming; Gu, Jiamin; Yue, Yiying; Xiong, Ranhua; Huang, ChaoboBioorganic Chemistry (2021), 114 (), 105103CODEN: BOCMBM; ISSN:0045-2068. (Elsevier B.V.)Fluorescence probe combines with fluorescence imaging technol. has become the most powerful anal. method with their great advantages of high sensitivity and selectivity and real-time monitoring. Ni2+ is widely distributed in food, environment and living animals, thereof, it is of great significance for detection Ni2+ with high selectivity. Herein, a simple strategy is proposed to design and synthesiz a small mol. fluorescent probe Y1 by using "one-pot" method. The spectroscopic behaviors including UV-Vis absorption and fluorescence emission spectrum have been used to verify the feasibility of probe towards Ni2+ in water/EtOH (vol./vol. = 2:8) mixts. under neutral condition. As expected, Y1 offers high selectivity and sensitivity for detection Ni2+ in aq. soln. with a good linear relationship and low detection limit within Ni2+ concn. variation from 0 to 13 μM (DOL = 0.0038 μM, R2 = 0.9983). It is remarkable that Y1 can be applied for real-time visualization Ni2+ change in sprouted potato and zebrafish with great photo-stability, highlighting that the practicability and feasibility of Y1 to detect and monitor Ni2+ in the field of food industry and biomedical field.
- 1206.15 lighting. U.S. General Services Administration, gsa.gov/node/82715 (Accessed January 2022).There is no corresponding record for this reference.
- 121Kim, S. W.; Yun, E. Y.; Choi, K. H.; Kim, S. R.; Kang, S. W.; Park, S. W.; Goo, T. W. Utilization of the Bombyx mori heat shock protein 70 promoter for screening transgenic silkworms. Entomolog.l Res. 2013, 43, 282– 287, DOI: 10.1111/1748-5967.12031There is no corresponding record for this reference.
- 122Nagy, A.; Malnasi-Csizmadia, A.; Somogyi, B.; Lorinczy, D. Thermal stability of chemically denatured green fluorescent protein (GFP) - A preliminary study. Thermochim. Acta 2004, 410, 161– 163, DOI: 10.1016/S0040-6031(03)00397-6122https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD3sXpvFGhtLo%253D&md5=8a1a3cb6caa84f1db2f0b9e750662e1aThermal stability of chemically denatured green fluorescent protein (GFP). A preliminary studyNagy, Attila; Malnasi-Csizmadia, Andras; Somogyi, Bela; Lorinczy, DenesThermochimica Acta (2004), 410 (1-2), 161-163CODEN: THACAS; ISSN:0040-6031. (Elsevier Science B.V.)Green fluorescent protein (GFP) is a light emitter in the bioluminescence reaction of the jellyfish, Aequorea victoria. GFP consists of 238 amino acids and produces green fluorescent light (λmax = 508 nm), when irradiated with near-UV light. The fluorescence is due to the presence of a chromophore consisting of an imidazolone ring, formed by a post-translational modification of the tripeptide, -Ser65-Tyr66-Gly67-, which is buried in the β-barrel. GFP is an extremely compact and thermostable mol. Here, the authors present data for the effect of the chem. denaturing agent, guanidine-HCl (GuHCl), on the thermostability of GFP. When GuHCl was applied, the global thermostability and the melting temp. (Tm) of GFP decreased, and was monitored by DSC. The results indicated that in 1-6M concn. range of GuHCl, the Tm decreased continuously from 83 to 38°. An interesting finding was that the calcd. enthalpy (ΔH) decreased with GuHCl concn. up to 3M (5.6-0.2 kJ/mol), but at 4M GuHCl it jumped to 8.4, and at higher GuHCl concns. it fell to 1.1 kJ/mol. The 1st phenomenon, i.e., the decrease of the Tm with increasing GuHCl concn., could be easily explained by the effect of the extended chem. denaturation when lesser amts. of heat were required to diminish the remaining H-bonds in the β-barrel. The surprising increase in ΔH at 4M GuHCl could be the consequence of dimerization or formation of a stable complex between GFP and the denaturing agent as well as pptn. at an extreme GuHCl concn. The authors plan further expts. to elucidate the fluorescent consequence of these processes.
- 123Alkaabi, K. M.; Yafea, A.; Ashraf, S. S. Effect of pH on thermal- and chemical-induced denaturation of gfp. Appl. Biochem. Biotechnol. 2005, 126, 149– 156, DOI: 10.1385/ABAB:126:2:149123https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD2MXhtVWksr3F&md5=c1441d308b9f978d7836b75f75688efdEffect of pH on thermal- and chemical-induced denaturation of GFPAlkaabi, Klaithem M.; Yafea, Abeer; Ashraf, S. SalmanApplied Biochemistry and Biotechnology (2005), 126 (2), 149-156CODEN: ABIBDL; ISSN:0273-2289. (Humana Press Inc.)Green fluorescent protein (GFP) is an unusually stable autofluorescent protein that is increasingly being exploited for many applications. In this report, we have used fluorescence spectroscopy to study the effect of pH on the denaturation of GFP with sodium dodecyl sulfate (SDS), urea, and heat. Surprisingly, SDS (up to 0.5%) did not have any significant effect on the fluorescence of GFP in pH 7.5 or 8.5 buffers; however, at pH 6.5, the protein lost all fluorescence within 1 min of incubation. Similarly, incubation of GFP with 8 M urea at 50°C resulted in time-dependent denaturation of GFP, but only in pH 6.5 buffer. At higher pH values (pH 7.5 and pH 8.5), GFP was quite stable in 8 M urea at 50°C, showing only a slight decrease in fluorescence. Heat denaturation of GFP was found to be pH-dependent as well, with the denaturation being fastest at pH 6.5 as compared to pH 7.5 or pH 8.5. Like the denaturation studies, renaturation of heat-denatured GFP was most efficient at pH 8.5, followed by pH 7.5, and then pH 6.5. These results suggests that GFP undergoes a structural/stability shift between pH 6.5 and pH 7.5, with the GFP structure at pH 6.5 being very sensitive to denaturation by SDS, urea, and heat.
- 124Rockwood, D. N.; Preda, R. C.; Yucel, T.; Wang, X. Q.; Lovett, M. L.; Kaplan, D. L. Materials fabrication from Bombyx mori silk fibroin. Nat. Protoc. 2011, 6, 1612– 1631, DOI: 10.1038/nprot.2011.379124https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXht1CrsbzN&md5=f073189b8c31ae54201228efb0d66eaeMaterials fabrication from Bombyx mori silk fibroinRockwood, Danielle N.; Preda, Rucsanda C.; Yucel, Tuna; Wang, Xiao-Qin; Lovett, Michael L.; Kaplan, David L.Nature Protocols (2011), 6 (10), 1612-1631CODEN: NPARDW; ISSN:1750-2799. (Nature Publishing Group)Silk fibroin, derived from Bombyx mori cocoons, is a widely used and studied protein polymer for biomaterial applications. Silk fibroin has remarkable mech. properties when formed into different materials, demonstrates biocompatibility, has controllable degrdn. rates from hours to years and can be chem. modified to alter surface properties or to immobilize growth factors. A variety of aq. or org. solvent-processing methods can be used to generate silk biomaterials for a range of applications. In this protocol, the authors include methods to ext. silk from B. mori cocoons to fabricate hydrogels, tubes, sponges, composites, fibers, microspheres and thin films. These materials can be used directly as biomaterials for implants, as scaffolding in tissue engineering and in vitro disease models, as well as for drug delivery.
Supporting Information
Supporting Information
The Supporting Information is available free of charge at https://pubs.acs.org/doi/10.1021/acscentsci.1c01233.
Experimental details including materials, chemicals, methods, and characterization; supplemental figures including transgenic silkworms and silk glands, fabrication procedure of edible matrix codes, optical properties of micrograting patterned silk fibroin films, edible matrix codes with different matrix sizes, photostability of fluorescent silk fibroin films under alcohol treatments, square units for constructing synthetic edible matrix codes, augmented fluorescence images of edible matrix codes (7 × 7) and binary output key extraction, cryptographic key generation of edible 5 × 5 and 9 × 9 matrix codes, possible quaternary and double binary keys, smartphone reader with optical filters, and stability of silk fibroin films immersed in high-value alcoholic spirits, and photostability, thermal stability, and long-term reliability of edible matrix codes; supplemental table including the 2D CNN model information for key extraction (PDF)
Movie S1: Simulated on-dose authentication of a solid oral-dosage form (e.g., pill, tablet, or capsule) using a smartphone (AVI)
Movie S2: Simulated in-dose authentication of a high-value alcoholic spirit using a smartphone (AVI)
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