Water scarcity, contamination, and lack of sanitation are global issues that require innovations in chemistry, engineering, and materials science. To tackle the challenge of providing high-quality drinking water for a growing population, we need to develop high-performance and multifunctional materials to treat water on both small and large scales. As modern society and science prioritize more sustainable engineering practices, water treatment processes will need to use materials produced from sustainable resources via green chemical routes, combining multiple advanced properties such as high surface area and great affinity for contaminants. Lignin, one of the major components of plants and an abundant byproduct of the cellulose and bioethanol industries, offers a cost-effective and scalable platform for developing such materials, with a wide range of physicochemical properties that can be tailored to improve their performance for target water treatment applications. This review aims to bridge the current gap in the literature by exploring the use of lignin, both as solid bulk or solubilized macromolecules and nanolignin as multifunctional (nano)materials for sustainable water treatment processes. We address the application of lignin-based macro-, micro-, and nanostructured materials in adsorption, catalysis, flocculation, membrane filtration processes, and antimicrobial coatings and composites. Throughout the exploration of recent progress and trends in this field, we emphasize the importance of integrating principles of green chemistry and materials sustainability to advance sustainable water treatment technologies.

Natural halloysite clay nanotubes with a 50 nm diameter and a 15 nm inner lumen have recently been explored for numerous medical applications. Due to the tubular morphology and biocompatibility of halloysite, this material can serve as a suitable container for drugs and proteins, allowing their controlled and sustained release over a period ranging from days to weeks. The discovery that it is possible to load a halloysite clay nanotube’s inner lumen cavity with a bioactive species has prompted its consideration for pharmaceutical and cosmetic utilization. Additionally, the different chemical compositions of the inner and outer tube surfaces (formed by Al₂O₃ and SiO₂ groups and of opposite electric charge) enable halloysite to be suitable for the selective (internal or external) adsorption of medical agents. First, we describe the fabrication of nanoclay skincare products and the detection of harmful compounds in creams. Next, the use of halloysite for reinforcing, protecting, and coloring human hair is considered. An in-depth review of the self-assembly of nanotubes for haircare related purposes is offered; we note how the nanotubes can be loaded with dyes, drugs, and keratin and create a 1–2 μm hair surface coating with coloring, UV protection capacity, or antiparasitic actions which can be preserved even after several shampoo washes. Halloysite Pickering emulsification can serve as an efficient tool for producing cosmetic creams with higher stability and reduced irritation effects, as compared with traditional surfactant-based emulsions; this is accomplished when the clay nanotubes form a stabilizing interlayer that encapsulates oil microbubbles in water. The emulsifying action of clay nanotubes makes the formulations suitable for use with cosmetic waxes and vegetable oils, which are capable of carrying water insoluble vitamins. It is expected that these uses of halloysite Pickering emulsions for cosmetic and topical drug delivery will increase with time, just as their uses in other fields have, including digestive diseases, blood coagulants, environmental remediation, and cultural heritage areas (such as the conservation of ancient bones and wood).

Injectable hydrogels represent a highly promising approach for localized drug delivery systems (DDSs) in the management of bone-related conditions such as osteoporosis, osteonecrosis, osteoarthritis, osteomyelitis, and osteosarcoma. Their appeal lies in their biocompatibility, adjustable mechanical properties, and capacity to respond to external stimuli, including pH, temperature, light, redox potential, ionic strength, and enzymatic activity. These features enable enhanced targeted delivery of bioactive agents. This mini-review evaluates the synthesis of injectable hydrogels as well as recent advancements for treating a range of bone disorders, focusing on their mechanisms as localized and sustained DDSs for delivering drugs, nanoparticles, growth factors, and cells (e.g., stem cells). Moreover, it highlights their clinical studies for bone disease treatment. Additionally, it emphasizes the potential synergy between injectable hydrogels and hydrogel-based point-of-care technologies, which are anticipated to play a pivotal role in the future of bone disease therapies. Injectable hydrogels have the potential to transform bone disease treatment by facilitating precise, sustained, and minimally invasive therapeutic delivery. Nevertheless, significant challenges, including long-term biocompatibility, scalability, reproducibility, and precise regulation of drug release kinetics, must be addressed to unlock their clinical potential fully. Addressing these challenges will not only advance bone disease therapy but also open new avenues in regenerative medicine and personalized healthcare.

Cancer affects millions of individuals every year and is the second most common cause of death. Various therapeutic strategies are explored for the management of cancer including radiation therapy and chemotherapy with or without surgical procedures. However, the drawbacks like poor cancer cell targeting and higher toxicity for healthy cells need the advancement of the therapeutic strategy. The exploration of nanomedicine achieves targeted distribution, and the adoption of microfluidics technology for the preparation of the nanoparticulate system has enhanced the efficacy and uniformity of the nanocarriers. The overview of the existing designs of the microfluidics device assisted in the preparation of the nanoparticles, and various nanodelivery systems formulated using the microfluidic device including liposomes, lipidic nanocarriers, quantum dots, polymeric nanoparticles, and metallic nanocarriers are discussed in this review. Further, the challenges associated with the fabrication of the microfluidics device and the fabrication of microfluidics device-based nanoparticles are detailed here.

Artificial photosynthetic biohybrid systems possess the remarkable ability not only to convert solar energy into chemical energy but also to store this energy in the form of organic matter. By leveraging this system, we hold the promise of achieving sustainable energy utilization and chemical production. This review comprehensively summarizes artificial photosynthetic biohybrid systems consisting of metal sulfides, noble metals, quantum dots, composite photocatalysts, and conjugated polymers of organic semiconductor materials with microorganisms and provides a comprehensive overview of examples of artificial photosynthetic biohybrid systems converting CO₂ into high-value compounds and a summary of the relevant devices that are currently available. Additionally, the review discusses the challenges and future development trends related to artificial photosynthetic biohybrid systems.

In-situ fabrication of nucleic acid molecular machines in biological environments is desirable for smart theranostic applications. However, given the complex nature of biological environments, the integration of multiple functional modules into a coordinated machine remains challenging. Recent advances in nucleic acid nanotechnology offer solutions to these challenges. Here, we outline design principles for nucleic acid–based molecular machines tailored for physiological conditions, drawing on recent examples. We review cutting-edge technologies that facilitate their functionalization in physiological settings, particularly presynthesis modifications using unnatural bases and postsynthesis functionalization via bioorthogonal chemistry and noncovalent biological interactions. We discuss the advantages and limitations of these technologies and suggest future directions to overcome existing challenges.

The encapsulation of bacteria in metal–organic frameworks (MOFs) is being studied for use in biomedicine and bioremediation. However, biocompatibility could be improved, as much of the research focuses on ZIF-8 and Escherichia coli. MIL-88A, composed of fumaric acid and iron, offers a safer alternative. This study investigates encapsulation of the probiotic strain Lactiplantibacillus plantarum 299v in a nanocrystalline matrix via a simple one-pot synthesis. The encapsulated bacteria show improved stability in saline, lysozyme and pepsin compared to uncoated cells. These findings highlight the potential of the iron(III) fumarate matrix for bacterial protection and controlled release for biological applications.

Oxygen anions (superoxide and peroxide anions) are naturally unstable and prone to chemical interactions. These reactive oxygen species (ROS) are formed during long-term storage in olive oil (OO), the structural properties of which extend the ROS lifespan more effectively than those of other vegetable oils. In wound treatment, superoxide anions serve as precursors for hydrogen peroxide and play a crucial role in cell proliferation, migration, and angiogenesis. These anions were encapsulated within the OO medium for crystallization. Piezoelectric actuators were employed to distribute the trapped bubbles evenly throughout the crystallized OO. The ROS-filled OO microcapsules eliminated volatile organic compounds and particulate matter (from the air). Samples stored in crystallized OO were utilized to investigate the antibacterial effects. Both Escherichia coli and Staphylococcus aureus were implicated in skin infections (with S. aureus as the primary pathogen and E. coli as the secondary pathogen) and were selected for antibacterial testing. Microcapsules applied to cultured E. coli and S. aureus resulted in different inhibition zones. Two groups [control (C-) and treatment (T-)] of second-degree burn wounds were created on the dorsal area of 15 Wistar rats. Over a period of 2 weeks, statistical analysis using a t-test demonstrated a significant reduction in the wound size in the T-zones. Histological examination with hematoxylin, eosin, and trichrome staining of tissue samples from the wound areas revealed a notable reduction in inflammation, enhanced epidermal cell proliferation, improved activity in producing hair follicles, and increased collagen deposition in the treated regions on different days of observation.

An intricate biochemical system of coordinated cellular reactions is involved in restoring damaged tissue after wounds. In chronic wounds, such as diabetic foot ulcers, poor angiogenesis is a common stumbling block due to elevated glucose levels, increased proteolytic enzyme activity, and decreased production of growth factors. While various strategies, including modulation of inflammatory cells, administration of growth factors, and therapies involving stem cells or genes, have been explored to promote angiogenesis, they often suffer from limitations such as poor biodistribution, immunological rejection, administration/dosing, and proteolytic instability. Glycosaminoglycans, such as heparan sulfate, facilitate growth factor interactions with their receptors to induce angiogenic signaling, but their exogenous administration is hindered by poor stability, low serum half-life, and immunogenicity. Cyclic peptides, known for their structural stability and specificity, offer a promising alternative for inducing angiogenesis upon functional modifications. In this work, we developed heparan sulfate (HS)-mimetic cyclic peptide nanotubes (CPNTs) grafted with bioactive groups to enhance angiogenesis without using exogenous growth factors, drugs, or supplements. These CPNTs incorporate glutamic acid, serine, and sulfonated lysine to mimic the functional groups in heparin. The sulfonated cyclic hexapeptide nanotubes developed from ^DPro-^LTrp-^DLeu-^LSer-^DGlu-^LLys demonstrated significant proangiogenic activity in HUVECs under hyperglycemic conditions; enhanced endothelial cell motility, invasion, and tube formation; and upregulation of proangiogenic genes and proteins. These HS-mimicking nanotubes have shown a strong potential for promoting impaired angiogenesis, without incorporating exogenous growth factors, and show strong potential in treating diabetic wounds. To the best of our knowledge, this is the first report on the use of HS-mimetic proangiogenic cyclic peptide nanotubes for diabetic wound healing.

In the current study, we developed a controlled drug delivery system using a polymeric matrix composed of biopolymer poly(vinylidene fluoride) (PVDF) and ciprofloxacin (CPF)-loaded titanium (Ti) nanotubes (TNTs) on Ti substrates for biomedical applications. The TNT arrays over the Ti surface were obtained through an anodization route. The PVDF coatings were dip-coated on TNT-Ti loaded with CPF. The chemical, microstructure, and surface properties of the TNTs and coated surfaces were characterized using FTIR, XRD, transmission electron microscopy (TEM), scanning electron microscopy (SEM)/energy-dispersive X-ray spectroscopy (EDS), and surface hydrophilicity analyses. The performance of the implant surfaces was evaluated through in vitro corrosion studies in simulated body fluid (SBF), biocompatibility with MG63 cells, and antibacterial properties. The results revealed that the PVDF/0.1CPF coatings exhibited sustained release of CPF from the polymer matrix at a linear rate and releasing profile for 168 h. PVDF/0.1CPF coating showed decreased corrosion current density (4.457 × 10^–9 A/cm²) by 2 orders of magnitude than that of the Ti substrate, indicating enhanced corrosion protection in the SBF. PVDF/0.1CPF coating showed an antibacterial efficacy of 84.44% against Escherichia coli and 88.33% against Bacillus licheniformis after 24 h. The biocompatibility result showed that after 5 days of culturing, the PVDF/0.1CPF was pointedly higher than that of the pure PVDF and uncoated specimens. Additionally, after 7 days of culture, the quantity of cells on the PVDF/0.1CPF coating continued to increase significantly, whereas the bare specimens and pristine PVDF showed a lower rate of proliferation. The proposed biocompatible polymeric coatings hold synergic antibacterial and corrosion-resistant potential for biomedical applications.

There is growing interest in generating in vitro models of tissues and tissue-related diseases to mimic normal tissue organization and pathogenesis for different purposes. The retina is a highly complex multicellular tissue where the organization of the cellular components relative to each other is critical for retinal function. Many retinopathies arise due to the disruption of this order. In this study, we aimed to generate a coculture model of retina-derived cells, namely RPE and Müller cells, in multiplexed 3D hydrogels. Using methacrylated gelatin (GelMA)-based 3D hydrogels, we compared the behavior of RPE and Müller cells when they were cultured together. These patterned multiplex hydrogels containing cells were cultured for several days to reflect how cells would reorganize themselves in the presence of another cellular component derived from the same tissue. Here, we present a multicellular multiplex platform for the creation of cellular networks with cells of retinal tissue that can be easily adapted to create more complex tissue-like alternatives for large-scale tissue modeling and screening purposes. We also present an alternative method of coculture by generating spheroids from one of the components while keeping the other component free and motile in the hydrogel. The latter model predicts enhanced possibilities of cellular interactions by retarding the movement of one of the component cells.

Among the secondary target organs for metastatic breast cancer, brain metastasis is extremely aggressive in nature, resulting in lower survival rates. These metastatic cancer cells have the potential to enter a dormant state in the brain, allowing them to survive for extended time periods. The brain microenvironment plays a key role in controlling the dormant phenotype, yet how various components of this microenvironment influence dormancy is not well understood. In this work, we employed hyaluronic acid (HA)-based hydrogels as a mimetic of the brain tissue environment to study the role of biochemical cues, specifically, the impact of laminin and laminin-derived peptides IKVAV and YIGSR on the regulation of brain metastatic breast cancer cell dormancy versus proliferation. We applied varying protein/peptide concentrations and confirmed functionalization on HA hydrogel surfaces. We then seeded 10,000 cancer cells on the hydrogel surface and cultured them for 5 days. We found that in the presence of laminin or IKVAV, MDA-MB-231Br cells transitioned from a rounded to a spread morphology and exhibited enhanced proliferation as the laminin/IKVAV concentration increased. In contrast, in hydrogels functionalized with YIGSR, these cells maintained a rounded morphology, with no impact on proliferation with varying YIGSR concentrations. We confirmed the involvement of αVβ3 integrin in mediating tumor cell phenotype in hydrogels functionalized with laminin. By evaluating known markers of dormancy and proliferation, we found a direct correlation between the presence of laminin and IKVAV and increased phosphorylated extracellular signal-regulated kinase 1/2 (p-ERK) positivity, along with decreased phosphorylated p38 (p-p38) positivity, while in hydrogels functionalized with YIGSR, the levels of both p-ERK and p-p38 remained unaltered. Finally, we demonstrated that when cells were transferred from IKVAV-deficient to IKVAV-rich hydrogels, the hydrogel induced cellular dormancy was reversible. Collectively, our findings provide insights into how laminin and laminin-derived cues regulate brain metastatic breast cancer cell dormancy versus proliferation.

Hemoglobin shows different contrasts on magnetic resonance imaging (MRI) depending on the iron and oxygenation states of heme. Functional brain MRI utilizes the differences in the concentrations of oxyhemoglobin and deoxyhemoglobin in cerebral blood vessels; blood clots produce strong magnetic susceptibility effects. We hypothesized that methemoglobin (MetHb)-based nanoparticles can act as MRI contrast agents because MetHb levels in red blood cells affect relaxivity and are strictly regulated to <1% in the blood. Herein, we describe the synthesis of methemoglobin-encapsulated liposomes (Met-HbVs) as contrast agents for MRI. Met-HbV, with a size of approximately 200 nm, increased longitudinal relaxivity (r₁) by 2.44-fold compared with hemoglobin-encapsulated liposomes in vitro. In contrast, the transverse relaxation capacity (r₂) of Met-HbVs was similar to that of the hemoglobin-encapsulated liposomes. Owing to its relaxivity, Met-HbV enhanced the signal intensity on T1-weighted images and angiography, especially in the veins. Furthermore, deleterious biological responses were seldom observed after Met-HbV administration in mice with chronic renal failure. In conclusion, Met-HbV possesses potential as a vascular contrast agent in MRI for angiography, with advantages over gadolinium-based contrast agents in terms of safety for patients with renal failure. To the best of our knowledge, this is the first report demonstrating the potential of MetHb as a biomaterial for contrast agents in MRI.

Multidrug resistance (MDR) infectious wounds are a major concern due to drug resistance, leading to increased patient morbidity. Lichenysin (LCN), a lipopeptide and biosurfactant obtained from certain strains of Bacillus licheniformis, has demonstrated an excellent antimicrobial property. The present study focuses on the fabrication and comprehensive evaluation of LCN-incorporated poly(vinyl alcohol) (PVA)/polycaprolactone (PCL)-based nanofiber scaffolds using an electrospinning technique as a potential wound healing biomaterial for the treatment of MDR infectious wounds in diabetic rats. The LCN-loaded PVA–PCL nanofiber scaffolds were characterized for their physicochemical, antimicrobial, in vitro cell line on L-929, hemocompatibility, flow cytometry, in vivo infectious wound healing, and enzyme-linked immuno sorbent assay (ELISA). Morphological analysis via scanning electron microscopy (SEM) images confirmed smooth and porous nanofibers with diameters in the range 200–300 nm. Fourier transform infrared and X-ray diffraction (XRD) results demonstrated the structural integrity, chemical compatibility, and amorphous nature of developed scaffolds. The scaffolds loaded with LCN demonstrated excellent water retention, moderate biodegradability, and sustained release of LCN for up to 72 h. Mechanical characterization demonstrated a robust tensile strength conducive to wound healing applications. Antimicrobial activity against Pseudomonas aeruginosa (P. aeruginosa) and Staphylococcus aureus (S. aureus) showed substantial antibacterial and antibiofilm activity. In vitro cell line studies showed enhanced cell adhesion, proliferation, migration, and viability, signifying the cytocompatibility of these scaffolds. In vivo studies demonstrated exceptional infectious wound healing potential in diabetic rats. These findings indicate that LCN-enriched PVA–PCL scaffolds hold significant potential as a therapeutic strategy for the treatment of MDR infectious wounds in diabetic rats through a multifaceted approach.

In the realms of modern medicine and environmental monitoring, there is an escalating demand for bacterial detection technologies that are rapid, precise, and highly sensitive. Conventional methods, however, are often hindered by their time-intensive nature, procedural complexity, and reliance on specialized laboratory equipment. This study introduces an innovative approach utilizing bovine serum albumin (BSA) as the dielectric layer and lysozyme (LYZ) as the bacterial sensing layer in organic field-effect transistors (OFETs). The combination of BSA and LYZ enhances both biocompatibility and detection sensitivity, enabling precise differentiation between Gram-positive and Gram-negative bacteria. BSA not only stabilizes the electrical performance of the OFET but also offers biodegradability and water solubility, contributing to environmental sustainability. These biocompatible OFETs can accurately detect bacterial concentrations ranging from 10⁴ to 10⁸ CFU/mL, with real-time response capabilities via multispike measurements. This research represents a significant step forward in the development of advanced, portable biosensors for use in complex biological environments, advancing bacterial detection technology.

Engineering thick skin tissue substitutes resembling the physiochemical and mechanical properties of native tissue is a significant challenge. Melt electrowriting (MEW) is a powerful technique with the capability of fabricating highly ordered structures with fine fiber diameters, closely replicating the native extracellular matrix (ECM). In this study, we constructed melt electrowritten porous polycaprolactone (PCL) scaffolds with three different geometries by depositing fibers at 0–90 and 60–120° in a mesh structure and in a honeycomb-like orientation to assess the effects of the microstructure on the mechanical strength of the scaffold and cellular behavior. These scaffolds were subsequently infilled with gelatin hydrogel, encapsulating human skin dermal fibroblasts (HSFs) and human umbilical vein endothelial cells (HUVECs). Mechanical tensile tests revealed that the honeycomb microstructure of the hybrid PCL/gelatin scaffold exhibited greater elongation at failure, along with an acceptable elastic modulus suitable for skin tissue applications. All scaffolds provided a cytocompatible microenvironment that maintained over 90% cell viability and preserved typical cell morphology. HSFs were guided through the PCL fibers to the apical surface, while HUVECs were distributed within the gelatin hydrogel within the hybrid structure. Additionally, HSFs’ alignment was regulated by the scaffold geometry. Notably, the expression of CD31 in HUVECs─a key transmembrane protein for capillary formation─increased significantly over a 14 day incubation period. Among those, 0–90° mesh and honeycomb geometries showed the greatest effects on the upregulation of CD31. These findings demonstrate that the microstructural guidance of HSFs and their interaction with HUVECs in hybrid structures play a crucial role in promoting vascularization. In conclusion, the honeycomb MEW-gelatin hybrid scaffold demonstrates significant potential for effectively replicating both the mechanical and physicochemical properties essential for full-thickness skin tissue substitutes.

Wound healing is a complex and dynamic process of replacing missing cellular structures and tissue layers. Clinical practice includes the application of a sterile bandage to promote healing and to restrain infection, like the commercial nonbiodegradable meshes. However, while inert, nontoxic, and nonimmunogenic, they can cause calcification, fibrosis, and inflammation, potentially hindering the healing process in the long term. To address this challenge and enhance wound healing, we developed a totally biodegradable electrospun poly(d,l-lactide-co-ε-caprolactone) (PDLLCL) drug delivery system that incorporates two already FDA-approved antifibrotics, pirfenidone (PIRF) and triamcinolone acetonide (TA). The PDLLCL meshes, fabricated via electrospinning, exhibited homogeneity and complete degradation after 120 days, consistent with the wound healing process. In vitro, functional analysis on RAW 264.7 macrophages revealed no cytotoxicity and an immunomodulatory effect of PIRF and TA compared with the positive control (lipopolysaccharides, LPS) and the PDLLCL meshes alone. Lastly, subcutaneous in vivo assessment on a rabbit model, following the ISO 10993–6 standard, showed that our tailored made PDLLCL meshes were able to lower both irritation and fibrosis indexes from 2 weeks to 4 weeks of implantation, highlighting the beneficial effect of biodegradable polymers. However, we saw no significant positive effect on the incorporation of antifibrotics in vivo for irritation and fibrosis indexes. This underscores the potential of PDLLCL meshes as a possible alternative for wound healing, reducing the use of intermittent antifibrotic agents during the healing process.

Implant-associated infections pose significant challenges due to bacterial resistance to antibiotics. Recent research highlights the potential of immobilizing antimicrobial peptides (AMPs) onto implants as an alternative to conventional antibiotics for the prevention of bacterial infection. While various AMP immobilization methodologies have been investigated, they lack responsiveness to biological cues. This study proposes an enzyme-responsive antimicrobial coating for orthopedic devices using KR-12, an AMP derived from Cathelicidin LL-37, coupled with the Human Elastin-Like Polypeptide (HELP) as a biomimetic and stimuli-responsive linker, while mimicking the extracellular matrix (ECM). During implantation, these customized interfaces encounter the innate immune response triggering elastase release, which degrades HELP biopolymers, enabling the controlled release of KR-12. After coupling KR-12 with HELP to titanium surfaces, the antimicrobial activity against four pathogenic bacterial strains (Staphylococcus aureus, Staphylococcus epidermidis, Escherichia coli, and Pseudomonas aeruginosa) was assessed, revealing an inhibition ratio of bacterial adhesion and colonization exceeding 92% for all tested strains, compared with surfaces functionalized with KR-12 only. It is thought that the enhanced antimicrobial activity was due to the improved mobility of KR-12 when coupled with HELP. Furthermore, the prepared coatings boosted the adhesion and proliferation of human osteoblasts, confirming the cytocompatibility. These findings suggest the potential for smart coatings that combine the antimicrobial functions of AMPs with HELP’s biological properties for use in a variety of settings, including medical devices.

Aggressive solid tumors are associated with rapid growth, early hypoxia, a lack of targeted therapies, and a poor prognosis. The hypoxic niches within the rapidly growing solid tumors give rise to a stem-cell-like phenotype with higher metastasis and drug resistance. To overcome the drug resistance of these regions, we used hypoxia-responsive polymersomes with an encapsulated anticancer drug (doxorubicin, Dox) and a stemness modulator (all-trans retinoic acid, ATRA). Reductase enzymes overexpressed in hypoxia reduce the azobenzene linker of the polymers, disrupt the bilayer structure of the polymersomes, and release the encapsulated drugs. We used triple-negative breast cancer (TNBC) as a representative of aggressive and hypoxic solid tumors. We observed that ATRA synergistically enhanced the efficacy of Dox in killing cancer cells. A synergistic combination of the two drug-encapsulated polymersomes reduced the volumes of patient-derived TNBC spheroids by 90%. In contrast, Dox alone decreased the spheroid volumes by 70% and encapsulated ATRA by 19%. Mechanistic studies revealed that ATRA inhibited efflux pumps, leading to a higher concentration of doxorubicin within TNBC cells. In addition, the combination of encapsulated Dox and ATRA significantly decreased stemness expression of the TNBC cells in hypoxia compared to that of Dox alone.

Carbon nanomaterials (CNM), including carbon nanotubes (CNT) and graphene nanoplatelets (GNP), are expected to have diverse industrial applications due to their unique physical properties. However, concerns have been raised regarding their toxicity in humans. In this context, risk assessment must include an understanding of the molecular mechanisms underlying human recognition of CNM. We have recently identified human sialic acid-binding immunoglobulin-like lectin (Siglec)-14 as a CNT-recognizing receptor. Since no rodent orthologs for Siglec-14 exist, previous rodent toxicological studies may underestimate CNM toxicity in humans. Therefore, in this study, we investigate Siglec-14 responses to various CNM. Siglec-14 recognizes various types of CNM via its extracellular aromatic cluster with a similar affinity, regardless of size and shape. Ultrathin single-walled CNT (SWCNT) and spherical carbon black nanoparticles (CBNP) activated macrophage Siglec-14 signaling, leading to IL-8 production. Notably, GNP as well as long needle-like MWCNT not only activate this inflammatory signal but also cause phagosomal damage, leading to the release of IL-1β, the most prominent pro-inflammatory cytokine. In mice transduced with Siglec-14, intratracheal injection of GNP or long needle-like MWCNT caused lung inflammation, whereas injection of SWCNT or CBNP did not. Taken together, these results suggest that CNM-induced inflammation requires two processes: macrophage receptor ligation and phagosomal damage. This indicates that CNM may be safe unless they cause damage to the macrophage phagosome.

Autophagy plays a complex role in cancer progression, serving as both a tumor suppressor and a promoter, depending on the context. In triple-negative breast cancer (TNBC), a particularly aggressive subtype with limited therapeutic options, autophagy inhibition has emerged as a promising strategy to enhance the efficacy of chemotherapy. This study investigates the synergistic effects of autophagy suppression using LC3 siRNA-loaded “smart” nanoparticles (LC3siRNA-NPs) in combination with doxorubicin (DOX) to overcome chemoresistance in TNBC. We engineered a well-defined copolymer, poly[hexyl methacrylate-co-2-(dimethylamino) ethyl methacrylate-co-trimethylaminoethyl methacrylate iodide], and a PEG heteroarm beta-cyclodextrin (βCD) core star copolymer that delivers LC3 siRNA, effectively silencing the autophagy-related gene LC3. In vitro, the coadministration of LC3siRNA-NPs and DOX significantly inhibited TNBC cell proliferation, migration, and colony formation, while inducing apoptosis more effectively than either treatment alone. Mechanistically, this combination downregulated key oncogenic markers such as PARP, cyclin D1, and Src, enhancing the therapeutic outcome. In vivo, treatment with LC3siRNA-NPs and DOX in a TNBC xenograft model resulted in superior tumor growth suppression compared to that with monotherapy alone. Our findings highlight the potential of autophagy-targeting nanocarriers to improve chemotherapy outcomes and provide an effective approach to TNBC treatment by enhancing chemotherapeutic sensitivity and reducing tumor resistance.

Nanocarrier systems with multifunctional capabilities hold great potential for targeted cancer therapy, particularly for breast cancer treatment. Metal–organic frameworks (MOFs) are notable for their high porosity and, in some cases, biocompatibility, with ZIF-8 being particularly advantageous due to its pH-sensitive degradability, enabling selective drug release in tumor environments. Additionally, lanthanide-doped upconversion nanoparticles (UCNPs) offer unique optical properties that enhance both imaging and therapeutic applications. In this study, NaYF₄/Yb³⁺Er³⁺ UCNPs were synthesized via a hydrothermal method, subsequently coated with poly(acrylic acid) (PAA) and encapsulated within a ZIF-8 shell, forming of UCNP@ZIF-8 core–shell nanocomposites. This system was designed to leverage stimulation by a 980 nm laser and acidic pH to facilitate drug release. When exposed to this specific laser wavelength, the nanocomposites demonstrated significantly enhanced drug release, achieving up to 90% release of the incorporated antitumor drug, doxorubicin (DOX), in acidic environments. In vitro studies indicated selective cytotoxicity, with MCF-7 tumor cell viability decreasing from 85.7% to 20% following laser activation, while showing minimal toxicity toward healthy cells. These findings underscore the potential of the UCNP@ZIF-8 nanocarrier system as a pH and laser-responsive platform for improved cancer therapy, enabling precise control over drug delivery while minimizing side effects on surrounding healthy tissues.

This study introduces a comprehensive approach to enhancing SiN_x nanofilters for exosome isolation from bovine milk using the electrophoretic oscillation-assisted tangent-flow ultrafiltration (EPOTF) process. Reinforcing the nanofilter with electro-spun poly(vinylidene fluoride) (PVDF) fibers significantly improved durability under high-pressure conditions, withstanding nearly 2.8 times greater pressures than nonreinforced nanofilters. The PVDF-fiber-coated nanofilters achieved a flow rate of over 70 mL min^–1, compared to just 25 mL min^–1 for nonreinforced nanofilters. A filter housing system with copper electrodes isolated from the solution flow path further enhanced the electrical stability of the entire system, widening the EPO voltage range while reducing the risk of corrosion and contamination. The PVDF-fiber-coated nanofilter with the electrode in a separated housing efficiently prevented clogging and bioparticle agglomeration, maintaining constant filtration performance across various voltages and duty cycles. Biochemical analyses confirmed the high concentration and structural integrity of exosomes isolated at high flow rates. Long-term tests verified the superior performance of PVDF-coated filters, successfully filtering 3400 mL of milk over 24 h. These results demonstrate the potential of these advances for highly efficient exosome isolation while maintaining the integrity and shape of exosomes, offering promise for the future of exosome isolation research.

In this study, we developed a biosensor that makes use of recombinase polymerase amplification (RPA) along with a CRISPR/Cas12a system integrated with silica nanobeads and a magnetic nanoparticle nanohybrid complex that displayed peroxidase-mimicking properties. This nanohybrid nanozyme (NZ) integration with the CRISPR/Cas system allowed dual-mode fluorometric and colorimetric responses . The nanohybrid NZ was a conjugated ssDNA quencher probe sequence with inherent fluorometric properties. In the presence of target RPA amplicons, the CRISPR/Cas12a system gets activated, cleaving the probe sequence attached to the NZ complex and leading to fluorescence signal generation. Post-CRISPR/Cas12a assay, the presence of the NZ in the reaction mixture, after being cleaved away from the probe sequence, gave a colourimetric response directly proportional to the target DNA concentration, as the ssDNA probe sequence no longer hindered its catalytic activity. Therefore, the dual-mode detection using the CRISPR/Cas12a-based fluorometric response and NZ-based colorimetric detection conferred high sensitivity and selectivity toward Campylobacter detection. The developed sensor could detect the pathogenic DNA at concentrations as low as 0.98 pg/μL and 0.96 pg/μL via fluorescence and absorbance spectroscopy, respectively. In addition, our method was also tested in raw food analysis and showed good recovery.

In quest of a new working design for a photostable lipid-droplets (LDs) bioimaging probe, we herein unveil and demonstrate a twisted donor(naphthalene)−π–acceptor(dicyano) architecture linked with oxo/thioether functionality, where the probes’ emission, hydrophobicity, cytotoxicity, and cell permeability are altered by replacing the present chalcogen/s. In this class of molecules, an “oxanthrene”-based compound, “OXNCN”, was realized as the noncytotoxic and cell-permeable probe, displaying intense fluorescence in a nonpolar solvent, aggregates, and viscous medium. Time-dependent density functional theory (TD-DFT) investigations revealed that OXNCN holds a favorable extent of excited-state planarity to bring out considerable emission only in a nonpolar solvent, resulting in polarity-dependent emission. Outcomes of the concentration- and time-dependent colocalization investigations, cholesterol depletion/repletion studies, and oleic acid treatment-based experiments validated its LD specificity. Strong twisted intramolecular charge transfer (TICT) culminated in weak emission in the polar medium, which helped the probe reduce the cytoplasmic signal. Moreover, the results of time-dependent kinetic acquisitional photophysical studies, fluorescence recovery after photobleaching (FRAP), and intracellular emission investigations testified to the probe’s photostability. Assiduous analysis and quantification of confocal laser scanning microscopy (CLSM) images by two-way analysis of variance (ANOVA), followed by Sidak’s multiple comparison statistics, could provide insights into the probe’s better performance in robust cancer cells (FaDu) than in normal ones (HEK-293). A precise discrimination between oral and normal cancer cells could be established by quantifying the deposited lipid droplets from the CLSM-captured cellular images and applying Student’s t test with the quantified values.

Excess accumulation of misfolded and mutated human lysozyme (HuL) is the pathological hallmark of non-neuropathic systemic amyloidosis. These deposits are rich in cross β-sheet conformers and often exist as polymorphic fibrillar structures, which makes it a tricky and challenging task to design therapeutic interventions toward HuL-linked amyloidopathy. Here we aimed to design an effective antiamyloid metal nanoparticle formulation to target the exposed hydrophobic and aggregation-prone stretches in HuL. Initially, we synthesized and characterized piperine-coated gold nanoparticles (AuNPs^Pip). ThT-probed aggregation studies of HuL in the presence and absence of AuNPs^Pip revealed an inhibition of lysozyme aggregation. This inhibition effect was confirmed through dynamic light scattering (DLS) and fluorescence microscopy analyses. We further investigated whether AuNPs^Pip could bind to preformed fibrils and prevent the secondary nucleation process, which is a crucial step in amyloidogenesis. Our results showed that AuNPs^Pip not only prevented seed-induced aggregation but also disassembled preformed amyloid aggregates, which was not observed with AuNPs or piperine. Experimental and computational studies suggest that the retention of the lysozyme native structure and the ability of AuNPs^Pip to interact with the aggregation-prone residues are key factors in the inhibition mechanism. The findings of this work may aid in developing nanoparticle-based formulations to prevent pathologies linked to lysozyme aggregation.

AISI 420 martensitic stainless steel is used for the manufacture of surgical and dental instruments, among others, whose surfaces can be colonized by bacteria and/or viruses that negatively affect the health of patients. The use of binary and ternary nitride coatings doped with different metallic nanoparticles has contributed to reducing the problems of infection with bacteria. However, there are few reports and studies on the biocidal and virucidal effect of high-entropy nitride coatings doped with silver nanoparticles, which could be an important alternative for antibacterial applications, also considering other advantages such as their excellent mechanical and tribological properties. In this work, a high-entropy nitride of (TiTaZrNbN)Agx doped with silver particles (Ag) was synthesized on AISI 420 stainless steel substrates via the magnetron sputtering technique. An attempt was made to elucidate the relationship between the microstructure and surface properties of the coatings with their potential activity against the selected bacteria and viruses. The Ag content in the coatings varied between 15.4 and 26.8 atom % by increasing the power supplied to the silver target between 50 and 110 W. The bactericidal effect of the synthesized nitride compound was studied via inhibition and adhesion tests against the bacteria Pseudomonas aeruginosa and Staphylococcus aureus. Moreover, the SARS-CoV-2 virus was selected to determine its virucidal effect. The deposited coatings exhibited columnar growth, and both the metal nitride matrix and the silver particles presented a NaCl-type cubic structure with preferential growth in the (111) and (200) planes. All of the coatings had a columnar structure whose width, surface roughness, and grain size increased with increasing silver content. Furthermore, the coatings present a hydrophobic behavior (increasing contact angle with increasing silver content) and decreasing surface energy. All of the coated steel samples strongly inhibited P. aeruginosa bacteria, and only sample RN-50W, with the lowest silver content, presented low adhesion of this bacteria. None of the coatings inhibited the S. aureus bacteria, and all of the coatings highly colonized the S. aureus bacteria in the adhesion test. The coatings deposited with powers of 50 and 90 W supplied to the silver target presented an average virucidal potential of 50% against the SARS-CoV-2 virus.

Accurate temperature sensing at the nanoscale within biological systems is crucial for understanding various cellular processes, such as gene expression, metabolism, and enzymatic reactions. Current temperature-sensing techniques either lack the temperature resolution and sensitivity necessary for intracellular applications or require invasive procedures that can disrupt cellular activities. In this study, we present Nile Red (NR)-loaded hybrid (span 60-L64) niosomes and Nile Red-loaded L64 niosomes as highly sensitive fluorescent nanothermometers. These niosomes are synthesized via the thin-layer evaporation method, forming thermoresponsive vesicles, and they demonstrate reversible phase transition behavior with temperature. When loaded with polarity-sensitive Nile Red, vesicles exhibit a strong temperature-dependent fluorescence response (change in intensity, emission maximum, and lifetime), suitable for noncontact temperature sensing in the biologically important temperature range of 25 to 50 °C. While NR-hybrid niosomes exhibit a high relative sensitivity of 19% °C^–1 at 42 °C, NR-L64 niosomes achieved extraordinary relative sensitivity of 36% °C^–1 at 40 °C. Using NR-L64 niosomes, the temperature resolution is found to be 0.0004 °C at 40 °C. The nanothermometers displayed excellent photostability, thermal reversibility, and resistance to variations in ion concentration and pH. Temperature-dependent confocal microscopy using FaDu cells confirmed the biocompatibility and effectiveness of the designed nanothermometers for precise intracellular temperature sensing. The results demonstrate the significant potential of Nile Red-loaded niosomes for temperature monitoring using live cell imaging in biological media.

Nanoparticle technology, particularly gold nanoparticles (AuNPs), is being developed for a wide range of applications, including as a delivery system of peptides or nucleic acids (NA). Their use in precision medicine requires detailed engineering of NP functionalization to optimize their function and minimize off-target toxicity. Two main routes can be found in the literature for the attachment of NA strands to AuNPs: covalent binding via a thiol group or passive adsorption onto a specially adapted coating previously applied to the metallic core. In this latter case, the coating is often a positively charged polymer, as polyethylenimine, which due to its high positive charge can induce cytotoxicity. Here, we investigated an innovative strategy based on the initial coating of the particles using calix[4]arene macrocycles bearing polyethylene glycol chains as an interesting alternative to polyethylenimine for NA adsorption. Because any molecular modification of AuNPs may affect the cytotoxicity and cellular uptake, we compared the behavior of these AuNPs to that of particles obtained via a classical thiol covalent attachment in MCF-7 and GC-1 spg cell lines. We showed a high biocompatibility of both AuNPs-NA internalized in vitro. The difference in subcellular localization of both AuNPs-NA in MCF-7 cells compared to GC-1 spg cells suggests that their subcellular target is cell- and coating-dependent. This finding provides valuable insights for developing alternative NA delivery systems with a high degree of tunability.

Astaxanthin is an antioxidant with extremely high antioxidant activity. However, the stability and solubility of free astaxanthin are poor. Therefore, we prepared astaxanthin-betaine (ASTA-Bet) ionic liquid liposomes through a combination of theoretical calculations and experimental research and studied their physicochemical properties and biological effects. This liposome has good stability and skin permeability. The cumulative permeability of the ASTA-Bet ionic liquid liposome is 22.95 times that of free astaxanthin and 2.41 times that of the ASTA-Bet ionic liquid. The particle size of astaxanthin liposomes was 117.2 nm, and the particle size did not change significantly after 28 days of storage, indicating good stability. Compared with free astaxanthin, the ASTA-Bet ionic liquid liposome has good antioxidant activity and can exert antioxidant and anti-inflammatory effects by regulating the TGF-β1/smad2/smad3 pathway damaged by ultraviolet radiation, which may contribute to the resistance to ultraviolet radiation damage. Therefore, it can be used as a raw material to develop cosmetics with antiaging and anti-inflammatory functions.

To combat the emerging threat of antimicrobial resistance (AMR), in this study, two amphiphilic nucleopeptides (NPs) were synthesized by conjugating the nucleobase thymine with peptide amphiphiles. These compounds were fully characterized using various analytical techniques. Notably, both nucleopeptides formed hydrogels in milli-Q water at neutral pH (pH 6.9). X-ray diffraction further confirmed antiparallel β-sheet-like structures, along with aromatic π–π stacking and hydrogen-bonding (H-bonding) interactions between the thymine moieties in the gel phase. Field emission gun transmission electron microscopy revealed a nanofibrillar network structure in these self-assembled peptides. A significant feature of these peptide supramolecular self-assemblies is their potent antimicrobial activity against both types of bacteria, such as Gram-positive and Gram-negative standard American Type Culture Collection (ATCC) bacteria, including Bacillus subtilis, Escherichia coli, and multidrug-resistant clinically isolated ATCC strains such as methicillin-resistant Staphylococcus aureus (MRSA), Klebsiella pneumoniae, and Pseudomonas aeruginosa. Among these, both peptides demonstrated remarkable inhibition of MRSA (MIC: 15.92–16.86 μM) and K. pneumoniae (MIC: 8.8–50 μM), highlighting their potential as antimicrobial agents against deadly multidrug-resistant (MDR) bacteria. Additionally, these peptide assemblies were found to be highly biocompatible, as demonstrated by MTT assays on HEK-293 cells, showing IC₅₀ values in the range of 0.5–1.1 mM. In an in vitro wound healing assay using HeLa cells, fluorescence microscopy confirmed that treatment with these nucleopeptides did not disrupt the cell or mitochondrial membranes in HEK-293 cells. This work presents two nucleopeptides with broad-spectrum antimicrobial efficacy against MDR strains and demonstrates high biocompatibility, supporting their potential use as antimicrobial agents.

An effective and rapid hemostatic material with flexible properties for clinical wound dressings is still an unmet need. Herein, a porous sodium carboxymethyl starch (CMS–Na-P) hemostatic microsphere was successfully fabricated through polysaccharide fluffy aggregate (PSFA) technology with a facile and low-cost process. CMS–Na-P exhibited rapid water absorption capabilities alongside favorable cytocompatibility and hemocompatibility. Additionally, CMS–Na-P could absorb red blood cells (RBCs), adhere to and activate platelets, and shorten clotting time in vitro. More importantly, its good in vivo hemostatic ability was further demonstrated against hemorrhage in rat liver and tail, pig superficial skin, superficial body vein, superficial abdominal vein, and femoral artery. Meanwhile, in a rat full-thickness skin defect model, CMS–Na-P could enhance wound healing through accelerated epidermal regeneration and collagen deposition. These properties make CMS–Na-P a promising candidate for treating bleeding and full-thickness wounds.

Photodynamic therapy (PDT) is a clinically approved noninvasive treatment for cancer that employs a photosensitizer (PS) to generate cytotoxic reactive singlet oxygen (ROS) species that precisely destroy cancer cells at the targeted tumor sites. There is growing interest in the development of innovative photosensitizing agents and advanced delivery methods, offering superior phototherapeutic performance. The delivery of PS is a challenging task in PDT in regard to the high hydrophobicity of the PS molecule. To address this challenge, the incorporation of heavy-atom-free PS (HAF-PS) in effective drug delivery carriers is promising for PDT improvement. Herein, we propose a strategy to encapsulate the HAF-PS from the perylenediimide (PDI) family in the oily core of lipid nanocapsules (LNCs). The resulting HAF-PS-loaded LNCs formulations have the advantage to efficiently generate singlet oxygen (¹O₂) in a biorelevant environment. The LNCs formulations loaded with O-PDI (O-PDI@LNC) and 1S-PDI (1S-PDI@LNC) were obtained by a solvent-free phase-inversion temperature (PIT) method. Our study demonstrates that optimized LNCs formulation loaded with 1S-PDI acting as PS is a highly efficient approach to deliver phototherapeutic agents for PDT. Overall, it has been shown that illumination of 1S-PDI leads to dramatic ¹O₂ production with an impressive quantum yield (φSOQY = 0.94) which was tested with 1,3-diphenylisobenzofuran (DPBF) as a specific trap. Moreover, the ¹O₂ generation was calculated in a phosphate buffer solution (φSOQY = 0.52) for loaded nanocarrier 1S-PDI@LNC. In vitro cytotoxicity studies demonstrated a low dark toxicity of 1S-PDI@LNC while illumination significantly enhanced its photocytotoxicity in cells. Furthermore, the cellular internalization of LNCs was demonstrated in U-87 MG cells using O-PDI@LNC as a model, exploiting the excellent fluorescence properties of O-PDI. This study has significant potential for advancing the development of HAF-PS-loaded LNCs for minimally invasive PDT.

The favorable success rate in cancer treatment predominantly depends on precise diagnosis with target-specific drug delivery, which can regulate the patient survival outcome rate. Moreover, proper tracking of the system’s pH is very much crucial as most of the therapeutic’s action and release rate depend on it. Therefore, this work has been intended to fabricate a folic acid-derived carbon dot (FACD) decorated with chitosan (Cs) in order to form nanospheres (FACD-Cs-Ns) for anticancer doxorubicin hydrochloride (Dox.HCl) drug delivery through imaging in cancer therapeutic treatment. The engineered FACD-Cs-Ns demonstrated a spherical shape with an extensive surface area, rich in carboxyl and hydroxyl groups that play a key role in its pH-responsive characteristics through protonation and deprotonation interactions. Thanks to their impressive fluorescence traits and excellent stability, FACD-Cs-Ns are particularly well suited for imaging-guided cancer therapy. Their remarkable cytocompatibility with normal cells and significant toxicity toward cancer cells, along with pH-responsive properties, render them as ideal candidates for targeted drug delivery to cancer cells. The G2/M and S phases’ arrest in the cell cycle analysis study once more validated excellent in vitro experimental conditions. The impressive selectivity and cytotoxicity of Dox-loaded FACD-Cs-Ns toward cancer cells can be attributed to enhanced cellular uptake via folate-receptor-mediated endocytosis, which is overexpressed in these cells. These findings elucidate that the FACD-Cs-Ns nanoprobe is an excellent material for pH-responsive anticancer drug delivery and image-guided cancer therapy.

The structural and optical properties, as well as the electrical and biological characteristics of a porous platinum (Pt) structure for neurostimulation applications, are investigated. Critical factors such as biocompatibility, electrical performance, and structural and optical differences, which can adversely affect the functionality of implantable devices, are systematically analyzed and compared with general electrodes. By employing an integration of three-dimensional simulations and implantation experiments, we demonstrate that the remarkably extensive surface area, low reflectance, and outstanding peak current values inherent in porous Pt facilitate effective stimulation while simultaneously ensuring a high degree of biological safety. Our findings suggest that these beneficial characteristics collectively position porous Pt as a notably promising candidate for implantable electrodes in biomedical devices.

Glioblastoma (GBM) is an aggressive and fatal tumor. The infiltrative spread of GBM cells hinders gross total resection. The residual GBM cells are significantly associated with survival and recurrence. Therefore, a theranostic method that can enhance the contrast between residual GBM and normal astrocyte (AS) cells and selectively eradicate GBM cells is highly desired. In this report, GBM and normal astrocyte cells are both cultured in the same microplate well to imitate a coexistence environment and treated with Raman tags functionalized by anti-EGFR. Compared to AS cells, GBM cells show 25% higher Raman emission, and their cell death rate increases by a factor of 2. These results demonstrate the potential for selective eradication of the residual GBM cells guided by robust Raman signals after the primary GBM surgery.

Zearalenone (ZEN) is one of the most prevalent mycotoxins in the world, with estrogenic toxicity leading to significant annual economic losses and environmental pollution. RmZHD, a novel ZEN hydrolase, surpasses the efficiency of its predecessors but faces challenges in large-scale industrial application. In this work, an engineered Escherichia coli that can degrade zearalenone is constructed based on synthetic biology and surface display methods. It can degrade 94% of zearalenone at 30 °C in 1 h (the final concentration was 1.898 μg/mL) and effectively degrade ZEN-derived toxins, including zearalanone, β-zearalanol, α-zearalenol, and β-zearalenol. This engineered E. coli requires no additional manipulation for the surface display of RmZHD and is cost-effective to produce. Moreover, it exhibits the capability to degrade ZEN in maize feed while concurrently mitigating inflammation in animal reproductive and digestive organs. In summary, the engineered E. coli with surface-displayed RmZHD presents a novel approach for environmentally sustainable and industrial-scale treatment of ZEN.

Through the PFOEP-SO3(−) + multidrug molecules constructed nanoparticle (NP) experiments and validated by molecular simulation docking experiments, we propose a molecular interaction principle for inducing aggregation-induced locally excited emission (AILE) luminescence from fluorenone (FO)-based conjugated polymers (CPs). Based on this molecular interaction mechanism, we constructed a NP built by π–π stacking. The NPs demonstrate facile synthesis, robust stability, and high drug-loading efficiency, enabling tumor-specific drug release in acidic lysosomal environments (pH 3.8–4.7) to minimize off-target toxicity. Concurrently, the PFOEPA NPs exhibit pH-dependent fluorescence enhancement: drug incorporation induces structural reorganization into a “sandwich” configuration, amplifying fluorescence with a blue shift under neutral/alkaline conditions, while acidic-triggered protonation collapse disrupts NPs. Moreover, it can be used as an indicator for monitoring drug release, as it is accompanied by changes in fluorescence during the drug release process. This NP possesses multiple functions and is expected to serve as an effective pH-responsive drug delivery system.

Micropatterned surface substrates containing topographic cues offer the possibility of programming tissue organization as a cell template by guiding cell alignment, adhesion, and function. In this study, we developed and used a force stamp method to grow aligned micropatterns with tunable chemical properties and elasticity on the surface of hydrogels based on a force-triggered polymerization mechanism of double-network hydrogels to elucidate the underlying mechanisms by which cells sense and respond to their mechanical and chemical microenvironments. In this work, we describe the impact of aligned micropatterns on the combined effects of microstructural chemistry and mechanics on the selective adhesion, directed migration, and differentiation of myoblasts. Our investigations revealed that topographically engineered substrates with hydrophobic and elevated surface roughness significantly enhanced myoblast adhesion kinetics. Concurrently, spatially ordered architectures facilitated cytoskeletal reorganization in myocytes, establishing biomechanically favorable niches for syncytial myotube development through extracellular matrix (ECM) physical guidance. Reverse transcription PCR analysis and immunofluorescence revealed that the expression of differentiation-specific genes, myosin heavy chain, and myogenic regulatory factors Myf5 and MyoD was upregulated in muscle cells on the aligned patterned scaffolds. These results suggest that the aligned micropatterns can promote muscle cell differentiation, making them potential scaffolds for enhancing skeletal differentiation.

The emergence of immunotherapy as a revolutionary therapeutic modality has fostered confidence and underscored its potent efficacy in tumor therapy. However, enhancing the therapeutic efficacy of immunotherapy by precise and judicious administration poses a significant challenge. In this context, we have developed a disulfide-bearing transdermal nanovaccine by integrating a thiol-reactive agent lipoic acid (LA) into a metal-coordinated cyclic dinucleotide nanoassembly, designated as LA-Mn-cGAMP (LMC) nanovaccines. Upon topical application to the skin with melanoma, the dithiolane moiety of LA enables thiol–disulfide dynamic exchange in the skin, hence facilitating penetration into both the skin and subcutaneous tumor tissues via the thiol-mediated uptake (TMU) mechanism. Our findings demonstrate that transdermal administration of LMC significantly enhances STING activation, mitigates the immunosuppressive tumor microenvironment (TME), and retards melanoma progression. Moreover, the remodeled TME amplifies the efficacy of immune checkpoint inhibitors. This advancement offers an administration strategy for existing STING agonist therapy, potentially improving the biosafety of immunotherapy.

Polymer nanobiocomposites (PNCs) prepared with graphitic carbon nitride (GCN) nanosheets in polybutylene adipate terephthalate (PBAT)/polylactic acid (PLA) bioblends were processed using a three-step processing technique that involved: (1) a solution-based GCN exfoliation step; (2) a masterbatching step of GCN in PBAT by solution processing; and (3) a melt-compounding step where the masterbatch was mixed with pristine PLA to delaminate the 2D GCN layers by extrusion high-shear mixing and to deposit them onto the biphasic PLA/PBAT morphology. Due to the partial exfoliation of GCN, this process led to a concurrent presence of three distinct morphologies within the PNCs’ microstructure: (1) Type 1, characterized by an unaltered interface and PLA matrix, with minimal GCN deposition within the PBAT phase; (2) Type 2, distinguished by a diffused and stiff interface with GCN distribution in both the dispersed (PBAT) and matrix (PLA) phases; and (3) Type 3, featuring unmodified interfaces and GCN localization across both PLA and PBAT phases with a stair-like morphological texture. Such a morphological combination generates distinct crack propagation micromechanics, thereby influencing the variability of the plastic deformational behavior of their PNCs. Particularly, the Type 1 morphology enables GCN to act as a secondary stress-dissipating agent, whereas the PBAT domains serve as the primary stress-absorbing sites, contributing to enhanced crack propagation energy requirements. Contrarily, Type 3 (slightly) and Type 2 (predominantly) morphologies invert GCN’s role from stress dissipation to stress concentration due to its localization within the PLA matrix. Differential scanning calorimetry revealed a crystallinity increase in the PNCs until 0.1 wt % GCN, followed by a decline, likely due to agglomeration at higher contents. Thermogravimetric analysis showed that GCN addition improved the thermostability of the bioblends, attributed to the GCN’s nanophysical and pyrolytic barrier effect. Moreover, using both direct and indirect methods, GCN did not impair the biocompatibility of the bioblends as confirmed via cytocompatibility assays.

STAT3 is an important protein responsible for cellular proliferation, motility, and immune tolerance and is hyperactive in colorectal cancer, instigating metastasis, cellular proliferation, migration, as well as inhibition. It helps in proliferation of myeloid-derived suppressor cells (MDSCs), which within the tumor microenvironment (TME) suppress T cells to encourage tumor growth, metastasis, and resistance to immunotherapy, besides playing dynamic role in regulating macrophages within the tumor. Thus, MDSC is a potential target to augment immune surveillance within the TME. Herein, we report targeting both colorectal cancer and MDSCs using a glucocorticoid receptor (GR)-targeted nanoliposomal formulation carrying GR-ligand, dexamethasone (Dex), and a STAT3 inhibitor, niclosamide (N). Our main objective was to selectively inhibit STAT3, the key immunomodulatory factor in most TME-associated cells including MDSCs, and also repurpose the use of this antihelminthic, low-cost drug N for cancer treatment. The resultant formulation D1XN exhibited better tumor regression and survivability compared to GR nontargeted formulation. Further, bone marrow cell-derived MDSCs were engineered by D1XN treatment ex vivo and were inoculated back to tumor-bearing mice. Significant tumor growth inhibition with enhanced antiproliferative immune cell signatures, such as T cell infiltration, decrease in T_reg cells, and increased M1/M2 macrophage ratio within the TME were observed. This reveals the effectiveness of engineered MDSCs to modulate tumor surveillance besides reversing the aggressiveness of the tumor. Therefore, D1XN and D1XN-mediated engineered MDSCs alone or in combination can be considered as potent selective chemo-immunotherapeutic nanoliposomal agent(s) against colorectal cancer.

We developed two deep-red cyanine chromophores, probes A and B, for selective mitochondrial NAD(P)H detection in live cells. Probe A features a 1,2,3,3-tetramethyl-3H-indolium core, while probe B incorporates a 1,1,2,3-tetramethyl-1H-benzo[e]indol-3-ium moiety, both linked to quinolinium via a vinyl bond to enable fluorescence modulation upon NAD(P)H reduction of probes A and B. To explore the role of electron-withdrawing groups in probe sensitivity, we synthesized three additional cyanine dyes (probes C, D, and E) via condensation of 6-quinolinecarboxaldehyde with 2,3-dimethyl-1,3-benzothiazolium acceptor and malononitrile derivatives, followed by methylation. Under NAD(P)H-deficient conditions, probe A showed absorption at 382 nm with weak fluorescence at 636 nm, while probe B absorbed at 443 nm with weak fluorescence at 618 nm. Upon NAD(P)H reduction, probe A exhibited red-shifted absorption at 520 nm with enhanced emission at 589 nm, and probe B at 550 nm with strong emission at 610 nm. Probe C showed absorption at 524 nm with enhanced emission at 586 nm, while probes D and E exhibited no detectable NAD(P)H response, highlighting the critical role of quinolinium acceptors. Probe B demonstrated superior sensitivity, successfully tracking NAD(P)H fluctuations in HeLa cells under glycolysis stimulation (glucose, lactate, pyruvate) and treatments with LPS and methotrexate. It also visualized NAD(P)H in Drosophila larvae, revealing increased levels after drug treatments. Notably, probe B distinguished between healthy and diseased human kidney tissues, detecting significantly elevated NADH levels in autosomal dominant polycystic kidney disease (ADPKD) samples, emphasizing its diagnostic potential. This study introduces probe B as a versatile and reliable NAD(P)H sensor for metabolic research and disease diagnostics, offering valuable insights into redox processes in live cells, organisms, and clinical samples.

Combination chemotherapy is a promising strategy for cancer treatment, enhancing antitumor efficacy while minimizing drug resistance and mitigating the risk of single-drug overdose toxicity. Polymeric drug delivery carriers for combination chemotherapy have been developed; however, the synthetic process of amphiphilic polymers is time-consuming and laborious. The polymer entanglement-based drug encapsulation has been limited in achieving a high multidrug encapsulation efficiency because of the intrinsic preference for encapsulation of drugs upon their polarity. Herein, inspired by dynamic bonding and supramolecular assembly of metal-phenolic coordinate bonds at the oil/water interface, nanoemulsions were fabricated via a dropwise emulsion process. The emulsion interface was formulated by the coordinate bonds and created a colloidally stable emulsion with 50–100 nm in diameter for 3 weeks. These nanoemulsions enabled the coencapsulation of anticancer drugs, hydrophilic gemcitabine, and hydrophobic paclitaxel. Moreover, the treatment of dual-drug-encapsulated nanoemulsions reduced cellular viability (57.0 ± 0.0%) compared to that of gemcitabine only encapsulated (84.0 ± 9.9%) and paclitaxel only encapsulated (83.4 ± 7.2%) nanoemulsion treatment, demonstrating the potential of multidrug delivery carriers for synergistic combination therapy.

Ultrasound and microbubble-mediated gene delivery is emerging as a powerful nonviral gene delivery approach due to its ability to target various tissues. Since microbubble cavitation plays a crucial role in gene delivery, factors affecting cavitation, such as microbubble composition, size, ultrasound pressure, frequency, and pulse interval, can directly affect the efficiency of gene delivery. The effect of ultrasound parameters on gene delivery efficiency has been systematically investigated in numerous studies. However, relatively few studies have investigated the influence of different microbubble compositions on gene delivery. In this paper, we report that microbubbles made with the same lipids but different poly(ethylene glycol) (PEG) derivatives lead to significantly different gene delivery efficiencies in vitro. Moreover, we show that the type of PEG derivative used in microbubble formulations greatly influences the acoustic response of microbubbles (i.e., resonance frequency and frequency-dependent attenuation coefficient), thus explaining the differences in gene delivery efficiencies. Our results highlight that changing a single component in the microbubble formulation, i.e., the type of PEG derivative, can improve gene delivery efficiency by 3-fold. This comparative study of microbubbles made with different PEG derivatives may help researchers in designing microbubble formulations for optimal gene delivery.

Bone regeneration is a process that aims to restore the structure and function of damaged bone tissues. Modern approaches for bone regeneration involve a combination of strategies, including tissue engineering and biomaterials, to promote healing. In this study, electrospun nanofibers were developed by using biosynthesized chitosan (CS)- and graphene oxide (GO)-loaded polyacrylonitrile (PAN) nanofibers. These scaffolds demonstrated stable mechanical support and capability to promote rapid bone defect repair. The physicochemical properties of the prepared nanoparticles and nanofibers were characterized using XRD and XPS analysis. The nanofiber morphology and structure of the CS/GO composite were analyzed through SEM and TEM. In vitro studies and ALP activity demonstrated the membranes capability to promote new bone formation and support healing, and Alizarin red staining highlighted the membrane’s ability to enhance cell–cell interactions and increase calcium deposition, crucial for tissue regeneration. Cytotoxicity analysis revealed that 97.66 ± 1.5% of MG-63 cells remained viable on the surface of the prepared nanofiber, as assessed by the MTT assay. At the molecular level, real-time RT-PCR was used to examine the mRNA expression of Runx2 and type 1 collagen. Promoting osteogenic gene expression and enhancing mineral deposition on the prepared nanofiber show significant potential in accelerating bone healing and ensuring the successful integration of the scaffold with the surrounding bone tissue. Based on these findings, we conclude that the CS/GO@PAN nanofibrous membrane holds significant promise as a substrate for bone regeneration.

The increasing resistance of bacteria to antibiotics has become a serious threat to existing options for treating bacterial infections. We have developed a synthetic methodology for 3-sulfenyl pyrazolo[1,5-a]pyrimidines with potent antibacterial activity. This iodine-catalyzed strategy has been developed by employing amino pyrazoles, enaminones/chalcones, and thiophenols through intermolecular cyclization and subsequent cross-dehydrogenative sulfenylation. This highly regioselective and practicable protocol has been utilized to synthesize structurally diverse 3-sulfenyl pyrazolo[1,5-a]pyrimidines with wide functionalities. This strategy is also extendable toward the synthesis of bis(pyrazolo[1,5-a]pyrimidin-3-yl)sulfanes from amino pyrazole, enaminones/chalcone, and KSCN and the synthesis of 3-sulfenyl pyrazolo[1,5-a]pyrimidine from direct acetophenone. Mechanistic investigation disclosed a radical pathway for C–H sulfenylation and the involvement of 3-iodo pyrazolo[1,5-a]pyrimidine as the active intermediate. The biological investigation disclosed the potent antibacterial activity of sulfenyl pyrazolo[1,5-a]pyrimidines against Pseudomonas aeruginosa and Staphylococcus aureus, whereas pyrazolo[1,5-a]pyrimidine and sulfinyl pyrazolo[1,5-a]pyrimidine have no such antibacterial activity. Sulfenyl pyrazolo[1,5-a]pyrimidines mechanistically inhibited bacterial growth by the accumulation of ROS as well as induction in lipid peroxidation. Subsequently, such circumstances changed the membrane potential and facilitated the interaction with membrane-associated proteins, leading to a loss in membrane integrity and damage to bacterial cell membranes. Moreover, these derivatives potentiated the antibacterial efficacy of the commercial antibiotic ciprofloxacin against the selected bacterial strains and can be considered an alternative therapy against these bacterial infections.

A titanium alloy is widely used in implants for its excellent mechanical properties and corrosion resistance. However, the bonding strength between a titanium alloy and bone tissue is low, and the bacterial adhesion is easily triggered on the implant surface, which may cause the failure of implants. Therefore, surface modification is necessary to improve the biological activity and antibacterial properties. In this work, four different types of laser-induced periodic surface structure (LIPSS) surfaces are designed and fabricated on the TiNi alloy by a femtosecond laser according to the size of MC3T3-E1 mouse embryonic osteoblasts. The in vitro osteogenic activity of the LIPSS surface is investigated. It is found that the LIPSS helps improve the in vitro osteogenic activity, and bonelike apatite tends to deposit and distribute on the LIPSS. The biological activity and antibacterial activity of the LIPSS surface are evaluated through cell culture experiments and Escherichia coli culture experiments. It is demonstrated that the horizontal LIPSS sample with a width of 30 μm has the highest cell proliferation rate (142.5% after 1 day, 132.3% after 3 days) and a good antibacterial rate (50.2%). These results provide guidance for the application of the LIPSS in biocompatibility and antibacterial aspects.

Taking the potential applications of two-dimensional transition metal carbides, such as MXenes, in biomedical fields, it is crucial to explore the impact of MXenes on various blood proteins. The study of the interaction of these 2D materials with proteins is scarce. Owing to the potential of absorbing proteins on the MXene surface, it is crucial to investigate the biocompatibility of these materials with proteins . In this regard, we successfully investigated the biomolecular interactions between hemoglobin (Hb) and single-layered titanium carbide (Ti₃C₂T_x-SL), multilayered titanium carbide (Ti₃C₂T_x-ML), and multilayered vanadium carbide (V₂CT_x-ML) MXenes for protein-MXene corona formation. The conformational, thermal, and colloidal stabilities of Hb were investigated after exposing MXenes to Hb for 30 min at Hb/MXene ratios of 12:1, 10:1, 8:1, and 6:1 using a combination of spectroscopic techniques, electron microscopy, and thermodynamic stability studies. Our results reveal that Hb adsorption onto MXene surfaces is primarily driven by electrostatic interactions and hydrogen bonding, leading to significant changes in the secondary and tertiary structures of the protein and further disruption in the colloidal stability of Hb. Explicitly, the hierarchy of interactions between Hb and MXenes follows the order: Ti₃C₂T_x-SL > V₂CT_x-ML > Ti₃C₂T_x-ML. The morphological study of Hb with MXenes was studied through transmission electron microscopy (TEM) and atomic force microscopy (AFM). Further, it was found that at high loading concentrations that is above 8:1, the protein-corona formation tendency of Hb-MXene also increases. The biological and toxicological behavior of nanomaterials (NMs) is based on the effect of their interaction with proteins, which induces conformational changes in proteins and subsequently alters their biological functions. In this regard, this article provides important insights for using these MXenes biomedically and for the rational design of nanoproducts based on MXenes in the near future.

Designing advanced biomimetic nanoplatforms that combine photothermal therapy (PTT) and immune activation represents a modern approach to addressing the challenges of cancer therapy. This study presents a nanobiomimetic hollow copper-sulfide (HCuS) platform for precise homotypic tumor targeting and melanoma treatment. The HCuS@OVA@CM (COC) nanoplatform-encapsulated ovalbumin (OVA) antigen protein within HCuS nanoparticles and was coated with melanoma cell membranes (B16F10). Importantly, this design facilitates specific tumor accumulation and achieves 16.0% photothermal conversion efficiency under 1064 nm NIR-II irradiation, which is a key factor for therapeutic success. In vitro studies have demonstrated that this nanoplatform induces immunogenic cell death (ICD), enhances antigen presentation, and stimulates dendritic cell (DCs) maturation. In vivo experiments confirmed that COC-mediated NIR-II photothermal treatment significantly suppressed tumor growth without notable body weight loss. This biomimetic nanoplatform approach offers a targeted, enhanced, and effective immune response for tumor photothermal immunotherapy, making it a promising candidate for advanced melanoma treatment and anticancer therapy.

Interferon-gamma (IFN-γ), an essential inflammatory cytokine, is intricately associated with a variety of fatal diseases as a key early biomarker. In this work, we designed and constructed an electrochemical aptasensor based on topological insulator Bi₂Se₃ sheets. Micron-scale Bi₂Se₃ sheets were prepared by electrochemical exfoliation from single crystals to make electrodes of the aptasensors. The unique and robust Dirac surface states of Bi₂Se₃ could enhance the charge transfer efficiency of the solid–liquid interface, improving the performance of the aptasensors. The developed aptasensor exhibits a linear response to IFN-γ concentration in the range of 1–100 pg/mL with a detection limit as low as 0.6 pg/mL, enabling it to meet the clinical requirements. The performance of the aptasensors also shows excellent stability and selectivity. Furthermore, the aptasensor was applied to human serum detection and was comparable in performance to the clinical standard enzyme-linked immunosorbent assay technique. Our work indicates that the aptasensor based on Bi₂Se₃ sheets has great potential for application in the clinical detection of IFN-γ and other possible biomarkers.

Chemodynamic therapy (CDT), which utilizes transition metal ions to catalyze Fenton-like reactions for the eradication of tumor cells, has attracted substantial attention in the field of nanocatalysis. However, the therapeutic efficacy of CDT as a monotherapy is often limited by an insufficient level of hydrogen peroxide (H₂O₂) and the overexpressed glutathione (GSH) within tumor cells. Because of the high copper content in tumor tissues, a copper ionophore was strategically employed to enhance the intracellular accumulation of copper, thereby potentiating the CDT effect. Additionally, bovine serum albumin (BSA) was used to modify the copper ionophore, naphthazarin (Nap), to promote its targeting efficacy for tumor cells and to ensure its biosafety. The BSA-coated Nap nanoparticles, which could recruit Cu²⁺ in situ, were further deposited onto the surface of a manganese carbonate nanocube (Nap-BM NPs). The synergistic action of copper and manganese ions accelerated the decomposition of H₂O₂ into hydroxyl radicals (•OH) and consumed intracellular GSH, leading to cellular mortality via mitochondrial pathways. With low cytotoxicity and good biocompatibility in normal cells, the developed Nap-BM NPs significantly enhanced therapeutic outcomes by leveraging multiple Fenton-like reaction mechanisms to augment CDT, offering promising potential for clinical applications and contributing valuable insights into the field.

This study investigates the use of bimetallic copper–silver nanoclusters (Cu-AgNCs) for fluorescence turn-on sensing of leucine, a potential biomarker for cancer detection. These nanoclusters exhibit high fluorescence tunability and specificity, with Fe³⁺ serving as a quencher to facilitate leucine detection. The fluorescence recovery mechanism is attributed to the interaction of leucine with Fe³⁺, alleviating the quenching effect on the metal nanoclusters. This bimetallic nanocluster is a promising platform for biomarker identification in cancer diagnosis. The fluorescence enhancement upon leucine binding provides a measurable signal, confirming the feasibility of these nanoclusters as noninvasive sensors for cancer biomarkers. The sensor achieves a detection limit of 0.58 μM and demonstrates a linear response within the range of 110–657 μM. This approach offers a promising method for noninvasive cancer diagnostics using saliva and urine samples. Additionally, the method’s reproducibility and robustness further support its potential in clinical applications, providing a cost-effective and accessible technique for early cancer detection.

This study explores cell death through photodynamic therapy (PDT) with β-cyclodextrin-encapsulated platinum(II)-based nanoparticles (Pt-NPs) and the effect on the NF-κB and stress pathways in glioblastoma. The encapsulation of the cyclometalated Pt(II) complex Pt(LL′) within β-cyclodextrin (β-CD) enhances its biocompatibility, improves cellular penetration, and boosts emission, thereby increasing the effectiveness of PDT. Both Pt(LL′) and Pt-NPs show minimal toxicity in the dark; however, Pt-NPs significantly increase toxicity toward glioblastoma Kr158 cells upon irradiation at 390 nm. The PDT-induced cell death is further validated through apoptosis assays and the modulation of some key survival pathways like NF-κB/p65, DJ-1, and ERp29. This is the first report of β-cyclodextrin-encapsulated platinum(II)-based nanoparticles designed to target glioblastoma cells through PDT, offering a promising strategy for enhancing therapeutic efficacy.

Dramatic changes in climate and soil environments have made growing conditions for crops more challenging. These crops are subject to a range of abiotic stresses in different environments, which can lead to significant yield losses, resulting in economic and environmental damages. Herein, we report a straightforward one-pot hydrothermal method for creating carbon dots codoped with copper and nitrogen (Cu,N-CDs). Under salt stress conditions, Cu,N-CDs demonstrate the ability to alleviate oxidative damage in cucumber seedlings by modulating antioxidant defense mechanisms and scavenging reactive oxygen species (ROS). Cucumber seedling biomass accumulation is greatly enhanced by Cu,N-CDs treatment in the presence of a ROS burst, leading to a notable rise in the dry weight, plant height, and fresh weight. Cu,N-CDs mitigate oxidative damage in cucumber seedlings by activating antioxidant defense systems, specifically enhancing the activities of superoxide dismutase (+34.08%), catalase (+28.11%), peroxidase (+17.54%), and ascorbate peroxidase (+31.54%) to scavenge ROS. Furthermore, Cu,N-CDs can enhance the levels of nonenzymatic elements within the antioxidant system, such as polyphenols (+23.60%), flavonoids (+15.43%), and carotenoid content (+51.73%), which strengthen the scavenging ability of cucumber seedlings against ROS. Meanwhile, Cu,N-CDs can induce a significant increase of soluble sugar and soluble protein content by 27.27 and 32.58%, respectively, which improves the osmotic pressure as well as stress tolerance of plants. Additionally, the accumulation of biomass was aided by the increase in the photosynthetic pigment content that Cu,N-CDs treatment can produce.

Melanoma is a highly aggressive and metastatic malignancy, where current treatment methods often result in damage to healthy tissues, suboptimal therapeutic outcomes, and immune-related side effects. Microneedles, as a drug delivery system, offer advantages such as localized administration, minimal invasiveness, and high delivery efficiency. In this study, we first synthesized tetradecyl-thiol-grafted PAMAM dendrimers, which significantly enhanced cellular uptake and enabled sustained release of doxorubicin (DOX), improving cumulative drug release efficiency. Based on this, we developed a core–shell structured zwitterionic polymer-based microneedle delivery system. The outer shell, loaded with the photothermal agent indocyanine green (ICG), achieved precise photothermal therapy under near-infrared irradiation, effectively targeting melanoma tissues. The inner core, composed of a zwitterionic polymer matrix, encapsulated DOX-loaded dendrimers, enabling controlled and prolonged drug release through gradual polymer swelling and dendrimer expansion. Experiments show that the microneedle drug delivery system based on PAMAM dendrimer grafted with tetradecyl mercaptan and zwitterionic polymer has excellent anti protein adsorption properties, and it can minimize the cytotoxicity of carrier and improve the efficiency of drug delivery. This system effectively inhibited tumor growth through synergistic photothermal-chemotherapy, reducing systemic toxicity and improving drug bioavailability. This microneedle platform provides a promising strategy for targeted and synergistic melanoma therapy, offering a high-efficiency and low-toxicity treatment alternative.

Despite advances in surgical techniques for tendon injuries and improvements in rehabilitation, the challenge of achieving sufficient tendon regeneration and preventing postoperative tissue adhesions persists for orthopedic surgeons. In this study, we developed a multilayer film with a platelet-derived growth factor-BB (PDGF-BB)-immobilized leaf-stacked structure (LSS) layer (bioactive layer) and an alginate layer (antiadhesive layer) on both sides of a PCL film (PDGF/FLSS-Alg). The porous LSS layer on the PCL film was fabricated using a heating–cooling method with tetraglycol, where PDGF-BB was adsorbed onto the LSS layer. An alginate coating was applied on the opposite side to form the antiadhesion layer. The PDGF-BB loaded on the LSS layer provided a sustained release at effective concentrations for over 29 days. From in vitro cell culture and in vivo animal studies, the alginate layer proved effective in preventing cell/tissue adhesion; meanwhile, the bioactive layer facilitated tenogenic differentiation in hBMSCs and supported tendon regeneration. Accordingly, we propose that PDGF/FLSS-Alg offers a viable strategy for effective tendon regeneration in clinical practice.

Chronic ulcers present numerous challenges in treatment such as prolonged inflammation, infections resistant to drugs, and the formation of scars. In this research, we developed a calcium ion (Ca²⁺) cross-linked alginate (Alg) hydrogel loaded with CuO nanosheet/fibroblast cells via a microfluidic system with substantial efficiency in accelerating healing and preventing infection. Initially, the soft lithography method was utilized to fabricate the microfluidic system, which was employed to produce alginate hydrogel incorporating nanosheets of copper oxide (CuO) and MEF cells. The properties of hydrogel and copper oxide nanosheets were analyzed by using FE-SEM, EDS/EDX, and elemental mapping to determine their physicochemical characteristics. The viability of mouse embryonic fibroblast cells (MEF) in alginate–CuO hydrogel was explored through cell viability assay, and the antibacterial properties were also studied using colony-forming assay. The healing abilities of the hydrogel were investigated using an excisional, full-thickness wound rat model. Our results revealed proper antimicrobial and angiogenic properties with slight cytotoxicity for CuO nanosheets at a concentration of 25 μg/mL. The alginate–CuO-cell-treated group exhibited a faster wound contraction and healing among all treatments. The results of the in vivo assay along with histology and gene expression indicate a synergistic cooperation between MEF and CuO, leading to enhanced re-epithelialization, angiogenesis, and matrix remodeling. In this research, a therapeutic hydrogel with qualities like microbicidal, angiogenic, immune system modulation, and promotion of ECM and epithelium regeneration, resulting in faster healing, was developed. Moreover, there was a synergic impact noticed between CuO nanosheets and MEF cells as well as improved formation of blood vessels and collagen accumulation. In conclusion, this biocompatible hydrogel offers a promising strategy for effective wound healing without the need for invasive procedures.

Magnesium (Mg) and its alloys, as next-generation materials for anastomosis staples, offer promising advantages such as biodegradability, biocompatibility, and reduced risk of long-term complications compared to traditional titanium materials. However, the performance of biodegradable staples is highly dependent on their structure. In this study, a biodegradable high-purity (HP) Mg staple with an optimized structure intended for small intestine anastomosis was developed and evaluated in vitro. The designed staple, with a diameter of 0.3 mm, featured an interior angle of 100° and a height of 3.8 mm. This design exhibited a maximum effective stress of approximately 170 MPa and an effective strain of 1.63. The staple could maintain structural integrity without fracture after 7 days of in vitro corrosion testing and exhibited a relatively high burst pressure of approximately 54.70 ± 2.51 mmHg. These findings indicate that the newly designed HP Mg staple combines superior corrosion resistance and anastomosis strength, confirming its potential for clinical application.

The COVID-19 pandemic has created a need to develop protective textiles that reduce the infection of SARS-CoV-2, mainly via face masks. The key issue in designing protective textiles is the functionalization with antiviral agents. This report presents tin oxide nanoparticles (SnO₂NPs) as a novel, efficient antiviral agent against human coronavirus HCoV 229E due to blocking virus entry, attachment, and penetration into MRC-5 cells and nontoxicity. SnO₂NPs were obtained by sodium stannate hydrolysis and have a 3 nm diameter, a cubic structure, and a zeta potential of −28.8. SnO₂NPs were applied to functionalize a protective face mask made of silk fibroin. Polydopamine was applied to immobilize the particles. SnO₂NPs have a negative potential and enhance silk fabric hydrophobicity, which is crucial for antiviral properties. The mask functionalized with SnO₂NPs reveals very good antiviral properties and antibacterial activity against Gram-positive and -negative bacteria. Silk fabric functionalized with SnO₂NPs retains the silk fibroin β-sheet structure, is nontoxic, noncorrosive to human skin, and reveals high thermophysiological wear comfort.The highest filtration efficiency is obtained for the 3-layered mask (60%), while breathing resistance, sufficient for the FFP3 mask, was achieved for the 1-layered mask (maximum allowable breathing of 100 and 300 Pa, respectively, for 30 L/min and 95 L/min inhale and 300 Pa for an exhale flow rate of 160 L/min). SnO₂NPs can be useful in developing advanced antiviral textile materials to control virus spread and future pandemics.

Development of nanoplatforms with in situ activation for chemotherapy represents a promising modality for biomedical application. Herein, a multifunctional nanoplatform, CMS@DTC@PDA@RuNO@FA (abbreviated as CDPNF NPs), was developed for highly efficient antitumor therapy, in which diethyldithiocarbamate (DTC)-loaded mesoporous Cu₂MoS₄ (CMS) nanoparticles were covered by polydopamine (PDA) layers and further covalently modified with a NO donor (RuNO) and a folic acid (FA)-directing moiety. Under the mild acidic tumor microenvironment (TME), the CDPNF NPs co-liberated DTC and Cu²⁺ in the tumor site, where in situ formation of the highly cytotoxic Cu(DTC)₂ complex effectively killed tumor cells. Furthermore, under near-infrared (NIR) light irradiation, the CDPNF NPs could deliver nitric oxide (NO) and produce superoxide anions (O₂^•–), followed by the formation of more toxic peroxynitrite (ONOO^–), which led to promoted cell apoptosis. Under 1064 nm NIR light irradiation, in vivo experiments with CDPNF NPs demonstrated an impressively high tumor inhibition rate (∼97%) while with good biocompatibility. This work represents an in situ activated approach for precision medicine that might imply its promising potential for clinical applications.

The widespread occurrence of amyloidosis in many neurodegenerative diseases, including Alzheimer’s, highlights the urgent need for early detection methods. Traditional approaches often fall short in sensitivity, specificity, and the ability to operate within complex biological matrices. Fluorescence spectroscopy, which leverages the unique properties of extrinsic fluorescence sensors, has emerged as a promising avenue for amyloid detection. Thioflavin-T (ThT), while extensively utilized, faces several disadvantages such as poor blood–brain barrier penetration, short emission wavelength, and lack of sensitivity to oligomeric protein aggregates. These limitations necessitate the development of improved amyloid probes with enhanced properties for the better detection and understanding of neurodegenerative diseases. In this context, YOPRO-1, a cyanine-based molecular rotor probe, has been identified as a potent amyloid fibril sensor characterized by its turn-on fluorescence response and specificity for amyloid fibrils over native protein forms. Utilizing a variety of spectroscopic techniques, including steady-state emission, ground-state absorption, time-resolved fluorescence, and molecular docking, we demonstrate the superior selectivity and sensitivity of YOPRO-1 for amyloid fibrils. The probe exhibits a remarkable 245-fold increase in fluorescence intensity upon binding to insulin fibrils, which is a common amyloid model. This capability facilitates its application in complex biological matrices, such as high-percentage human serum, which has rarely been demonstrated by previous amyloid sensing probes. Furthermore, the commercial availability of YOPRO-1 avoids the challenges associated with the synthesis of specific probes, thereby marking a significant advancement in amyloid detection methodologies. Our findings highlight the potential of YOPRO-1 as a versatile and effective tool for the early diagnosis of amyloid-related diseases, offering a foundation for future therapeutic and diagnostic applications.

The development of nanostructured ZnO (nano-ZnO) with tailored morphologies is critical for creating effective antibacterial materials. This study introduces a high-throughput platform for the in situ synthesis of PPC/nano-ZnO composites, enabling precise control over the morphology of nano-ZnO to optimize antibacterial performance. By leveraging electrospinning, heat treatment, and hydrothermal synthesis, we fabricated diverse nano-ZnO structures, including nanoparticles, nanorods, and nanoflowers, on PPC nanofiber membranes. The large experimental data set generated through high-throughput synthesis facilitated the creation of a phase diagram that correlates key synthetic parameters, such as Zn²⁺ concentration, heat treatment temperature, and hydrothermal conditions, with nano-ZnO morphology and antibacterial efficacy. Tailoring the morphology of nano-ZnO is essential for maximizing antibacterial activity, and our results demonstrate that nanorods exhibit the highest efficacy against Escherichia coli due to their enhanced surface area and physical penetration capabilities. Phase diagram analysis revealed that increased Zn precursor concentrations promoted the growth of rod- and flower-like structures, which were linked to superior antibacterial performance. The sample with the highest antibacterial efficacy showed a maximum inhibition zone of 17.88 mm. A mechanistic model suggests that the mechanical disruption of bacterial membranes by sharp nano-ZnO structures is a key contributor to antibacterial action. This work underscores the significance of morphology control in designing effective antibacterial nanomaterials and provides a systematic approach to optimizing their properties.

Photodynamic therapy (PDT) has been demonstrated to be an effective tool for cancer treatment. Seeking organelle-targeting photosensitizers (PSs) with robust reactive oxygen species (ROS) production is extremely in demand. Herein, we propose an aggregation-induced photosensitization strategy for effective PDT with osmium complexes. We designed and synthesized three osmium complexes (Os-Me, Os-tBu, and Os-Nonly) with ligands of different alkyl chains. In phosphate-buffered saline solution, the complex Os-Nonly formed a spherical aggregate with diameters of around 220 nm. The results from ROS assays indicate that Os-Nonly showed the highest efficiency in generating superoxide anions and singlet oxygen, demonstrating its role as a type I/II photosensitizer. Additionally, Os-Nonly specifically targeted lysosomes in 4T1 and MCF-7 cells, producing ROS in a sustained and efficient manner with high phototoxicity (IC₅₀ = 6.999 μM in MCF-7 cells), thereby inducing cancer cell death. In 4T1-tumor-bearing mice models, Os-Nonly effectively inhibited tumor growth with a minimal impact on normal organs.

Vaccine immunotherapy is paving the way for an effective long-term immune response and targeted destruction of tumor cells and shows promise as a leading strategy in tumor treatment. Nanoparticles are crucial in combining vaccine immunotherapy and photothermal therapy (PTT), generating local tumor thermal ablation, and triggering a powerful antitumor immune response that inhibits tumor recurrence. In this study, we designed a nanovaccine that combined PTT and immunotherapy for tumors using two-dimensional black phosphorus (BP) as a nanoplatform that was modified with maleimide poly(ethylene glycol) (PEG-MAL) and coated with tumor antigen proteins (BP-PEG-MAL@antigen). The BP-PEG-MAL@antigen nanovaccines displayed outstanding stability and biocompatibility due to the comodification of PEG and antigen proteins. The nanovaccines induced strong immune responses in vitro and in vivo that effectively inhibited orthotopic and bilateral tumor growth, prolonged survival time, and improved the survival rate of mice. In addition, the nanovaccines generated a long-term immune response and effectively inhibited tumor recurrence.

The development of nanomaterials with multienzyme activity for advanced sensing and biosensing assays has attracted attention. In this study, a Cu–Co bimetallic nitrogen-doped carbon catalyst (CoCu@NC) was synthesized. The prepared nanomaterials exhibit catalase- and oxidase-like mimicking activities by adjusting the pH. The catalase-like activity of the CoCu@NC was investigated by quenching of terephthalic acid (TA) fluorescence at pH 11 in the presence of H₂O₂, while its oxidase behavior was confirmed by oxidation of 3,3′,5,5′-tetramethylbenzidine (TMB) as chromogenic substrate in the presence of O₂ at pH 3. Furthermore, CoCu@NC’s oxidase-like activity was used successfully to detect hydroquinone (HQ) at a concentration range of 1–900 nM with a detection limit of 0.22 nM and the anticancer drug doxorubicin (DOX) with a wide linear response ranging from 5 fM to 200 pM and an exceptionally low detection limit of 1.66 fM by reduction of oxTMB to TMB. DOX interacts in situ with single-stranded (ssDNA) and double-stranded DNA (dsDNA), reducing the quinone ring in its structure to hydroquinone (HQ) and oxidizing guanine bases to 8-oxoguanine. Based on this phenomenon, we designed a label-free colorimetric sensor for measuring DNA damage (ranging from 1 pM to 1 μM), in which this sensor operates by the disappearance of the blue oxTMB solution and the presence of the DNA/DOX. Furthermore, this designed sensor is sensitive to the number of guanine bases in ssDNA and dsDNA. As the number of guanine bases (1–12) in DNA sequences increases, a greater color change is observed. Finally, in the presence of H₂O₂-induced DNA damage, no intercalation occurred between DOX and the DNA-damaged sequences, with the color change observable with the naked eye. Therefore, this visualization assay demonstrates a low-cost, simple, rapid, sensitive, and effective method for detecting DOX drug and damaged DNA. Additionally, CoCu@NC magnetic nanostructures could be easily recollected and reused by applying a magnetic field.

Bioactive and biodegradable fibrous conduits consisting of well-organized microfibers with longitudinal grooves on the fiber surface were prepared by electrospinning for nerve guidance conduit (NGC) application. Tubular constructs with uniaxially aligned topographical cues have great potential to enhance axonal regeneration and are needed to bridge large gaps between proximal and distal nerves. In this study, we developed electrospun NGCs using milk-derived casein protein (MDP) with biodegradable polycaprolactone and polylactic-co-glycolic acid. We designed and fabricated a biodegradable polymer for random fiber (RF), aligned fiber (AF), random fiber with MDP (MDP-RF), and aligned the fiber with MDP (MDP-AF) by using electrospinning. We hypothesized that topographically defined NGC as MDP-AF NGC would enhance axonal outgrowth by topographical cues and chemoattraction of the bioactive peptide in MDP for macrophage migration. The in vitro MDP-AF NGC results showed not only the promotion of a guidance effect on Schwann cell migration and macrophage polarization but also the enhancement of PC12 cell neurite outgrowth. Additionally, we demonstrated that the synergetic effects of the MDP-AF NGC enhanced the regeneration of injured sciatic nerves. To confirm the effect of MDP-AF NGC, we implanted it into a rat sciatic nerve (10 mm defect). The walking track analysis for sciatic function, electrophysiological test, gastrocnemius muscle weight, and histological and immunohistological analyses indicated that MDP-AF NGC effectively improved sciatic nerve regeneration compared with other groups at 4 and 8 weeks. Herein, we evolutionally developed MDP-AF NGC with geometric and chemotactic stimuli using an electrospinning method combined with a biocompatible synthetic polymer and bioactive casein protein.

The growing demand for renewable energy has positioned microalgae, such as Chlorella vulgaris, as a promising feedstock for sustainable biofuel production. Leveraging nanotechnology, this study explores the multifaceted impacts of zinc oxide (ZnO) nanoparticles (NPs) on C. vulgaris, focusing on lipid biosynthesis, oxidative stress, biomass productivity, and photosynthetic pigment retention. The morphology of NPs and algae and their interactions were extensively studied using scanning electron microscopy (SEM), confocal microscopy, energy-dispersive X-ray spectroscopy (EDS), and X-ray photoelectron spectroscopy (XPS). The ZnO NP-enabled microalgae system enhanced lipid accumulation to as high as 48% at 50 mg/L. Biomass production and pigment content remained stable within the applied dose of NPs (20–50 mg/L), highlighting the resilience of C. vulgaris under NP exposure. However, at 100 mg/L, photosynthetic efficiency was disrupted, pigment content was reduced, and lipid yield declined to 30%. The enzymatic activity of catalase (CAT) revealed significant upregulation at higher ZnO NP concentrations, further corroborating the stress-induced metabolic shifts. This study also introduced a model for the Biofuel Suitability Score (BSS), which integrates lipid content, biomass productivity, oxidative stress levels, and pigment retention to identify the optimal conditions for biofuel production. The BSS peaked at moderate ZnO NP concentrations (30–50 mg/L), indicating a balance between lipid biosynthesis and cellular integrity. Beyond this threshold, oxidative damage compromises the biofuel potential, emphasizing the critical need for precise control of NP exposure. These findings highlight the potential of ZnO NPs to induce lipid accumulation through targeted stress modulation while maintaining biomass quality, advancing the application of nanotechnology in sustainable bioenergy systems. This study provides a scalable framework for integrating nanotechnology into renewable energy.

Bismuth sulfide@bismuth nanorods (Bi₂S₃@Bi NRs) have emerged as promising photodynamic therapeutic agents due to Bi₂S₃@Bi being able to produce reactive oxygen species from self-supplied O₂. Combining photothermal and photodynamic therapies with chemotherapy is attractive but difficult to achieve. Here, we develop a subtle method to wrap Bi₂S₃@Bi NRs with photothermal mesoporous polydopamine, where chemotherapy drug doxorubicin hydrochloride can be loaded, thus providing multifunctional antitumor nanospheres. To our delight, the prepared triple-functional material exhibits excellent antitumor efficacy toward tumor cells under near-infrared light irradiation. This multifunctional antitumor nanomaterial is not only biocompatible but also suitable for tumor hypoxic microenvironments, having much better efficacy than single- or double-functional materials. This study highlights the great potential of combining photothermal, photodynamic, and chemotherapies.

Exosomes, small extracellular vesicles with compositions reflecting their cell of origin, serve as sensitive and specific biomarkers for disease detection. We herein report a protocol for rapid isolation and characterization of exosomes by a single-step and label-free protein biomarker analysis. Using a simple centrifugation-filtration-concentration (CFC) method, exosomes are isolated and enriched 50-fold from conditioned cell culture media. For protein biomarker analysis, unconjugated antibodies are added directly to the isolated exosome solution. The specific interaction between the antibodies and exosomes leads to aggregation of exosomes, and subsequently, an average particle size increase of the assay solution. This average particle size increase can be detected using dynamic light scattering and correlated to the presence or absence of protein biomarkers on the exosomes. In this study, exosomes from three cell types, human embryonic kidney (HEK293) cells, genetically modified HEK-GFP cells, and GBM/NSC CD133⁺ cells were isolated. The exosomes released from HEK293, HEK-GFP, and GBM/NSC CD133⁺ cells exhibited monodispersed size distributions with an average particle size centered around 70, 66, and 249 nm, respectively. Positive antibody binding to exosome surface proteins resulted in a peak shift, increasing particle size by 25, 32, and 148 nm, respectively, for the HEK293, HEK-GFP, and GBM/NSC CD133⁺ exosomes, while the size increase upon addition of a negative antibody remained minimum. This protocol provides a convenient platform for the design and development of rapid diagnostic tests targeting disease specific exosomes.

Messenger RNA (mRNA) has proven to be an effective vaccine agent against unexpected pandemics, offering the advantage of rapidly producing customized therapeutics targeting specific pathogens. However, undesired byproducts, such as double-stranded RNA (dsRNA), generated during in vitro transcription (IVT) reactions may impede translation efficiency and trigger inflammatory cytokines in cells after mRNA uptake. In this study, we developed a facile method using PEGylated polystyrene resins that were further surface-modified with graphene oxide (GO@PEG–PS) for the removal of dsRNA from IVT mRNA. The GO@PEG–PS resin adsorbed mRNA due to the property of graphene oxide (GO), which preferentially adsorbs single-stranded nucleic acids over double-stranded nucleic acids in the presence of Mg²⁺. The resin-bound single-stranded (ss) RNA was readily desorbed with a mixture of EDTA and urea, possibly by chelating Mg²⁺ and disrupting hydrogen bonding, respectively. Spin-column chromatography with GO@PEG–PS for IVT mRNA eliminated at least 80% of dsRNA, recovering approximately 85% of mRNA. Furthermore, this procedure precluded the salt precipitation step after the IVT reaction, which fractionates mRNAs from the IVT components, including nucleotides and enzymes. The purified mRNA exhibited enhanced protein translation with reduced secretion of interferon (IFN)-β upon mRNA transfection. We anticipate that the mRNA purification chromatography system employing GO@PEG–PS resin will facilitate the removal of dsRNA contamination during mRNA production.

Patterned assembly of multivalent antibody complexes using DNA nanostructure templates holds the potential for advancing studies of cellular signaling and smart theranostic applications. However, evaluating the heterogeneity in protein conjugation efficiency at distinct sites on DNA templates remains challenging. Here, we utilize atomic force microscopy to measure the coupling of antibodies at various positions on two-dimensional rectangular DNA origami frameworks at the single-molecule level, generating spatial maps of antibody binding efficiencies across the structures. We observe that a discrete distribution of docking sites (spacing of at least 18 nm) on the framework leads to a progressive decrease in the antibody coupling efficiency from the periphery toward the center. In contrast, a continuous distribution of docking sites (spacing of ∼10 nm) results in a higher efficiency at the center relative to the periphery. We reason that the two opposing trends result from trade-offs among Coulombic repulsion, steric hindrance, and multivalent cooperative effects. This study presents a quantitative evaluation tool for protein–DNA framework conjugates, providing insights into optimizing DNA framework-based systems for improved precision in diagnostics and therapeutic applications.

To combat escalating antibiotic resistance in titanium implant-associated infections, oxygen-vacancy-rich polydopamine/TiCu nanocoating (PDA/p-TiCu-300 °C) was developed on medical-grade titanium, uniquely enabling synergistic photothermal (PTT), photodynamic (PDT), and sonodynamic (SDT) antimicrobial strategies. Unlike previous dual-modal approaches, this trimodal strategy, activated by near-infrared light and ultrasound, achieved exceptional broad-spectrum bactericidal efficacy against both Escherichia coli (99.19% killing) and Staphylococcus aureus (95.03% killing) via enhanced reactive oxygen species (ROS) generation and membrane disruption. The engineered oxygen vacancies within the PDA/p-TiCu-300 °C nanocoating significantly boosted ROS production, outperforming conventional photocatalytic materials. Crucially, the nanocoatings demonstrated excellent in vitro cytocompatibility. This PTT–PDT–SDT platform exhibits synergistic multimodal bactericidal activity, overcoming the limitations of existing strategies and representing a paradigm shift in implant surface modification with significant translational potential against severe infections.