Pulmonary Toxicity of Boron Nitride Nanomaterials Is Aspect Ratio DependentClick to copy article linkArticle link copied!
- Luis Augusto Visani de LunaLuis Augusto Visani de LunaNanomedicine Lab, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester Academic Health Science Centre, Manchester M13 9PT, U.K.National Graphene Institute, The University of Manchester, Manchester, M13 9PL, U.K.Lydia Becker Institute of Immunology and Inflammation, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester Academic Health Science Centre, Manchester M13 9PT, U.K.More by Luis Augusto Visani de Luna
- Thomas LoretThomas LoretNanomedicine Lab, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester Academic Health Science Centre, Manchester M13 9PT, U.K.National Graphene Institute, The University of Manchester, Manchester, M13 9PL, U.K.Lydia Becker Institute of Immunology and Inflammation, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester Academic Health Science Centre, Manchester M13 9PT, U.K.More by Thomas Loret
- Yilin HeYilin HeCNRS, Immunology, Immunopathology and Therapeutic Chemistry, UPR 3572, University of Strasbourg, ISIS, 67000 Strasbourg, FranceMore by Yilin He
- Morgan LegnaniMorgan LegnaniCIRIMAT, Université Toulouse 3 Paul Sabatier, Toulouse INP, CNRS, Université de Toulouse, 118 Route de Narbonne, 31062 Toulouse cedex 9, FranceMore by Morgan Legnani
- Hazel LinHazel LinCNRS, Immunology, Immunopathology and Therapeutic Chemistry, UPR 3572, University of Strasbourg, ISIS, 67000 Strasbourg, FranceMore by Hazel Lin
- Anne Marie GalibertAnne Marie GalibertCIRIMAT, Université Toulouse 3 Paul Sabatier, Toulouse INP, CNRS, Université de Toulouse, 118 Route de Narbonne, 31062 Toulouse cedex 9, FranceMore by Anne Marie Galibert
- Alexander FordhamAlexander FordhamNanomedicine Lab, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester Academic Health Science Centre, Manchester M13 9PT, U.K.National Graphene Institute, The University of Manchester, Manchester, M13 9PL, U.K.Lydia Becker Institute of Immunology and Inflammation, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester Academic Health Science Centre, Manchester M13 9PT, U.K.More by Alexander Fordham
- Sonja HolmeSonja HolmeNanomedicine Lab, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester Academic Health Science Centre, Manchester M13 9PT, U.K.National Graphene Institute, The University of Manchester, Manchester, M13 9PL, U.K.Lydia Becker Institute of Immunology and Inflammation, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester Academic Health Science Centre, Manchester M13 9PT, U.K.More by Sonja Holme
- Antonio Esau Del Rio CastilloAntonio Esau Del Rio CastilloBeDimensional S.p.A., Lungo Torrente Secca 30r, 16163 Genoa, ItalyMore by Antonio Esau Del Rio Castillo
- Francesco BonaccorsoFrancesco BonaccorsoBeDimensional S.p.A., Lungo Torrente Secca 30r, 16163 Genoa, ItalyIstituto Italiano di Tecnologia, Graphene Laboratories, Via Morego 30, 16163 Genoa, ItalyMore by Francesco Bonaccorso
- Alberto Bianco*Alberto Bianco*A.B.: email, [email protected]CNRS, Immunology, Immunopathology and Therapeutic Chemistry, UPR 3572, University of Strasbourg, ISIS, 67000 Strasbourg, FranceMore by Alberto Bianco
- Emmanuel Flahaut*Emmanuel Flahaut*E.F.: email, [email protected]CIRIMAT, Université Toulouse 3 Paul Sabatier, Toulouse INP, CNRS, Université de Toulouse, 118 Route de Narbonne, 31062 Toulouse cedex 9, FranceMore by Emmanuel Flahaut
- Kostas Kostarelos*Kostas Kostarelos*K.K.: email, [email protected]Nanomedicine Lab, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester Academic Health Science Centre, Manchester M13 9PT, U.K.National Graphene Institute, The University of Manchester, Manchester, M13 9PL, U.K.Catalan Institute of Nanoscience and Nanotechnology (ICN2), CSIC and BIST, Campus UAB, Bellaterra, 08193 Barcelona, SpainMore by Kostas Kostarelos
- Cyrill Bussy*Cyrill Bussy*C.B.: email, [email protected]Nanomedicine Lab, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester Academic Health Science Centre, Manchester M13 9PT, U.K.National Graphene Institute, The University of Manchester, Manchester, M13 9PL, U.K.Lydia Becker Institute of Immunology and Inflammation, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester Academic Health Science Centre, Manchester M13 9PT, U.K.More by Cyrill Bussy
Abstract
Boron nitride (BN) nanomaterials have drawn a lot of interest in the material science community. However, extensive research is still needed to thoroughly analyze their safety profiles. Herein, we investigated the pulmonary impact and clearance of two-dimensional hexagonal boron nitride (h-BN) nanosheets and boron nitride nanotubes (BNNTs) in mice. Animals were exposed by single oropharyngeal aspiration to h-BN or BNNTs. On days 1, 7, and 28, bronchoalveolar lavage (BAL) fluids and lungs were collected. On one hand, adverse effects on lungs were evaluated using various approaches (e.g., immune response, histopathology, tissue remodeling, and genotoxicity). On the other hand, material deposition and clearance from the lungs were assessed. Two-dimensional h-BN did not cause any significant immune response or lung damage, although the presence of materials was confirmed by Raman spectroscopy. In addition, the low aspect ratio h-BN nanosheets were internalized rapidly by phagocytic cells present in alveoli, resulting in efficient clearance from the lungs. In contrast, high aspect ratio BNNTs caused a strong and long-lasting inflammatory response, characterized by sustained inflammation up to 28 days after exposure and the activation of both innate and adaptive immunity. Moreover, the presence of granulomatous structures and an indication of ongoing fibrosis as well as DNA damage in the lung parenchyma were evidenced with these materials. Concurrently, BNNTs were identified in lung sections for up to 28 days, suggesting long-term biopersistence, as previously demonstrated for other high aspect ratio nanomaterials with poor lung clearance such as multiwalled carbon nanotubes (MWCNTs). Overall, we reveal the safer toxicological profile of BN-based two-dimensional nanosheets in comparison to their nanotube counterparts. We also report strong similarities between BNNTs and MWCNTs in lung response, emphasizing their high aspect ratio as a major driver of their toxicity.
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You are free to share(copy and redistribute) this article in any medium or format and to adapt(remix, transform, and build upon) the material for any purpose, even commercially within the parameters below:
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Introduction
Results and Discussion
Characterization and Clearance from the Lungs of h-BN and BNNTs
Synthesis and Characterization of the Boron Nitride Materials
Figure 1
Figure 1. Structural characterization of h-BN and BNNTs. (a) TEM image of h-BN. (b) AFM image of h-BN. (c,d) Lateral size (LogNorm. SD 0.797, N = 159) and thickness distributions (LogNorm. SD 1.054, N = 129) of h-BN nanosheets. (e) TEM image of BNNTs. (f) AFM image of BNNTs. (g) Diameter distribution of walls for BNNTs (black and red bars correspond to internal and external diameters, respectively). (h) Number of walls for BNNTs.
Evaluation of h-BN and BNNT Elimination from Lung Tissues Using Raman Spectroscopy
Figure 2
Figure 2. Evaluation of boron nitride distribution and clearance using scanning Raman spectroscopy. Mice were exposed by single oropharyngeal aspiration to 30 μg of h-BN or BNNTs. One, 7, and 28 days after the last exposure, left lungs were collected, inflated with formalin, embedded in paraffin, and then processed (n = 5). Lung sections (5 μm) were dewaxed and scanned using scanning Raman spectroscopy. h-BN and BNNTs were identified based on the Raman shift at 1370 cm–1. (a) Overlay of Raman intensities and bright-field images are presented. (b) Variation of boron (1370 cm–1) intensity over time.
Boron Nitride Nanomaterials Induced Inflammation Is Aspect Ratio Dependent
Impact on BAL Cell Populations
Figure 3
Figure 3. Influx of inflammatory cells in alveolar space. Mice were exposed by oropharyngeal aspiration to 30 μg of h-BN, BNNTs, or to control (vehicle and LPS). BALFs were collected on days 1, 7, and 28, cytospun on slides, and then differentially stained for cell phenotyping. (a) Cell population in BALFs. (b) Total number of immune cells. (c) Number of mononucleated macrophages, multinucleated macrophages, neutrophils, eosinophils, and lymphocytes in BALF. Two-way ANOVA followed by Tukey’s multiple comparisons test was used to evaluate statistical differences compared to the negative control (p < 0.05 (*), p < 0.01 (**), p < 0.001 (***)).
Expression of Inflammatory Markers in Lungs
Figure 4
Figure 4. Inflammatory response in lungs. (a) Evaluation of inflammatory markers levels in lungs by multiplex ELISA (log2 fold change). (I) Acute inflammation; (II) late pro-inflammatory response; (III) anti-inflammatory response; (IV) adaptive immune activation. (b) Evaluation of SAA3, Arg-1, and osteopontin levels by RT-qPCR. One-way ANOVA followed by Dunnett posthoc test was used to evaluate any statistical difference between normalized cytokine concentrations (pg/mg of total protein measured with Pierce Assay) or fold change compared to the negative control (n = 5; (*) p < 0.05, (**) p < 0.01, (***) p < 0.001).
Nanotubes but Not 2D Nanosheets Caused Lung Tissue Damage
Histological Changes
Figure 5
Figure 5. Histopathological changes in lungs. Mice were exposed to h-BN, BNNTs, or controls. (a) Lung sections were stained in hematoxylin and eosin for histopathological analysis. (b) Bronchial and pleural thicknesses were recorded. Immune infiltrates (green arrow), and granulomatous-like structures (yellow arrow) were identified and measured. Two-way ANOVA followed by Tukey’s multiple comparisons test was used to evaluate statistical differences between materials exposure and the negative control (n = 5; p < 0.05 (*), p < 0.01 (**), p < 0.001 (***)).
Evaluation of Fibrosis and Potential DNA Damage in the Lung Parenchyma
Figure 6
Figure 6. Fibrosis and DNA damage in the lungs. Mice were exposed to h-BN, BNNTs, or controls; lungs were collected after 28 days. (a) Lung sections were stained with Masson’s Trichrome, then collagen deposition was evaluated using MATLAB. (b) Lung sections from day 28 were immunostained for γ-H2AX to evaluate DNA double-strand breaks and potential long-term genotoxicity. One-way ANOVA followed by Dunett’s posthoc test was used to evaluate statistical differences between h-BN or BNNTs and the negative control (n = 5; p < 0.05 (*), p < 0.01 (**), p < 0.001 (***)).
Comparing the Pulmonary Impact of h-BN Nanosheets with Other 2D Materials
BNNT Impact in Lungs in Comparison to Other High Aspect Ratio Materials
Conclusion
Experimental Section
Materials Production
Materials Characterization
Animal Exposure
Collection of the Samples
Evaluation of Lung Clearance Using Raman Spectroscopy
BAL Fluid Analysis
Evaluation of the Inflammation Using Multiplex ELISA
Gene Expression by RT-qPCR
Histopathology of the Lungs
Evaluation of Collagen Deposition in the Lung Parenchyma
Evaluation of Potential Genotoxicity in the Lung Parenchyma Using γ-H2AX
Statistical Analysis
Supporting Information
The Supporting Information is available free of charge at https://pubs.acs.org/doi/10.1021/acsnano.3c06599.
Numerical results of XPS survey; RT-qPCR primers; physicochemical characteristics of BN materials; Raman, TGA, XPS analysis of the materials; representative pictures of BAL cells cytospun and differentially stained; AA protein measurement in blood samples (PDF)
Terms & Conditions
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Acknowledgments
This project has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement no. 881603 (H2020-FET-GrapheneCore3). A.F. acknowledges studentship cofunded by the Lloyds Register Foundation funded International Consortium on Nanotechnology (LRF-ICON) and the UK Research and Innovation Engineering and Physical Sciences Research Council (UKRI-EPSRC) Centre for Doctoral Training Programme Graphene NOWNANO (EP/L01548X/1). At the Faculty of Biology, Medicine, and Health, The University of Manchester, UK, we thank G. Balko (Histology Facility), Dr P. March (Bioimaging Facility), Dr N. Hodson (BioAFM Facility), and all staff in the Biological Services Facility. The microscopes of the Bioimaging and BioAFM Facilities used in the present study were purchased with grants from the UKRI Biotechnology and Biological Sciences Research Council (UKRI-BBSRC), the Wellcome Trust, and the University of Manchester Strategic Fund. This work was also supported by the Centre National de la Recherche Scientifique (CNRS), the Agence Nationale de la Recherche (ANR) through the LabEx project Chemistry of Complex Systems (ANR-10-LABX-0026_CSC), and by the Jean-Marie Lehn Foundation. We thank Cathy Royer from the “Plateforme Imagerie In Vitro de l’ITI Neurostra” CNRS UAR 3156, University of Strasbourg (Strasbourg, France) for TEM analysis. The ICN2 is funded by the CERCA Programme, Generalitat de Catalunya, and has been supported by the Severo Ochoa Centres of Excellence program [SEV-2017-0706] and is currently supported by the Severo Ochoa Centres of Excellence program [CEX2021-001214-S], both funded by MCIN/AEI/10.13039.501100011033. We thank the company BNNT LLC for providing the SP10RX sample of purified BNNTs.
References
This article references 66 other publications.
- 1Ferrari, A. C.; Bonaccorso, F.; Fal’ko, V.; Novoselov, K. S.; Roche, S.; Bøggild, P.; Borini, S.; Koppens, F. H. L.; Palermo, V.; Pugno, N. Science and Technology Roadmap for Graphene, Related Two-Dimensional Crystals, and Hybrid Systems. Nanoscale 2015, 7 (11), 4598, DOI: 10.1039/C4NR01600AGoogle Scholar1https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXhsFyhu77K&md5=65926c599802eaf69f8e1b3160cc0189Science and technology roadmap for graphene, related two-dimensional crystals, and hybrid systemsFerrari, Andrea C.; Bonaccorso, Francesco; Fal'ko, Vladimir; Novoselov, Konstantin S.; Roche, Stephan; Boeggild, Peter; Borini, Stefano; Koppens, Frank H. L.; Palermo, Vincenzo; Pugno, Nicola; Garrido, Jose A.; Sordan, Roman; Bianco, Alberto; Ballerini, Laura; Prato, Maurizio; Lidorikis, Elefterios; Kivioja, Jani; Marinelli, Claudio; Ryhanen, Tapani; Morpurgo, Alberto; Coleman, Jonathan N.; Nicolosi, Valeria; Colombo, Luigi; Fert, Albert; Garcia-Hernandez, Mar; Bachtold, Adrian; Schneider, Gregory F.; Guinea, Francisco; Dekker, Cees; Barbone, Matteo; Sun, Zhipei; Galiotis, Costas; Grigorenko, Alexander N.; Konstantatos, Gerasimos; Kis, Andras; Katsnelson, Mikhail; Vandersypen, Lieven; Loiseau, Annick; Morandi, Vittorio; Neumaier, Daniel; Treossi, Emanuele; Pellegrini, Vittorio; Polini, Marco; Tredicucci, Alessandro; Williams, Gareth M.; Hee Hong, Byung; Ahn, Jong-Hyun; Min Kim, Jong; Zirath, Herbert; van Wees, Bart J.; van der Zant, Herre; Occhipinti, Luigi; Di Matteo, Andrea; Kinloch, Ian A.; Seyller, Thomas; Quesnel, Etienne; Feng, Xinliang; Teo, Ken; Rupesinghe, Nalin; Hakonen, Pertti; Neil, Simon R. T.; Tannock, Quentin; Lofwander, Tomas; Kinaret, JariNanoscale (2015), 7 (11), 4598-4810CODEN: NANOHL; ISSN:2040-3372. (Royal Society of Chemistry)A review. We present the science and technol. roadmap for graphene, related two-dimensional crystals, and hybrid systems, targeting an evolution in technol., that might lead to impacts and benefits reaching into most areas of society. This roadmap was developed within the framework of the European Graphene Flagship and outlines the main targets and research areas as best understood at the start of this ambitious project. We provide an overview of the key aspects of graphene and related materials (GRMs), ranging from fundamental research challenges to a variety of applications in a large no. of sectors, highlighting the steps necessary to take GRMs from a state of raw potential to a point where they might revolutionize multiple industries. We also define an extensive list of acronyms in an effort to standardize the nomenclature in this emerging field.
- 2Roy, S.; Zhang, X.; Puthirath, A. B.; Meiyazhagan, A.; Bhattacharyya, S.; Rahman, M. M.; Babu, G.; Susarla, S.; Saju, S. K.; Tran, M. K. Structure, Properties and Applications of Two-Dimensional Hexagonal Boron Nitride. Adv. Mater. 2021, 2101589, DOI: 10.1002/adma.202101589Google Scholar2https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3MXitFamsL3I&md5=5b8700c618d1863245f70e6125db36cbStructure, Properties and Applications of Two-Dimensional Hexagonal Boron NitrideRoy, Soumyabrata; Zhang, Xiang; Puthirath, Anand B.; Meiyazhagan, Ashokkumar; Bhattacharyya, Sohini; Rahman, Muhammad M.; Babu, Ganguli; Susarla, Sandhya; Saju, Sreehari K.; Tran, Mai Kim; Sassi, Lucas M.; Saadi, M. A. S. R.; Lai, Jiawei; Sahin, Onur; Sajadi, Seyed Mohammad; Dharmarajan, Bhuvaneswari; Salpekar, Devashish; Chakingal, Nithya; Baburaj, Abhijit; Shuai, Xinting; Adumbumkulath, Aparna; Miller, Kristen A.; Gayle, Jessica M.; Ajnsztajn, Alec; Prasankumar, Thibeorchews; Harikrishnan, Vijay Vedhan Jayanthi; Ojha, Ved; Kannan, Harikishan; Khater, Ali Zein; Zhu, Zhenwei; Iyengar, Sathvik Ajay; Autreto, Pedro Alves da Silva; Oliveira, Eliezer Fernando; Gao, Guanhui; Birdwell, A. Glen; Neupane, Mahesh R.; Ivanov, Tony G.; Taha-Tijerina, Jaime; Yadav, Ram Manohar; Arepalli, Sivaram; Vajtai, Robert; Ajayan, Pulickel M.Advanced Materials (Weinheim, Germany) (2021), 33 (44), 2101589CODEN: ADVMEW; ISSN:0935-9648. (Wiley-VCH Verlag GmbH & Co. KGaA)A review. Hexagonal BN (h-BN) has emerged as a strong candidate for 2-dimensional (2D) material owing to its exciting optoelec. properties combined with mech. robustness, thermal stability, and chem. inertness. Super-thin h-BN layers have gained significant attention from the scientific community for many applications, including nanoelectronics, photonics, biomedical, anti-corrosion, and catalysis, among others. A systematic elaboration of the structural, elec., mech., optical, and thermal properties of h-BN followed by a comprehensive account of state-of-the-art synthesis strategies for 2D h-BN, including chem. exfoliation, chem., and phys. vapor deposition, and other methods that were developed in recent years is provided. It further elaborates a wide variety of processing routes developed for doping, substitution, functionalization, and combination with other materials to form heterostructures. Based on the extraordinary properties and thermal-mech.-chem. stability of 2D h-BN, various potential applications of these structures are described.
- 3Falin, A.; Cai, Q.; Santos, E. J. G.; Scullion, D.; Qian, D.; Zhang, R.; Yang, Z.; Huang, S.; Watanabe, K.; Taniguchi, T. Mechanical Properties of Atomically Thin Boron Nitride and the Role of Interlayer Interactions. Nat. Commun. 2017, 8, 15815, DOI: 10.1038/ncomms15815Google Scholar3https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXhtVCrt7zO&md5=ed5133678a75d0e8f9ea40ca54279028Mechanical properties of atomically thin boron nitride and the role of interlayer interactionsFalin, Aleksey; Cai, Qiran; Santos, Elton J. G.; Scullion, Declan; Qian, Dong; Zhang, Rui; Yang, Zhi; Huang, Shaoming; Watanabe, Kenji; Taniguchi, Takashi; Barnett, Matthew R.; Chen, Ying; Ruoff, Rodney S.; Li, Lu HuaNature Communications (2017), 8 (), 15815CODEN: NCAOBW; ISSN:2041-1723. (Nature Publishing Group)Atomically thin boron nitride (BN) nanosheets are important two-dimensional nanomaterials with many unique properties distinct from those of graphene, but investigation into their mech. properties remains incomplete. Here we report that high-quality single-cryst. mono- and few-layer BN nanosheets are one of the strongest elec. insulating materials. More intriguingly, few-layer BN shows mech. behaviors quite different from those of few-layer graphene under indentation. In striking contrast to graphene, whose strength decreases by more than 30% when the no. of layers increases from 1 to 8, the mech. strength of BN nanosheets is not sensitive to increasing thickness. We attribute this difference to the distinct interlayer interactions and hence sliding tendencies in these two materials under indentation. The significantly better interlayer integrity of BN nanosheets makes them a more attractive candidate than graphene for several applications, for example, as mech. reinforcements.
- 4Liu, Z.; Gong, Y.; Zhou, W.; Ma, L.; Yu, J.; Idrobo, J. C.; Jung, J.; Macdonald, A. H.; Vajtai, R.; Lou, J. Ultrathin Higherature Oxidation-Resistant Coatings of Hexagonal Boron Nitride. Nat. Commun. 2013, 4, 2541, DOI: 10.1038/ncomms3541Google Scholar4https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC2c%252FlvFGhsw%253D%253D&md5=489e725fdc37a25d1e2454ccd4ea053cUltrathin high-temperature oxidation-resistant coatings of hexagonal boron nitrideLiu Zheng; Gong Yongji; Zhou Wu; Ma Lulu; Yu Jingjiang; Idrobo Juan Carlos; Jung Jeil; MacDonald Allan H; Vajtai Robert; Lou Jun; Ajayan Pulickel MNature communications (2013), 4 (), 2541 ISSN:.Hexagonal boron nitride is a two-dimensional layered material that can be stable at 1,500 °C in air and will not react with most chemicals. Here we demonstrate large-scale, ultrathin, oxidation-resistant coatings of high-quality hexagonal boron nitride layers with controlled thicknesses from double layers to bulk. We show that such ultrathin hexagonal boron nitride films are impervious to oxygen diffusion even at high temperatures and can serve as high-performance oxidation-resistant coatings for nickel up to 1,100 °C in oxidizing atmospheres. Furthermore, graphene layers coated with a few hexagonal boron nitride layers are also protected at similarly high temperatures. These hexagonal boron nitride atomic layer coatings, which can be synthesized via scalable chemical vapour deposition method down to only two layers, could be the thinnest coating ever shown to withstand such extreme environments and find applications as chemically stable high-temperature coatings.
- 5Li, L. H.; Chen, Y. Atomically Thin Boron Nitride: Unique Properties and Applications. Adv. Funct. Mater. 2016, 26 (16), 2594– 2608, DOI: 10.1002/adfm.201504606Google Scholar5https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28XisFKhu7w%253D&md5=fa274a0a9feec8a58dd3bcfc22374536Atomically Thin Boron Nitride: Unique Properties and ApplicationsLi, Lu Hua; Chen, YingAdvanced Functional Materials (2016), 26 (16), 2594-2608CODEN: AFMDC6; ISSN:1616-301X. (Wiley-VCH Verlag GmbH & Co. KGaA)Atomically thin boron nitride (BN) is an important 2D nanomaterial, with many properties distinct from graphene. In this feature article, these unique properties and assocd. applications, often not feasible with graphene, are outlined. The article starts with characterization and identification of atomically thin BN. It is followed by demonstrating their strong oxidn. resistance at high temps. and applications in protecting metals from oxidn. and corrosion. As flat insulators, BN nanosheets are ideal dielec. substrates for surface enhanced Raman spectroscopy (SERS) and electronic devices based on 2D heterostructures. The light emission of BN nanosheets in the deep UV (DUV) and UV regions is also included for its scientific and technol. importance. The last part is dedicated to synthesis, characterization, and optical properties of BN nanoribbons, a special form of nanosheets.
- 6Cai, Q.; Du, A.; Gao, G.; Mateti, S.; Cowie, B. C. C.; Qian, D.; Zhang, S.; Lu, Y.; Fu, L.; Taniguchi, T. Molecule-Induced Conformational Change in Boron Nitride Nanosheets with Enhanced Surface Adsorption. Adv. Funct. Mater. 2016, 26 (45), 8202– 8210, DOI: 10.1002/adfm.201603160Google Scholar6https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28XhsVaksbvL&md5=4e422ad215b9acf0672223e761fffeedMolecule-Induced Conformational Change in Boron Nitride Nanosheets with Enhanced Surface AdsorptionCai, Qiran; Du, Aijun; Gao, Guoping; Mateti, Srikanth; Cowie, Bruce C. C.; Qian, Dong; Zhang, Shuang; Lu, Yuerui; Fu, Lan; Taniguchi, Takashi; Huang, Shaoming; Chen, Ying; Ruoff, Rodney S.; Li, Lu HuaAdvanced Functional Materials (2016), 26 (45), 8202-8210CODEN: AFMDC6; ISSN:1616-301X. (Wiley-VCH Verlag GmbH & Co. KGaA)Surface interaction is extremely important to both fundamental research and practical application. Physisorption can induce shape and structural distortion (i.e., conformational changes) in macromol. and biomol. adsorbates, but such phenomena have rarely been obsd. on adsorbents. Here, it is demonstrated theor. and exptl. that atomically thin boron nitride (BN) nanosheets as an adsorbent experience conformational changes upon surface adsorption of mols., increasing adsorption energy and efficiency. The study not only provides new perspectives on the strong adsorption capability of BN nanosheets and many other two-dimensional (2D) nanomaterials but also opens up possibilities for many novel applications. For example, it is demonstrated that BN nanosheets with the same surface area as bulk hexagonal BN particles are more effective in purifn. and sensing.
- 7Kim, J. H.; Pham, T. V.; Hwang, J. H.; Kim, C. S.; Kim, M. J. Boron Nitride Nanotubes: Synthesis and Applications. Nano Convergence. 2018, 17, DOI: 10.1186/s40580-018-0149-yGoogle Scholar7https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1cXhvV2lt7rO&md5=3cb832818fe56dbed4f1be15ad46af28Boron nitride nanotubes: synthesis and applicationsKim, Jun Hee; Pham, Thang Viet; Hwang, Jae Hun; Kim, Cheol Sang; Kim, Myung JongNano Convergence (2018), 5 (1), 17/1-17/13CODEN: NCAOCX; ISSN:2196-5404. (SpringerOpen)Boron nitride nanotube (BNNT) has similar tubular nanostructure as carbon nanotube (CNT) in which boron and nitrogen atoms arranged in a hexagonal network. Owing to the unique at. structure, BNNT has numerous excellent intrinsic properties such as superior mech. strength, high thermal cond., elec. insulating behavior, piezoelec. property, neutron shielding capability, and oxidn. resistance. Since BNNT was first synthesized in 1995, developing efficient BNNT prodn. route has been a significant issue due to low yield and poor quality in comparison with CNT, thus limiting its practical uses. However, many great successes in BNNT synthesis have been achieved in recent years, enabling access to this material and paving the way for the development of promising applications. In this article, we discussed current progress in the prodn. of boron nitride nanotube, focusing on the most common and effective methods that have been well established so far. In addn., we presented various applications of BNNT including polymer composite reinforcement, thermal management packages, piezo actuators, and neutron shielding nanomaterial.
- 8Zhan, Y.; Lago, E.; Santillo, C.; Del Río Castillo, A. E.; Hao, S.; Buonocore, G. G.; Chen, Z.; Xia, H.; Lavorgna, M.; Bonaccorso, F. An Anisotropic Layer-by-Layer Carbon Nanotube/Boron Nitride/Rubber Composite and Its Application in Electromagnetic Shielding. Nanoscale 2020, 12 (14), 7782– 7791, DOI: 10.1039/C9NR10672CGoogle Scholar8https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXkvF2ksro%253D&md5=44f10394d87d1d646b3708bcc50e5b02An anisotropic layer-by-layer carbon nanotube/boron nitride/rubber composite and its application in electromagnetic shieldingZhan, Yanhu; Lago, Emanuele; Santillo, Chiara; Del Rio Castillo, Antonio Esau; Hao, Shuai; Buonocore, Giovanna G.; Chen, Zhenming; Xia, Hesheng; Lavorgna, Marino; Bonaccorso, FrancescoNanoscale (2020), 12 (14), 7782-7791CODEN: NANOHL; ISSN:2040-3372. (Royal Society of Chemistry)Multifunctional polymer composites with anisotropic properties are attracting interest as they fulfil the growing demand of multitasking materials. In this work, anisotropic polymer composites have been fabricated by combining the layer-by-layer (LBL) filtration method with the alternative assembling of carbon nanotubes (CNTs) and hexagonal boron nitride flakes (hBN) on natural rubber latex particles (NR). The layered composites exhibit anisotropic thermal and elec. conductivities, which are tailored through the layer formulations. The best composite consists of four layers of NR modified with 8 phr (parts per hundred rubber) CNTs (~ 7.4 wt%) and four alternate layers with 12 phr hBN (~ 10.7 wt%). The composites exhibit an electromagnetic interference (EMI) shielding effectiveness of 22.41 ± 0.14 dB mm-1 at 10.3 GHz and a thermal cond. equal to 0.25 W m-1 K-1. Furthermore, when the layered composite is used as an elec. thermal heater the surface reaches a stable temp. of ~ 103°C in approx. 2 min, with an input bias of 2.5 V.
- 9Ren, J.; Stagi, L.; Carbonaro, C. M.; Malfatti, L.; Casula, M. F.; Ricci, P. C.; Del Rio Castillo, A. E.; Bonaccorso, F.; Calvillo, L.; Granozzi, G. Defect-Assisted Photoluminescence in Hexagonal Boron Nitride Nanosheets. 2D Mater. 2020, 7, 045023, DOI: 10.1088/2053-1583/ababf0Google Scholar9https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXit1Sqs7rN&md5=5e75331fd8e7add20b14bd0ecda3c44eDefect-assisted photoluminescence in hexagonal boron nitride nanosheetsRen, Junkai; Stagi, Luigi; Carbonaro, Carlo Maria; Malfatti, Luca; Casula, Maria Francesca; Ricci, Pier Carlo; Del Rio Castillo, Antonio Esau; Bonaccorso, Francesco; Calvillo, Laura; Granozzi, Gaetano; Innocenzi, Plinio2D Materials (2020), 7 (4), 045023CODEN: DMATB7; ISSN:2053-1583. (IOP Publishing Ltd.)The development of functional optoelectronic applications based on hexagonal boron nitride nanosheets (h-BNNs) relies on controlling the structural defects. The fluorescent emission, in particular, has been obsd. to depend on vacancies and substitutional defects. In the present work, few-layer h-BNNs have been obtained by sonication-assisted liq.-phase exfoliation of their bulk counterpart. The as-prepd. samples exhibit a weak fluorescent emission in the visible range, centered around 400 nm. Tailored defects have been introduced by oxidn. in air at different temps. A significant increase in the fluorescent emission of the oxidated h-BNNs has been obsd. with max. emissive intensity for the samples treated at 300°C. A further increase in temps. (>300°C) dets. a quenching of the fluorescence. We investigated, by means of detailed microscopic and spectroscopic anal., the relationship between the optical properties and defects of h-BNNs. The investigation of the optical properties as a function of treatment temp. highlights the crit. role of hydroxyl groups created by the oxidn. process. Only h-BN exfoliated in water allows introducing OH groups with consequent enhancement of fluorescence emission.
- 10Kodali, V. K.; Roberts, J. R.; Shoeb, M.; Wolfarth, M. G.; Bishop, L.; Eye, T.; Barger, M.; Roach, K. A.; Friend, S.; Schwegler-Berry, D. Acute in Vitro and in Vivo Toxicity of a Commercial Grade Boron Nitride Nanotube Mixture. Nanotoxicology 2017, 11 (8), 1040– 1058, DOI: 10.1080/17435390.2017.1390177Google Scholar10https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXhslGksbrN&md5=fe4af51818e7798b7502e1f44dd6bc19Acute in vitro and in vivo toxicity of a commercial grade boron nitride nanotube mixtureKodali, Vamsi K.; Roberts, Jenny R.; Shoeb, Mohammad; Wolfarth, Michael G.; Bishop, Lindsey; Eye, Tracy; Barger, Mark; Roach, Katherine A.; Friend, Sherri; Schwegler-Berry, Diane; Chen, Bean T.; Stefaniak, Aleksandr; Jordan, Kevin C.; Whitney, Roy R.; Porter, Dale W.; Erdely, Aaron D.Nanotoxicology (2017), 11 (8), 1040-1058CODEN: NANOGK; ISSN:1743-5404. (Taylor & Francis Ltd.)Boron nitride nanotubes (BNNTs) are an emerging engineered nanomaterial attracting significant attention due to superior elec., chem. and thermal properties. Currently, the toxicity profile of this material is largely unknown. Com. grade BNNTs are composed of a mixt. (BNNT-M) of ∼50-60% BNNTs, and ∼40-50% impurities of boron and hexagonal boron nitride. We performed acute in vitro and in vivo studies with com. grade BNNT-M, dispersed by sonication in vehicle, in comparison to the extensively studied multiwalled carbon nanotube-7 (MWCNT-7). THP-1 wild-type and NLRP3-deficient human monocytic cells were exposed to 0-100 μg/mL and C57BL/6 J male mice were treated with 40 μg of BNNT-M for in vitro and in vivo studies, resp. In vitro, BNNT-M induced a dose-dependent increase in cytotoxicity and oxidative stress. This was confirmed in vivo following acute exposure increase in bronchoalveolar lavage levels of lactate dehydrogenase, pulmonary polymorphonuclear cell influx, loss in mitochondrial membrane potential and augmented levels of 4-hydroxynonenal. Uptake of this material caused lysosomal destabilization, pyroptosis and inflammasome activation, corroborated by an increase in cathepsin B, caspase 1, increased protein levels of IL-1β and IL-18 both in vitro and in vivo. Attenuation of these effects in NLRP3-deficient THP-1 cells confirmed NLRP3-dependent inflammasome activation by BNNT-M. BNNT-M induced a similar profile of inflammatory pulmonary protein prodn. when compared to MWCNT-7. Functionally, pretreatment with BNNT-M caused suppression in bacterial uptake by THP-1 cells, an effect that was mirrored in challenged alveolar macrophages collected from exposed mice and attenuated with NLRP3 deficiency. Anal. of cytokines secreted by LPS-challenged alveolar macrophages collected after in vivo exposure to dispersions of BNNT-M showed a differential macrophage response. The obsd. results demonstrated acute inflammation and toxicity in vitro and in vivo following exposure to sonicated BNNT-M was in part due to NLRP3 inflammasome activation.
- 11Xin, X.; Barger, M.; Roach, K. A.; Bowers, L.; Stefaniak, A. B.; Kodali, V.; Glassford, E.; Dunn, K. L.; Dunn, K. H.; Wolfarth, M. Toxicity Evaluation Following Pulmonary Exposure to an As-Manufactured Dispersed Boron Nitride Nanotube (BNNT) Material in Vivo. NanoImpact 2020, 19, 100235, DOI: 10.1016/j.impact.2020.100235Google ScholarThere is no corresponding record for this reference.
- 12Dong, J. Signaling Pathways Implicated in Carbon Nanotube-Induced Lung Inflammation. Frontiers in Immunology. 2020, 552613, DOI: 10.3389/fimmu.2020.552613Google Scholar12https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3MXlvFeqsrw%253D&md5=416f3f1414974e79cc4831bc91662f50Signaling pathways implicated in carbon nanotube-induced lung inflammationDong, JieFrontiers in Immunology (2020), 11 (), 552613CODEN: FIRMCW; ISSN:1664-3224. (Frontiers Media S.A.)A review. Inflammation is a tissue response to a variety of harmful stimuli, such as pathogens, irritants, and injuries, and can eliminate insults and limit tissue damage. However, dysregulated inflammation is recognized as a cause of many human diseases, exemplified by organ fibrosis and cancer. In this regard, inflammation-promoted fibrosis is commonly obsd. in human lung diseases, such as idiopathic pulmonary fibrosis and pneumoconiosis. Carbon nanotubes (CNTs) are a type of nanomaterials with unique properties and various industrial and com. applications. On the other hand, certain forms of CNTs are potent inducers of inflammation and fibrosis in animal lungs. Notably, acute inflammation is a remarkable phenotype elicited by CNTs in the lung during the early acute phase post-exposure; whereas a type 2 immune response is evidently activated and dominates during the late acute and chronic phases, leading to type 2 inflammation and lung fibrosis. Numerous studies demonstrate that these immune responses involve distinct immune cells, various pathol. factors, and specific functions and play crucial roles in the initiation and progression of inflammation and fibrosis in the lung exposed to CNTs. Thus, the mechanistic understanding of the immune responses activated by CNTs has drawn great attention in recent years. This article reviews the major findings on the cell signaling pathways that are activated in immune cells and exert functions in promoting immune responses in CNT-exposed lungs, which would provide new insights into the understanding of CNT-induced lung inflammation and inflammation-driven fibrosis, the application of CNT-induced lung inflammation and fibrosis as a new disease model, and the potential of targeting immune cells as a therapeutic strategy for relevant human lung diseases.
- 13Dong, J.; Ma, Q. Type 2 Immune Mechanisms in Carbon Nanotube-Induced Lung Fibrosis. Frontiers in Immunology. 2018, 9, 1120, DOI: 10.3389/fimmu.2018.01120Google Scholar13https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1cXit1GjsLfM&md5=f6f896b5fd8985b3a879cadd64d5eaf7Type 2 immune mechanisms in carbon nanotube-induced lung fibrosisDong, Jie; Ma, QiangFrontiers in Immunology (2018), 9 (), 1120/1-1120/17CODEN: FIRMCW; ISSN:1664-3224. (Frontiers Media S.A.)A review. T helper (Th) 2-dependent type 2 immune pathways have been recognized as an important driver for the development of fibrosis. Upon stimulation, activated Th2 immune cells and type 2 cytokines interact with inflammatory and tissue repair functions to stimulate an overzealous reparative response to tissue damage, leading to organ fibrosis and destruction. In this connection, type 2 pathways are activated by a variety of insults and pathol. conditions to modulate the response. Carbon nanotubes (CNTs) are nanomaterials with a wide range of applications. However, pulmonary exposure to CNTs causes a no. of pathol. outcomes in animal lungs, dominated by inflammation and fibrosis. These findings, alongside the rapidly expanding prodn. and commercialization of CNTs and CNT-contg. materials in recent years, have raised concerns on the health risk of CNT exposure in humans. The CNT-induced pulmonary fibrotic lesions resemble those of human fibrotic lung diseases, such as idiopathic pulmonary fibrosis and pneumoconiosis, to a certain extent with regard to disease development and pathol. features. In fibrotic scenarios, immune cells are activated including varying immune pathways, ranging from innate immune cell activation to autoimmune disease. These events often precede and/or accompany the occurrence of fibrosis. Upon CNT exposure, significant induction and activation of Th2 cells and type 2 cytokines in the lungs are obsd. Moreover, type 2 pathways are shown to play important roles in promoting CNT-induced lung fibrosis by producing type 2 pro-fibrotic factors and inducing the reparative phenotypes of macrophages in response to CNTs. In light of the vastly increased demand for nanosafety and the apparent induction and multiple roles of type 2 immune pathways in lung fibrosis, we review the current literature on CNT-induced lung fibrosis, with a focus on the induction and activation of type 2 responses by CNTs and the stimulating function of type 2 signaling on pulmonary fibrosis development. These analyses provide new insights into the mechanistic understanding of CNT-induced lung fibrosis, as well as the potential of using type 2 responses as a monitoring target and therapeutic strategy for human fibrotic lung disease.
- 14Kasai, T.; Umeda, Y.; Ohnishi, M.; Mine, T.; Kondo, H.; Takeuchi, T.; Matsumoto, M.; Fukushima, S. Lung Carcinogenicity of Inhaled Multi-Walled Carbon Nanotube in Rats. Part. Fibre Toxicol. 2015, 13 (1), 53, DOI: 10.1186/s12989-016-0164-2Google ScholarThere is no corresponding record for this reference.
- 15Sakamoto, Y.; Hojo, M.; Kosugi, Y.; Watanabe, K.; Hirose, A.; Inomata, A.; Suzuki, T.; Nakae, D. Comparative Study for Carcinogenicity of 7 Different Multi-Wall Carbon Nanotubes with Different Physicochemical Characteristics by a Single Intraperitoneal Injection in Male Fischer 344 Rats. J. Toxicol. Sci. 2018, 43 (10), 587– 600, DOI: 10.2131/jts.43.587Google Scholar15https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXhtlOnu77K&md5=1833680dbebee46138d6d1a3d2f39fc2Comparative study for carcinogenicity of 7 different multi-wall carbon nanotubes with different physicochemical characteristics by a single intraperitoneal injection in male Fischer 344 ratsSakamoto, Yoshimitsu; Hojo, Motoki; Kosugi, Yuki; Watanabe, Kimiyo; Hirose, Akihiko; Inomata, Akiko; Suzuki, Toshinari; Nakae, DaiJournal of Toxicological Sciences (2018), 43 (10), 587-600CODEN: JTSCDR; ISSN:0388-1350. (Japanese Society of Toxicology)The present study comparatively examd. carcinogenicity of 7 different multi-wall carbon nanotubes (MWCNTs) with different physicochem. characteristics. Physicochem. characteristics of MWCNTs (referred to as M-, N-, WL-, SD1-, WS-, SD2- and T-CNTs in the present study) were detd. using scanning electron and light microscopes and a collision type inductively coupled plasma mass spectrometer. Male Fischer 344 rats (10 wk old, 15 animals per group) were administered MWCNTs at a single i.p. dose of 1 mg/kg body wt., and sacrificed up to 52 wk after the commencement. Fibers of M-, N-, WL- and SD1-CNTs were straight and acicular in shape, and contained few agglomerates. They were relatively long (38-59% of fibers were longer than 5μm) and thick (33% to more than 70% of fibers were thicker than 60 nm). Fibers of WS-, SD2- and T-CNTs were curled and tightly tangled to form frequent agglomerates. They were relatively short and thin (more than 90% of measured fibers were thinner than 50 nm). WS- CNT did not induce mesothelioma, and only one of 15 rat given SD2- or T-CNT developed tumor. Any correlations existed between the metal content and neither the size or form of fibers, nor the carcinogenicity. The straight and acicular shape without frequent agglomerates, and the relatively long and thick size, but not the iron content, may be crit. factors. The present data can contribute to the risk management, practical use and social acceptance of MWCNTs.
- 16Kodali, V.; Roberts, J. R.; Glassford, E.; Gill, R.; Friend, S.; Dunn, K. L.; Erdely, A. Understanding Toxicity Associated with Boron Nitride Nanotubes: Review of Toxicity Studies, Exposure Assessment at Manufacturing Facilities, and Read-Across. J. Mater. Res. 2022, 37, 4620– 4638, DOI: 10.1557/s43578-022-00796-8Google Scholar16https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB38Xisl2qtbzI&md5=12a33f72c50013a8870051bcb350f10fUnderstanding toxicity associated with boron nitride nanotubes: Review of toxicity studies, exposure assessment at manufacturing facilities, and read-acrossKodali, Vamsi; Roberts, Jenny R.; Glassford, Eric; Gill, Ryan; Friend, Sherri; Dunn, Kevin L.; Erdely, AaronJournal of Materials Research (2022), 37 (24), 4620-4638CODEN: JMREEE; ISSN:2044-5326. (Springer International Publishing AG)A review. Boron nitride nanotubes (BNNT) are produced by many different methods leading to variances in physicochem. characteristics and impurities in the final product. These differences can alter the toxicity profile. The importance of understanding the potential pathol. implications of this high aspect ratio nanomaterial is increasing as new approaches to synthesize and purify in large scale are being developed. In this review, we discuss the various factors of BNNT prodn. that can influence its toxicity followed by summarizing the toxicity findings from in vitro and in vivo studies conducted to date, including a review of particle clearance obsd. with various exposure routes. To understand the risk to workers and interpret relevance of toxicol. findings, exposure assessment at manufg. facilities was discussed. Workplace exposure assessment of BNNT from two manufg. facilities measured boron concns. in personal breathing zones from non-detectable to 0.95μg/m3 and TEM structure counts of 0.0123 ± 0.0094 structures/cm3, concns. well below what was found with other engineered high aspect ratio nanomaterials like carbon nanotubes and nanofibers. Finally, using a purified BNNT, a "read-across" toxicity assessment was performed to demonstrate how known hazard data and physicochem. characteristics can be utilized to evaluate potential inhalation toxicity concerns.
- 17Lucherelli, M. A.; Qian, X.; Weston, P.; Eredia, M.; Zhu, W.; Samorì, P.; Gao, H.; Bianco, A.; von dem Bussche, A. Boron Nitride Nanosheets Can Induce Water Channels Across Lipid Bilayers Leading to Lysosomal Permeabilization. Adv. Mater. 2021, 33 (45), 2103137, DOI: 10.1002/adma.202103137Google Scholar17https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3MXitFans7%252FJ&md5=0d4512d28ba902bffaddbe8705739229Boron Nitride Nanosheets Can Induce Water Channels Across Lipid Bilayers Leading to Lysosomal PermeabilizationLucherelli, Matteo Andrea; Qian, Xuliang; Weston, Paula; Eredia, Matilde; Zhu, Wenpeng; Samori, Paolo; Gao, Huajian; Bianco, Alberto; von dem Bussche, AnnetteAdvanced Materials (Weinheim, Germany) (2021), 33 (45), 2103137CODEN: ADVMEW; ISSN:0935-9648. (Wiley-VCH Verlag GmbH & Co. KGaA)While the interaction between 2D materials and cells is of key importance to the development of nanomedicines and safe applications of nanotechnol., still little is known about the biol. interactions of many emerging 2D materials. Here, an investigation of how hexagonal boron nitride (hBN) interacts with the cell membrane is carried out by combining mol. dynamics (MD), liq.-phase exfoliation, and in vitro imaging methods. MD simulations reveal that a sharp hBN wedge can penetrate a lipid bilayer and form a cross-membrane water channel along its exposed polar edges, while a round hBN sheet does not exhibit this behavior. It is hypothesized that such water channels can facilitate cross-membrane transport, with important consequences including lysosomal membrane permeabilization, an emerging mechanism of cellular toxicity that involves the release of cathepsin B and generation of radical oxygen species leading to cell apoptosis. To test this hypothesis, two types of hBN nanosheets, one with a rhomboidal, cornered morphol. and one with a round morphol., are prepd., and human lung epithelial cells are exposed to both materials. The cornered hBN with lateral polar edges results in a dose-dependent cytotoxic effect, whereas round hBN does not cause significant toxicity, thus confirming our premise.
- 18Kodali, V.; Kim, K. S.; Roberts, J. R.; Bowers, L.; Wolfarth, M. G.; Hubczak, J.; Xin, X.; Eye, T.; Friend, S.; Stefaniak, A. B. Influence of Impurities from Manufacturing Process on the Toxicity Profile of Boron Nitride Nanotubes. Small 2022, 18 (52), 2203259, DOI: 10.1002/smll.202203259Google Scholar18https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB38XivFSit7rI&md5=b716e0226709b9e83003e7bd39b90984Influence of Impurities from Manufacturing Process on the Toxicity Profile of Boron Nitride NanotubesKodali, Vamsi; Kim, Keun Su; Roberts, Jenny R.; Bowers, Lauren; Wolfarth, Michael G.; Hubczak, John; Xin, Xing; Eye, Tracy; Friend, Sherri; Stefaniak, Aleksandr B.; Leonard, Stephen S.; Jakubinek, Michael; Erdely, AaronSmall (2022), 18 (52), 2203259CODEN: SMALBC; ISSN:1613-6810. (Wiley-VCH Verlag GmbH & Co. KGaA)The toxicity of boron nitride nanotubes (BNNTs) has been the subject of conflicting reports, likely due to differences in the residuals and impurities that can make up to 30-60% of the material produced based on the manufg. processes and purifn. employed. Four BNNTs manufd. by induction thermal plasma process with a gradient of BNNT purity levels achieved through sequential gas purifn., water and solvent washing, allowed assessing the influence of these residuals/impurities on the toxicity profile of BNNTs. Extensive characterization including IR and X-ray spectroscopy, thermogravimetric anal., size, charge, surface area, and d. captured the alteration in physicochem. properties as the material went through sequential purifn. The material from each step is screened using acellular and in vitro assays for evaluating general toxicity, mechanisms of toxicity, and macrophage function. As the material increased in purity, there are more high-aspect-ratio particulates and a corresponding distinct increase in cytotoxicity, nuclear factor-κB transcription, and inflammasome activation. There is no alteration in macrophage function after BNNT exposure with all purity grades. The cytotoxicity and mechanism of screening clustered with the purity grade of BNNTs, illustrating that greater purity of BNNT corresponds to greater toxicity.
- 19Donaldson, K.; Murphy, F. A.; Duffin, R.; Poland, C. A. Asbestos, Carbon Nanotubes and the Pleural Mesothelium: A Review of the Hypothesis Regarding the Role of Long Fibre Retention in the Parietal Pleura, Inflammation and Mesothelioma. Part. Fibre Toxicol. 2010, 7, 5, DOI: 10.1186/1743-8977-7-5Google Scholar19https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC3c3nsF2jtg%253D%253D&md5=49db73fee80b155964e544fd639835b8Asbestos, carbon nanotubes and the pleural mesothelium: a review of the hypothesis regarding the role of long fibre retention in the parietal pleura, inflammation and mesotheliomaDonaldson Ken; Murphy Fiona A; Duffin Rodger; Poland Craig AParticle and fibre toxicology (2010), 7 (), 5 ISSN:.The unique hazard posed to the pleural mesothelium by asbestos has engendered concern in potential for a similar risk from high aspect ratio nanoparticles (HARN) such as carbon nanotubes. In the course of studying the potential impact of HARN on the pleura we have utilised the existing hypothesis regarding the role of the parietal pleura in the response to long fibres. This review seeks to synthesise our new data with multi-walled carbon nanotubes (CNT) with that hypothesis for the behaviour of long fibres in the lung and their retention in the parietal pleura leading to the initiation of inflammation and pleural pathology such as mesothelioma. We describe evidence that a fraction of all deposited particles reach the pleura and that a mechanism of particle clearance from the pleura exits, through stomata in the parietal pleura. We suggest that these stomata are the site of retention of long fibres which cannot negotiate them leading to inflammation and pleural pathology including mesothelioma. We cite thoracoscopic data to support the contention, as would be anticipated from the preceding, that the parietal pleura is the site of origin of pleural mesothelioma. This mechanism, if it finds support, has important implications for future research into the mesothelioma hazard from HARN and also for our current view of the origins of asbestos-initiated pleural mesothelioma and the common use of lung parenchymal asbestos fibre burden as a correlate of this tumour, which actually arises in the parietal pleura.
- 20Donaldson, K.; Murphy, F.; Schinwald, A.; Duffin, R.; Poland, C. A. Identifying the Pulmonary Hazard of High Aspect Ratio Nanoparticles to Enable Their Safety-by-Design. Nanomedicine 2011, 6 (1), 143– 156, DOI: 10.2217/nnm.10.139Google Scholar20https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3cXhs1WntbbO&md5=2bd96d8dc669b6d2f6be2fbc0000978fIdentifying the pulmonary hazard of high aspect ratio nanoparticles to enable their safety-by-designDonaldson, Ken; Murphy, Fiona; Schinwald, Anja; Duffin, Rodger; Poland, Craig A.Nanomedicine (London, United Kingdom) (2011), 6 (1), 143-156CODEN: NLUKAC; ISSN:1743-5889. (Future Medicine Ltd.)A review. High aspect ratio, or fiber-shaped, nanoparticles (HARNs) represent a growth area in nanotechnol. as their useful properties become more apparent. Carbon nanotubes, the best known and studied of the HARNs are handled on an increasingly large scale, with subsequent potential for human inhalation exposure. Their resemblance to asbestos fibers pptd. fears that they might show the same type of pathol. as that caused by asbestos and there is emerging evidence to support this possibility. The large no. of other HARNs, including nanorods, nanowires and other nanofibers, require similar toxicol. scrutiny. In this article we describe the unusual hazard assocd. with fibers, with special ref. to asbestos, and address the features of fibers that dictate their pathogenicity as developed in the fiber pathogenicity paradigm. This paradigm is a robust structure:toxicity model that identifies thin, long, biopersistent fibers as the ED for fiber-type pathogenic effects. It is likely that HARNs will in general conform to the paradigm and such an understanding of the features that make fibers pathogenic should enable us to design safer HARNs.
- 21Murphy, F.; Jacobsen, N. R.; Di Ianni, E.; Johnston, H.; Braakhuis, H.; Peijnenburg, W.; Oomen, A.; Fernandes, T.; Stone, V. Grouping MWCNTs Based on Their Similar Potential to Cause Pulmonary Hazard after Inhalation: A Case-Study. Part. Fibre Toxicol. 2022, 19 (1), 50, DOI: 10.1186/s12989-022-00487-6Google Scholar21https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BB2MbgsVGrug%253D%253D&md5=0e563f91bff4793fa9590da60ba3344aGrouping MWCNTs based on their similar potential to cause pulmonary hazard after inhalation: a case-studyMurphy Fiona; Johnston Helinor; Fernandes Teresa; Stone Vicki; Jacobsen Nicklas Raun; Di Ianni Emilio; Braakhuis Hedwig; Peijnenburg Willie; Oomen Agnes; Peijnenburg WillieParticle and fibre toxicology (2022), 19 (1), 50 ISSN:.BACKGROUND: The EU-project GRACIOUS developed an Integrated Approach to Testing and Assessment (IATA) to support grouping high aspect ratio nanomaterials (HARNs) presenting a similar inhalation hazard. Application of grouping reduces the need to assess toxicity on a case-by-case basis and supports read-across of hazard data from substances that have the data required for risk assessment (source) to those that lack such data (target). The HARN IATA, based on the fibre paradigm for pathogenic fibres, facilitates structured data gathering to propose groups of similar HARN and to support read-across by prompting users to address relevant questions regarding HARN morphology, biopersistence and inflammatory potential. The IATA is structured in tiers, allowing grouping decisions to be made using simple in vitro or in silico methods in Tier1 progressing to in vivo approaches at the highest Tier3. Here we present a case-study testing the applicability of GRACIOUS IATA to form an evidence-based group of multiwalled carbon nanotubes (MWCNT) posing a similar predicted fibre-hazard, to support read-across and reduce the burden of toxicity testing. RESULTS: The case-study uses data on 15 different MWCNT, obtained from the published literature. By following the IATA, a group of 2 MWCNT was identified (NRCWE006 and NM-401) based on a high degree of similarity. A pairwise similarity assessment was subsequently conducted between the grouped MWCNT to evaluate the potential to conduct read-across and fill data gaps required for regulatory hazard assessment. The similarity assessment, based on expert judgement of Tier 1 assay results, predicts both MWCNT are likely to cause a similar acute in vivo hazard. This result supports the possibility for read-across of sub-chronic and chronic hazard endpoint data for lung fibrosis and carcinogenicity between the 2 grouped MWCNT. The implications of accepting the similarity assessment based on expert judgement of the MWCNT group are considered to stimulate future discussion on the level of similarity between group members considered sufficient to allow regulatory acceptance of a read-across argument. CONCLUSION: This proof-of-concept case-study demonstrates how a grouping hypothesis and IATA may be used to support a nuanced and evidence-based grouping of 'similar' MWCNT and the subsequent interpolation of data between group members to streamline the hazard assessment process.
- 22Murphy, F.; Dekkers, S.; Braakhuis, H.; Ma-Hock, L.; Johnston, H.; Janer, G.; di Cristo, L.; Sabella, S.; Jacobsen, N. R.; Oomen, A. G. An Integrated Approach to Testing and Assessment of High Aspect Ratio Nanomaterials and Its Application for Grouping Based on a Common Mesothelioma Hazard. NanoImpact 2021, 22, 100314, DOI: 10.1016/j.impact.2021.100314Google Scholar22https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB38XhtlSrsL%252FE&md5=0faa3b8f71ca2d66f3f101c659882507An integrated approach to testing and assessment of high aspect ratio nanomaterials and its application for grouping based on a common mesothelioma hazardMurphy, Fiona; Dekkers, Susan; Braakhuis, Hedwig; Ma-Hock, Lan; Johnston, Helinor; Janer, Gemma; di Cristo, Luisana; Sabella, Stefania; Jacobsen, Nicklas Raun; Oomen, Agnes G.; Haase, Andrea; Fernandes, Teresa; Stone, VickiNanoImpact (2021), 22 (), 100314CODEN: NANOPT; ISSN:2452-0748. (Elsevier B.V.)Here we describe the development of an Integrated Approach to Testing and Assessment (IATA) to support the grouping of different types (nanoforms; NFs) of High Aspect Ratio Nanomaterials (HARNs), based on their potential to cause mesothelioma. Hazards posed by the inhalation of HARNs are of particular concern as they exhibit phys. characteristics similar to pathogenic asbestos fibers. The approach for grouping HARNs presented here is part of a framework to provide guidance and tools to group similar NFs and aims to reduce the need to assess toxicity on a case-by-case basis. The approach to grouping is hypothesis-driven, in which the hypothesis is based on scientific evidence linking crit. physicochem. descriptors for NFs to defined fate/toxicokinetic and hazard outcomes. The HARN IATA prompts users to address relevant questions (at decision nodes; DNs) regarding the morphol., biopersistence and inflammatory potential of the HARNs under investigation to provide the necessary evidence to accept or reject the grouping hypothesis. Each DN in the IATA is addressed in a tiered manner, using data from simple in vitro or in silico methods in the lowest tier or from in vivo approaches in the highest tier. For these proposed methods we provide justification for the crit. descriptors and thresholds that allow grouping decisions to be made. Application of the IATA allows the user to selectively identify HARNs which may pose a mesothelioma hazard, as demonstrated through a literature-based case study. By promoting the use of alternative, non-rodent approaches such as in silico modeling, in vitro and cell-free tests in the initial tiers, the IATA testing strategy streamlines information gathering at all stages of innovation through to regulatory risk assessment while reducing the ethical, time and economic burden of testing.
- 23Nel, A. Carbon Nanotube Pathogenicity Conforms to a Unified Theory for Mesothelioma Causation by Elongate Materials and Fibers. Environ. Res. 2023, 230, 114580 DOI: 10.1016/j.envres.2022.114580Google Scholar23https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3sXmtVSjtbY%253D&md5=fcaba6897bffb8375fa6dff3e3a2bde7Carbon nanotube pathogenicity conforms to a unified theory for mesothelioma causation by elongate materials and fibersNel, AndreEnvironmental Research (2023), 230 (), 114580CODEN: ENVRAL; ISSN:0013-9351. (Elsevier Inc.)A review. The purpose of this review is to elucidate how dimensional and durability characteristics of high aspect ratio nanomaterials (HARN), including carbon nanotubes (CNT) and metal nanowires (MeNW), contribute to understanding the fiber pathogenicity paradigm (FPP), including by explaining the structure-activity relationships (SAR) of a diverse range of natural and synthetic elongate materials that may or may not contribute to mesothelioma development in the lung. While the FPP was originally developed to explain the crit. importance of asbestos and synthetic vitreous fiber length, width, aspect ratio and biopersistence in mesothelioma development, there are a vast no. of addnl. inhalable materials that need to be considered in terms of pathogenic features that may contribute to mesothelioma or lack thereof. Not only does the ability to exert more exact control over the length and biopersistence of HARNs confirm the tenets of the FPP, but could be studied by implementating more appropriate toxicol. tools for SAR anal. This includes experimentation with carefully assembled libraries of CNTs and MeNWs, helping to establish more precise dimensional features for interfering in lymphatic drainage from the parietal pleura, triggering of lysosomal damage, frustrated phagocytosis and generation of chronic inflammation. The evidence includes data that long and rigid, but not short and flexible multi-wall CNTs are capable of generating mesotheliomas in rodents based on an adverse outcome pathway requiring access to pleural cavity, obstruction of pleural stomata, chronic inflammation and transformation of mesothelial cells. In addn. to durability and dimensional characteristics, bending stiffness of CNTs is a crit. factor in detg. the shape and rigidity of pathogenic MWCNTs. While no evidence has been obtained in humans that CNT exposure leads to a mesothelioma outcome, it is important to monitor exposure levels and health effect impacts in workers to prevent adverse health outcomes in humans.
- 24Rodrigues, A. F.; Newman, L.; Jasim, D. A.; Vacchi, I. A.; Ménard-Moyon, C.; Crica, L. E.; Bianco, A.; Kostarelos, K.; Bussy, C. Immunological Impact of Graphene Oxide Sheets in the Abdominal Cavity Is Governed by Surface Reactivity. Arch. Toxicol. 2018, 92 (11), 3359– 3379, DOI: 10.1007/s00204-018-2303-zGoogle Scholar24https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1cXhvVSmsL%252FL&md5=e47ab5e6e62bd31b8e8e64fd9fd7c909Immunological impact of graphene oxide sheets in the abdominal cavity is governed by surface reactivityRodrigues, Artur Filipe; Newman, Leon; Jasim, Dhifaf A.; Vacchi, Isabella A.; Menard-Moyon, Cecilia; Crica, Livia E.; Bianco, Alberto; Kostarelos, Kostas; Bussy, CyrillArchives of Toxicology (2018), 92 (11), 3359-3379CODEN: ARTODN; ISSN:0340-5761. (Springer)Graphene oxide (GO) is an oxidised form of graphene that has attracted com. interest in multiple applications, including inks, printed electronics and spray coatings, which all raise health concerns due to potential creation of inhalable aerosols. Although a no. of studies have discussed the toxicity of GO sheets, the in vivo impact of their lateral dimensions is still not clear. To benchmark the outcomes, long and rigid multi-walled carbon nanotubes (MWCNTs) that were shown to be assocd. with asbestos-like pathogenicity on the mesothelium were also tested. Our aim was to assess whether lateral dimensions can be a predictor of inflammogenicity for GO sheets in a similar fashion as length is for MWCNTs. Such recruitment coincided with the greater ability of s-GO to interact in vivo with peritoneal macrophages and was assocd. with a greater surface reactivity in comparison to l-GO. In conclusion, large dimension was not a detg. factor of the immunol. impact of GO sheets after i.p. administration. On the other hand, surface reactivity and the ability of some smaller GO sheets to interact more readily with immune cells seem to be key parameters that can be tuned to improve the safety profile of GO. Overall, these findings are essential for a better understanding of the parameters governing GO toxicity and inflammation, and the rational design of safe GO-based formulations for various applications, including biomedicine.
- 25Rodrigues, A. F.; Newman, L.; Jasim, D.; Mukherjee, S. P.; Wang, J.; Vacchi, I. A.; Ménard-Moyon, C.; Bianco, A.; Fadeel, B.; Kostarelos, K. Size-Dependent Pulmonary Impact of Thin Graphene Oxide Sheets in Mice: Toward Safe-by-Design. Adv. Sci. 2020, 7 (12), 1903200 DOI: 10.1002/advs.201903200Google Scholar25https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXitVKhtbvK&md5=f16648d20bb53e8b539e8cca382ec6d2Size-Dependent Pulmonary Impact of Thin Graphene Oxide Sheets in Mice: Toward Safe-by-DesignRodrigues, Artur Filipe; Newman, Leon; Jasim, Dhifaf; Mukherjee, Sourav P.; Wang, Jun; Vacchi, Isabella A.; Menard-Moyon, Cecilia; Bianco, Alberto; Fadeel, Bengt; Kostarelos, Kostas; Bussy, CyrillAdvanced Science (Weinheim, Germany) (2020), 7 (12), 1903200CODEN: ASDCCF; ISSN:2198-3844. (Wiley-VCH Verlag GmbH & Co. KGaA)Safety assessment of graphene-based materials (GBMs) including graphene oxide (GO) is essential for their safe use across many sectors of society. In particular, the link between specific material properties and biol. effects needs to be further elucidated. Here, the effects of lateral dimensions of GO sheets in acute and chronic pulmonary responses after single intranasal instillation in mice are compared. Micrometer-sized GO induces stronger pulmonary inflammation than nanometer-sized GO, despite reduced translocation to the lungs. Genome-wide RNA sequencing also reveals distinct size-dependent effects of GO, in agreement with the histopathol. results. Although large GO, but not the smallest GO, triggers the formation of granulomas that persists for up to 90 days, no pulmonary fibrosis is obsd. These latter results can be partly explained by Raman imaging, which evidences the progressive biotransformation of GO into less graphitic structures. The findings demonstrate that lateral dimensions play a fundamental role in the pulmonary response to GO, and suggest that airborne exposure to micrometer-sized GO should be avoided in the prodn. plant or applications, where aerosolized dispersions are likely to occur. These results are important toward the implementation of a safer-by-design approach for GBM products and applications, for the benefit of workers and end-users.
- 26Loret, T.; Visani de Luna, L. A.; Fordham, A.; Arshad, A.; Barr, K.; Lozano, N.; Kostarelos, K.; Bussy, C. Innate but Not Adaptive Immunity Regulates Lung Recovery from Chronic Exposure to Graphene Oxide Nanosheets. Adv. Sci. 2022, 9, 2104559 DOI: 10.1002/advs.202104559Google Scholar26https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB38XhtVGis7jJ&md5=0e6623de2252bce8609db83148e7547aInnate but Not Adaptive Immunity Regulates Lung Recovery from Chronic Exposure to Graphene Oxide NanosheetsLoret, Thomas; de Luna, Luis Augusto Visani; Fordham, Alexander; Arshad, Atta; Barr, Katharine; Lozano, Neus; Kostarelos, Kostas; Bussy, CyrillAdvanced Science (Weinheim, Germany) (2022), 9 (11), 2104559CODEN: ASDCCF; ISSN:2198-3844. (Wiley-VCH Verlag GmbH & Co. KGaA)Graphene has drawn a lot of interest in the material community due to unique physicochem. properties. Owing to a high surface area to vol. ratio and free oxygen groups, the oxidized deriv., graphene oxide (GO) has promising potential as a drug delivery system. Here, the lung tolerability of two distinct GO varying in lateral dimensions is investigated, to reveal the most suitable candidate platform for pulmonary drug delivery. Following repeated chronic pulmonary exposure of mice to GO sheet suspensions, the innate and adaptive immune responses are studied. An acute and transient influx of neutrophils and eosinophils in the alveolar space, together with the replacement of alveolar macrophages by interstitial ones and a significant activation toward anti-inflammatory subsets, are found for both GO materials. Micrometric GO give rise to persistent multinucleated macrophages and granulomas. However, neither adaptive immune response nor lung tissue remodeling are induced after exposure to micrometric GO. Concurrently, milder effects and faster tissue recovery, both assocd. to a faster clearance from the respiratory tract, are found for nanometric GO, suggesting a greater lung tolerability. Taken together, these results highlight the importance of dimensions in the design of biocompatible 2D materials for pulmonary drug delivery system.
- 27Visani de Luna, L. A.; Loret, T.; Fordham, A.; Arshad, A.; Drummond, M.; Dodd, A.; Lozano, N.; Kostarelos, K.; Bussy, C. Lung Recovery from DNA Damage Induced by Graphene Oxide Is Dependent on Size, Dose and Inflammation Profile. Part. Fibre Toxicol. 2022, 19, 62, DOI: 10.1186/s12989-022-00502-wGoogle ScholarThere is no corresponding record for this reference.
- 28Smith, R. J.; King, P. J.; Lotya, M.; Wirtz, C.; Khan, U.; De, S.; O’Neill, A.; Duesberg, G. S.; Grunlan, J. C.; Moriarty, G. Large-Scale Exfoliation of Inorganic Layered Compounds in Aqueous Surfactant Solutions. Adv. Mater. 2011, 23 (34), 3944– 3948, DOI: 10.1002/adma.201102584Google Scholar28https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXpsFaisrg%253D&md5=ad837ed3dce21542d32ba74b7410603aLarge-Scale Exfoliation of Inorganic Layered Compounds in Aqueous Surfactant SolutionsSmith, Ronan J.; King, Paul J.; Lotya, Mustafa; Wirtz, Christian; Khan, Umar; De, Sukanta; O'Neill, Arlene; Duesberg, Georg S.; Grunlan, Jaime C.; Moriarty, Gregory; Chen, Jun; Wang, Jiazhao; Minett, Andrew I.; Nicolosi, Valeria; Coleman, Jonathan N.Advanced Materials (Weinheim, Germany) (2011), 23 (34), 3944-3948CODEN: ADVMEW; ISSN:0935-9648. (Wiley-VCH Verlag GmbH & Co. KGaA)We show a simple, large-scale method to exfoliate layered compds. such as BN, transition metal dichalcogenides, and transition metal oxides down to very thin platelets in water. The platelets are stabilized against reaggregation by a surfactant coating. This method is robust, can be carried out in ambient conditions, is scalable, and allows the prepn. of films, hybrids, and composites. We suggest that ionic surfactants are ideal stabilizers due to their van der Waals binding to the exfoliated nanosheets and subsequent electrostatic stabilization.
- 29Lago, E.; Toth, P. S.; Gentiluomo, S.; Thorat, S. B.; Pellegrini, V.; Bonaccorso, F. Dependence of the Polycarbonate Mechanical Performances on Boron Nitride Flakes Morphology. JPhys. Mater. 2021, 4 (4). 045002 DOI: 10.1088/2515-7639/ac0ac0 .Google Scholar29https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3MXislehsbzJ&md5=dff95ae94fee6d51d8b3be818e78f3cfDependence of the polycarbonate mechanical performances on boron nitride flakes morphologyLago, Emanuele; Toth, Peter S.; Gentiluomo, Silvia; Thorat, Sanjay B.; Pellegrini, Vittorio; Bonaccorso, FrancescoJPhys Materials (2021), 4 (4), 045002CODEN: JPMOC4; ISSN:2515-7639. (IOP Publishing Ltd.)A key requirement for the exploitation of two-dimensional (2D)-crystals in the field of composites relies on their large-scale prodn. In this respect, liq. phase exfoliation of layered-crystals is emerging as one of the most promising approaches for the scalable prodn. of high-quality 2D-crystals. However, the dependence of the 2D crystal flakes morphol., i.e. thickness and lateral size, on the mech. properties of the polymer composites is not fully understood yet. Herein, we tackle this issue by designing an environmentally friendly approach, based on the exfoliation of bulk hexagonal-boron nitride (h-BN), widely used as filler in polymer composites for its high intrinsic stiffness, i.e. approaching 1 TPa, in a water/surfactant soln. with controlled thickness and lateral size by using cascade ultra-centrifugation. Our approach allows us to obtain two populations of flakes with aspect ratio, i.e. lateral size over thickness, equal to 250 and 350, resp. The h-BN flakes with tuned aspect ratio are subsequently used as filler in a polycarbonate (PC) matrix by exploiting soln. blending in 1,3-dioxolane, a solvent with Hansen's soly. parameters matching the ones of h-BN, thus enhancing the dispersion of the filler inside the matrix, as evaluated by Raman mapping. We tested the composite mech. properties finding that flakes with higher aspect ratio show superior reinforcements in terms of both ultimate tensile strength and Young's modulus, compared with their lower aspect ratio counterparts. As example, at 0.1 wt% of loading, the difference in reinforcement in terms of Young's Modulus is of 56 MPa, being the increment, compared to pristine PC, of ~ 22% for composites produced with higher aspect ratio fillers, whereas it is instead of only ~ 17% for lower aspect ratio fillers.
- 30Huang, C.; Chen, C.; Ye, X.; Ye, W.; Hu, J.; Xu, C.; Qiu, X. Stable Colloidal Boron Nitride Nanosheet Dispersion and Its Potential Application in Catalysis. J. Mater. Chem. A 2013, 1 (39). 12192 DOI: 10.1039/c3ta12231j .Google Scholar30https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXhsVOgsL3I&md5=ddf40d62e4ca44c80bca0991c2ecfe45Stable colloidal boron nitride nanosheet dispersion and its potential application in catalysisHuang, Caijin; Chen, Cheng; Ye, Xinxin; Ye, Weiqing; Hu, Jinli; Xu, Chao; Qiu, XiaoqingJournal of Materials Chemistry A: Materials for Energy and Sustainability (2013), 1 (39), 12192-12197CODEN: JMCAET; ISSN:2050-7496. (Royal Society of Chemistry)Stable colloidal nanosheet dispersions of hexagonal boron nitride (h-BN) with high concn. have been prepd. in ethylene glycol using matching of the surface energies of h-BN and the surface tension of the solvent. Bulk h-BN was directly exfoliated and dispersed in ethylene glycol with the assistance of sonication to form stable h-BN nanosheets with a few layers. The stable colloidal h-BN nanosheets were good carriers to support and disperse noble metal nanoparticles such as Ag, Au, and Pt with high catalytic activity for the redn. of p-nitrophenol.
- 31Si, P. Z.; Zhang, M.; You, C. Y.; Geng, D. Y.; Du, J. H.; Zhao, X. G.; Ma, X. L.; Zhang, Z. D. Amorphous Boron Nanoparticles and BN Encapsulating Boron Nano-Peanuts Prepared by Arc-Decomposing Diborane and Nitriding. J. Mater. Sci. 2003, 38 (4), 689– 692, DOI: 10.1023/A:1021832209250Google Scholar31https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD3sXit1GjsQ%253D%253D&md5=4a5526db33c7eff92012cb05fcf3ec9bAmorphous boron nanoparticles and BN encapsulating boron nano-peanuts prepared by arc-decomposing diborane and nitridingSi, P. Z.; Zhang, M.; You, C. Y.; Geng, D. Y.; Du, J. H.; Zhao, X. G.; Ma, X. L.; Zhang, Z. D.Journal of Materials Science (2003), 38 (4), 689-692CODEN: JMTSAS; ISSN:0022-2461. (Kluwer Academic Publishers)Amorphous boron nanoparticles were prepd. by arc-decompg. diborane, which had ideal morphologies in comparison with that of those fabricated by furnace or laser heating diborane. Peanut-shaped boron nitride encapsulating boron nanocapsules were fabricated by nitridation of amorphous boron nanoparticles. Unique core/void/shell structure of the nanocapsules was obsd. by a high-resoln. TEM. The mechanism of growing the BN nanocapsules by a catalyst-free process was distinctly different from the process of arc discharge or laser heating. The broadening of nonpolar intralayer Raman line of hexagonal BN at about 1370 cm-1 was obsd., which was attributed to the small crystal size of BN.
- 32Kurapati, R.; Backes, C.; Ménard-Moyon, C.; Coleman, J. N.; Bianco, A. White Graphene Undergoes Peroxidase Degradation. Angew. Chemie Int. Ed. 2016, 55 (18), 5506– 5511, DOI: 10.1002/anie.201601238Google Scholar32https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28XkvVChsb4%253D&md5=4cda956f69edbd641ef56712dd476255White Graphene undergoes Peroxidase DegradationKurapati, Rajendra; Backes, Claudia; Menard-Moyon, Cecilia; Coleman, Jonathan N.; Bianco, AlbertoAngewandte Chemie, International Edition (2016), 55 (18), 5506-5511CODEN: ACIEF5; ISSN:1433-7851. (Wiley-VCH Verlag GmbH & Co. KGaA)Hexagonal boron nitride (hBN) nanosheets are emerging as promising 2D materials for different types of applications. However, biodegrdn. of hBN materials is poorly explored owing to their high chem. inertness and strong oxidn. resistance. The assessment of oxidn./biodegrdn. of hBN is important in developing biomedical tools. Herein, we report the first study on the biodegradability of hBN nanosheets comparing the enzymic catalysis of two different peroxidases, horseradish peroxidase (HRP) and human myeloperoxidase (MPO), with the photo-Fenton (P.F.) reaction. The results show that degrdn. of hBN nanosheets is different to that of graphene and graphene oxide, since partial oxidn. was found using MPO after 35 h, while HRP failed to degrade hBN up to 60 days. Nearly complete oxidn./degrdn. was occurred by P. F. reaction in 100 h. These results are helpful in designing advanced conjugates for biomedical uses of hBN.
- 33Saber, A. T.; Jacobsen, N. R.; Jackson, P.; Poulsen, S. S.; Kyjovska, Z. O.; Halappanavar, S.; Yauk, C. L.; Wallin, H.; Vogel, U. Particle-Induced Pulmonary Acute Phase Response May Be the Causal Link between Particle Inhalation and Cardiovascular Disease. Wiley Interdisciplinary Reviews: Nanomedicine and Nanobiotechnology. 2014, 6, 517– 531, DOI: 10.1002/wnan.1279Google Scholar33https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXhslCqtrrJ&md5=539e8a0089973ad44ab30ebb9049cae5Particle-induced pulmonary acute phase response may be the causal link between particle inhalation and cardiovascular diseaseSaber, Anne T.; Jacobsen, Nicklas R.; Jackson, Petra; Poulsen, Sarah Sos; Kyjovska, Zdenka O.; Halappanavar, Sabina; Yauk, Carole L.; Wallin, Hakan; Vogel, UllaWiley Interdisciplinary Reviews: Nanomedicine and Nanobiotechnology (2014), 6 (6), 517-531CODEN: WIRNBH; ISSN:1939-0041. (Wiley-Blackwell)Inhalation of ambient and workplace particulate air pollution is assocd. with increased risk of cardiovascular disease. One proposed mechanism for this assocn. is that pulmonary inflammation induces a hepatic acute phase response, which increases risk of cardiovascular disease. Induction of the acute phase response is intimately linked to risk of cardiovascular disease as shown in both epidemiol. and animal studies. Indeed, blood levels of acute phase proteins, such as C-reactive protein and serum amyloid A, are independent predictors of risk of cardiovascular disease in prospective epidemiol. studies. In this review, we present and review emerging evidence that inhalation of particles (e.g., air diesel exhaust particles and nanoparticles) induces a pulmonary acute phase response, and propose that this induction constitutes the causal link between particle inhalation and risk of cardiovascular disease. Increased levels of acute phase mRNA and proteins in lung tissues, bronchoalveolar lavage fluid and plasma clearly indicate pulmonary acute phase response following pulmonary deposition of different kinds of particles including diesel exhaust particles, nanoparticles, and carbon nanotubes. The pulmonary acute phase response is dose-dependent and long lasting. Conversely, the hepatic acute phase response is reduced relative to lung or entirely absent. We also provide evidence that pulmonary inflammation, as measured by neutrophil influx, is a predictor of the acute phase response and that the total surface area of deposited particles correlates with the pulmonary acute phase response. We discuss the implications of these findings in relation to occupational exposure to nanoparticles.
- 34Hadrup, N.; Zhernovkov, V.; Jacobsen, N. R.; Voss, C.; Strunz, M.; Ansari, M.; Schiller, H. B.; Halappanavar, S.; Poulsen, S. S.; Kholodenko, B. Acute Phase Response as a Biological Mechanism-of-Action of (Nano)Particle-Induced Cardiovascular Disease. Small. 2020, DOI: 10.1002/smll.201907476Google ScholarThere is no corresponding record for this reference.
- 35Loret, T.; de Luna, L. A. V.; Lucherelli, M. A.; Fordham, A.; Lozano, N.; Bianco, A.; Kostarelos, K.; Bussy, C. Lung Persistence, Biodegradation, and Elimination of Graphene-Based Materials Are Predominantly Size-Dependent and Mediated by Alveolar Phagocytes. Small 2023, 19, 2301201 DOI: 10.1002/smll.202301201Google Scholar35https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3sXhtFGnur7O&md5=6b4e8ece4eabf5bf0be030ab4a840359Lung Persistence, Biodegradation, and Elimination of Graphene-Based Materials are Predominantly Size-Dependent and Mediated by Alveolar PhagocytesLoret, Thomas; de Luna, Luis Augusto Visani; Lucherelli, Matteo Andrea; Fordham, Alexander; Lozano, Neus; Bianco, Alberto; Kostarelos, Kostas; Bussy, CyrillSmall (2023), 19 (39), 2301201CODEN: SMALBC; ISSN:1613-6810. (Wiley-VCH Verlag GmbH & Co. KGaA)Graphene-based materials (GBMs) have promising applications in various sectors, including pulmonary nanomedicine. Nevertheless, the influence of GBM physicochem. characteristics on their fate and impact in lung has not been thoroughly addressed. To fill this gap, the biol. response, distribution, and bio-persistence of four different GBMs in mouse lungs up to 28 days after single oropharyngeal aspiration are investigated. None of the GBMs, varying in size (large vs. small) and carbon to oxygen ratio as well as thickness (few-layers graphene (FLG) vs. thin graphene oxide (GO)), induce a strong pulmonary immune response. However, recruited neutrophils internalize nanosheets better and degrade GBMs faster than macrophages, revealing their crucial role in the elimination of small GBMs. In contrast, large GO sheets induce more damages due to a hindered degrdn. and long-term persistence in macrophages. Overall, small dimensions appear to be a leading feature in the design of safe GBM pulmonary nanovectors due to an enhanced degrdn. in phagocytes and a faster clearance from the lungs for small GBMs. Thickness also plays an important role, since decreased material loading in alveolar phagocytes and faster elimination are found for FLGs compared to thinner GOs. These results are important for designing safer-by-design GBMs for biomedical application.
- 36Poland, C. A.; Duffin, R.; Kinloch, I. A.; Maynard, A.; Wallace, W. A. H.; Seaton, A.; Stone, V.; Brown, S.; Macnee, W.; Donaldson, K. Carbon Nanotubes Introduced into the Abdominal Cavity of Mice Show Asbestos-like Pathogenicity in a Pilot Study. Nat. Nanotechnol. 2008, 3 (7), 423– 428, DOI: 10.1038/nnano.2008.111Google Scholar36https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1cXotFehs7o%253D&md5=54ae8b1abbe311ade69bb8255891b407Carbon nanotubes introduced into the abdominal cavity of mice show asbestos-like pathogenicity in a pilot studyPoland, Craig A.; Duffin, Rodger; Kinloch, Ian; Maynard, Andrew; Wallace, William A. H.; Seaton, Anthony; Stone, Vicki; Brown, Simon; MacNee, William; Donaldson, KenNature Nanotechnology (2008), 3 (7), 423-428CODEN: NNAABX; ISSN:1748-3387. (Nature Publishing Group)Carbon nanotubes have distinctive characteristics, but their needle-like fiber shape has been compared to asbestos, raising concerns that widespread use of carbon nanotubes may lead to mesothelioma, cancer of the lining of the lungs caused by exposure to asbestos. Exposing the mesothelial lining of the body cavity of mice, as a surrogate for the mesothelial lining of the chest cavity, to long multiwalled carbon nanotubes results in asbestos-like, length-dependent, pathogenic behavior. This includes inflammation and the formation of lesions known as granulomas. This is of considerable importance, because research and business communities continue to invest heavily in carbon nanotubes for a wide range of products under the assumption that they are no more hazardous than graphite. The authors' results suggest the need for further research and great caution before introducing such products into the market if long-term harm is to be avoided. A pilot study in a small no. of mice shows that long multiwalled carbon nanotubes introduced into the abdominal cavity can cause asbestos-like pathogenic behavior. The results suggest the need for further research and caution before introducing nanotube products into the market.
- 37Christophersen, D. V.; Møller, P.; Thomsen, M. B.; Lykkesfeldt, J.; Loft, S.; Wallin, H.; Vogel, U.; Jacobsen, N. R. Accelerated Atherosclerosis Caused by Serum Amyloid A Response in Lungs of ApoE–/– Mice. FASEB J. 2021, 35 (3), e21307, DOI: 10.1096/fj.202002017RGoogle Scholar37https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3MXmt1elsLY%253D&md5=64a14843ddbceb90956c025b50131ba0Accelerated atherosclerosis caused by serum amyloid A response in lungs of ApoE-/- miceChristophersen, Daniel Vest; Moeller, Peter; Thomsen, Morten Baekgaard; Lykkesfeldt, Jens; Loft, Steffen; Wallin, Hakan; Vogel, Ulla; Jacobsen, Nicklas RaunFASEB Journal (2021), 35 (3), e21307CODEN: FAJOEC; ISSN:1530-6860. (John Wiley & Sons, Inc.)Airway exposure to eg particulate matter is assocd. with cardiovascular disease including atherosclerosis. Acute phase genes, esp. Serum Amyloid A3 (Saa3), are highly expressed in the lung following pulmonary exposure to particles. We aimed to investigate whether the human acute phase protein SAA (a homolog to mouse SAA3) accelerated atherosclerotic plaque progression in Apolipoprotein E knockout (ApoE-/-) mice. Mice were intratracheally (i.t.) instilled with vehicle (phosphate buffered saline) or 2μg human SAA once a week for 10 wk. Plaque progression was assessed in the aorta using noninvasive ultrasound imaging of the aorta arch as well as by en face anal. Addnl., lipid peroxidn., SAA3, and cholesterol were measured in plasma, inflammation was detd. in lung, and mRNA levels of the acute phase genes Saa1 and Saa3 were measured in the liver and lung, resp. Repeated i.t. instillation with SAA caused a significant progression in the atherosclerotic plaques in the aorta (1.5-fold). Concomitantly, SAA caused a statistically significant increase in neutrophils in bronchoalveolar lavage fluid (625-fold), in pulmonary Saa3 (196-fold), in systemic SAA3 (1.8-fold) and malondialdehyde levels (1.14-fold), indicating acute phase response (APR), inflammation and oxidative stress. Finally, pulmonary exposure to SAA significantly decreased the plasma levels of very low-d. lipoproteins - low-d. lipoproteins and total cholesterol, possibly due to lipids being sequestered in macrophages or foam cells in the arterial wall. Combined these results indicate the importance of the pulmonary APR and SAA3 for plaque progression.
- 38Gutierrez, C. T.; Loizides, C.; Hafez, I.; Brostrøm, A.; Wolff, H.; Szarek, J.; Berthing, T.; Mortensen, A.; Jensen, K. A.; Roursgaard, M. Acute Phase Response Following Pulmonary Exposure to Soluble and Insoluble Metal Oxide Nanomaterials in Mice. Part. Fibre Toxicol. 2023, 20 (1), 4, DOI: 10.1186/s12989-023-00514-0Google Scholar38https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3sXitFSmsrg%253D&md5=c2bf4e3a4d4094ca47d19efcffc63d31Acute phase response following pulmonary exposure to soluble and insoluble metal oxide nanomaterials in miceGutierrez, Claudia Torero; Loizides, Charis; Hafez, Iosif; Brostroem, Anders; Wolff, Henrik; Szarek, Jozef; Berthing, Trine; Mortensen, Alicja; Jensen, Keld Alstrup; Roursgaard, Martin; Saber, Anne Thoustrup; Moeller, Peter; Biskos, George; Vogel, UllaParticle and Fibre Toxicology (2023), 20 (1), 4CODEN: PFTABQ; ISSN:1743-8977. (BioMed Central Ltd.)Acute phase response (APR) is characterized by a change in concn. of different proteins, including C-reactive protein and serum amyloid A (SAA) that can be linked to both exposure to metal oxide nanomaterials and risk of cardiovascular diseases. In this study, we intratracheally exposed mice to ZnO, CuO, Al2O3, SnO2 and TiO2 and carbon black (Printex 90) nanomaterials with a wide range in phagolysosomal soly. We subsequently assessed neutrophil nos., protein and lactate dehydrogenase activity in bronchoalveolar lavage fluid, Saa3 and Saa1 mRNA levels in lung and liver tissue, resp., and SAA3 and SAA1/2 in plasma. Endpoints were analyzed 1 and 28 days after exposure, including histopathol. of lung and liver tissues. All nanomaterials induced pulmonary inflammation after 1 day, and exposure to ZnO, CuO, SnO2, TiO2 and Printex 90 increased Saa3 mRNA levels in lungs and Saa1 mRNA levels in liver. Addnl., CuO, SnO2, TiO2 and Printex 90 increased plasma levels of SAA3 and SAA1/2. Acute phase response was predicted by deposited surface area for insol. metal oxides, 1 and 28 days post-exposure. Sol. and insol. metal oxides induced dose-dependent APR with different time dependency. Neutrophil influx, Saa3 mRNA levels in lung tissue and plasma SAA3 levels correlated across all studied nanomaterials, suggesting that these endpoints can be used as biomarkers of acute phase response and cardiovascular disease risk following exposure to sol. and insol. particles.
- 39Fadeel, B.; Bussy, C.; Merino, S.; Vázquez, E.; Flahaut, E.; Mouchet, F.; Evariste, L.; Gauthier, L.; Koivisto, A. J.; Vogel, U. Safety Assessment of Graphene-Based Materials: Focus on Human Health and the Environment. ACS Nano 2018, 12 (11), 10582– 10620, DOI: 10.1021/acsnano.8b04758Google Scholar39https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1cXitVyju7nN&md5=f276495b7b3b777acedf279460618b25Safety Assessment of Graphene-Based Materials: Focus on Human Health and the EnvironmentFadeel, Bengt; Bussy, Cyrill; Merino, Sonia; Vazquez, Ester; Flahaut, Emmanuel; Mouchet, Florence; Evariste, Lauris; Gauthier, Laury; Koivisto, Antti J.; Vogel, Ulla; Martin, Cristina; Delogu, Lucia G.; Buerki-Thurnherr, Tina; Wick, Peter; Beloin-Saint-Pierre, Didier; Hischier, Roland; Pelin, Marco; Candotto Carniel, Fabio; Tretiach, Mauro; Cesca, Fabrizia; Benfenati, Fabio; Scaini, Denis; Ballerini, Laura; Kostarelos, Kostas; Prato, Maurizio; Bianco, AlbertoACS Nano (2018), 12 (11), 10582-10620CODEN: ANCAC3; ISSN:1936-0851. (American Chemical Society)A review. Graphene and its derivs. are heralded as "miracle" materials with manifold applications in different sectors of society from electronics to energy storage to medicine. The increasing exploitation of graphene-based materials (GBMs) necessitates a comprehensive evaluation of the potential impact of these materials on human health and the environment. Here, we discuss synthesis and characterization of GBMs as well as human and environmental hazard assessment of GBMs using in vitro and in vivo model systems with the aim to understand the properties that underlie the biol. effects of these materials; not all GBMs are alike, and it is essential that we disentangle the structure-activity relationships for this class of materials.
- 40Chortarea, S.; Kuru, O. C.; Netkueakul, W.; Pelin, M.; Keshavan, S.; Song, Z.; Ma, B.; Gómes, J.; Abalos, E. V.; Luna, L. A. V. de Hazard Assessment of Abraded Thermoplastic Composites Reinforced with Reduced Graphene Oxide. J. Hazard. Mater. 2022, 435, 129053 DOI: 10.1016/j.jhazmat.2022.129053Google Scholar40https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB38Xht1GjtLbO&md5=c6d41b6c20f872a84d69764a659ca81cHazard assessment of abraded thermoplastic composites reinforced with reduced graphene oxideChortarea, Savvina; Kuru, Ogul Can; Netkueakul, Woranan; Pelin, Marco; Keshavan, Sandeep; Song, Zhengmei; Ma, Baojin; Gomes, Julio; Abalos, Elvira Villaro; Luna, Luis Augusto Visani de; Loret, Thomas; Fordham, Alexander; Drummond, Matthew; Kontis, Nikolaos; Anagnostopoulos, George; Paterakis, George; Cataldi, Pietro; Tubaro, Aurelia; Galiotis, Costas; Kinloch, Ian; Fadeel, Bengt; Bussy, Cyrill; Kostarelos, Kostas; Buerki-Thurnherr, Tina; Prato, Maurizio; Bianco, Alberto; Wick, PeterJournal of Hazardous Materials (2022), 435 (), 129053CODEN: JHMAD9; ISSN:0304-3894. (Elsevier B.V.)Graphene-related materials (GRMs) are subject to intensive investigations and considerable progress has been made in recent years in terms of safety assessment. However, limited information is available concerning the hazard potential of GRM-contg. products such as graphene-reinforced composites. In the present study, we conducted a comprehensive investigation of the potential biol. effects of particles released through an abrasion process from reduced graphene oxide (rGO)-reinforced composites of polyamide 6 (PA6), a widely used engineered thermoplastic polymer, in comparison to as-produced rGO. First, a panel of well-established in vitro models, representative of the immune system and possible target organs such as the lungs, the gut, and the skin, was applied. Limited responses to PA6-rGO exposure were found in the different in vitro models. Only as-produced rGO induced substantial adverse effects, in particular in macrophages. Since inhalation of airborne materials is a key occupational concern, we then sought to test whether the in vitro responses noted for these materials would translate into adverse effects in vivo. To this end, the response at 1, 7 and 28 days after a single pulmonary exposure was evaluated in mice. In agreement with the in vitro data, PA6-rGO induced a modest and transient pulmonary inflammation, resolved by day 28. In contrast, rGO induced a longer-lasting, albeit moderate inflammation that did not lead to tissue remodeling within 28 days. Taken together, the present study suggests a negligible impact on human health under acute exposure conditions of GRM fillers such as rGO when released from composites at doses expected at the workplace.
- 41Schinwald, A.; Murphy, F. A.; Jones, A.; MacNee, W.; Donaldson, K. Graphene-Based Nanoplatelets: A New Risk to the Respiratory System as a Consequence of Their Unusual Aerodynamic Properties. ACS Nano 2012, 6, 736– 746, DOI: 10.1021/nn204229fGoogle Scholar41https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXhs1GrurnP&md5=d6893da59ca929cc9cd61bad2a6a5d24Graphene-Based Nanoplatelets: A New Risk to the Respiratory System as a Consequence of Their Unusual Aerodynamic PropertiesSchinwald, Anja; Murphy, Fiona A.; Jones, Alan; MacNee, William; Donaldson, KenACS Nano (2012), 6 (1), 736-746CODEN: ANCAC3; ISSN:1936-0851. (American Chemical Society)Graphene is a new nanomaterial with unusual and useful phys. and chem. properties. However, in the form of nanoplatelets this new, emerging material could pose unusual risks to the respiratory system after inhalation exposure. The graphene-based nanoplatelets used in this study are com. available and consist of several sheets of graphene (few-layer graphene). We first derived the respirability of graphene nanoplatelets (GP) from the basic principles of the aerodynamic behavior of plate-shaped particles which allowed us to calc. their aerodynamic diam. This showed that the nanoplatelets, which were up to 25 μm in diam., were respirable and so would deposit beyond the ciliated airways following inhalation. We therefore utilized models of pharyngeal aspiration and direct intrapleural installation of GP, as well as an in vitro model, to assess their inflammatory potential. These large but respirable GP were inflammogenic in both the lung and the pleural space. MIP-1α, MCP-1, MIP-2, IL-8, and IL-1β expression in the BAL, the pleural lavage, and cell culture supernatant from THP-1 macrophages were increased with GP exposure compared to controls but not with nanoparticulate carbon black (CB). In vitro, macrophages exposed to GP showed expression of IL-1β. This study highlights the importance of nanoplatelet form as a driver for in vivo and in vitro inflammogenicity by virtue of their respirable aerodynamic diam., despite a considerable 2-dimensional size which leads to frustrated phagocytosis when they deposit in the distal lungs and macrophages attempt to phagocytose them. Our data suggest that nanoplatelets pose a novel nanohazard and structure-toxicity relationship in nanoparticle toxicol.
- 42Mao, L.; Hu, M.; Pan, B.; Xie, Y.; Petersen, E. J. Biodistribution and Toxicity of Radio-Labeled Few Layer Graphene in Mice after Intratracheal Instillation. Part. Fibre Toxicol. 2015, 13 (1), 7, DOI: 10.1186/s12989-016-0120-1Google ScholarThere is no corresponding record for this reference.
- 43Park, E. J.; Lee, G. H.; Han, B. S.; Lee, B. S.; Lee, S.; Cho, M. H.; Kim, J. H.; Kim, D. W. Toxic Response of Graphene Nanoplatelets in Vivo and in Vitro. Arch. Toxicol. 2015, 89, 1557, DOI: 10.1007/s00204-014-1303-xGoogle Scholar43https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXhtVOns7jE&md5=6d48dfebf8a4527c2c11e8ad49b82ecdToxic response of graphene nanoplatelets in vivo and in vitroPark, Eun-Jung; Lee, Gwang-Hee; Han, Beom Seok; Lee, Byoung-Seok; Lee, Somin; Cho, Myung-Haing; Kim, Jae-Ho; Kim, Dong-WanArchives of Toxicology (2015), 89 (9), 1557-1568CODEN: ARTODN; ISSN:0340-5761. (Springer)With the development of nanotechnol., myriad types of novel materials have been discovered at the nanoscale, among which the most interesting material is graphene. However, the toxicity data available on graphene are extremely limited. In this study, we explored toxic response of com. available graphene nanoplatelets (GNPs) in vivo and in vitro. The GNPs used in this study had a high surface area and feature considerably few defects. In mice, GNPs (2.5 and 5 mg/kg) remained in the lung until 28 days after a single instillation, and the secretion of inflammatory cytokines reached the maximal level at Day 14 and then decreased over time. In vitro study using BEAS-2B cells, a human bronchial epithelial cell line, GNPs located within autophagosome-like vacuoles 24 h after exposure. The GNPs (2.5, 5, 10, and 20 μg/mL) also dose-dependently reduced cell viability, which was accompanied by an increase in the portion of cells in the subG1 and S phases. Moreover, the GNPs down-regulated the generation of reactive oxygen species, suppressed ATP prodn., caused mitochondria damage, and elevated the levels of autophagy-related proteins. Based on these results, we suggest that GNPs provoked a subchronic inflammatory response in mice and that GNPs induced autophagy accompanying apoptosis via mitochondria damage in vitro.
- 44Schinwald, A.; Murphy, F. A.; Askounis, A.; Koutsos, V.; Sefiane, K.; Donaldson, K.; Campbell, C. J. Minimal Oxidation and Inflammogenicity of Pristine Graphene with Residence in the Lung. Nanotoxicology 2014, 8, 824– 832, DOI: 10.3109/17435390.2013.831502Google Scholar44https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXhvFemtbfE&md5=b92ca597d53c67224de3562203d26575Minimal oxidation and inflammogenicity of pristine graphene with residence in the lungSchinwald, Anja; Murphy, Fiona; Askounis, Alexandros; Koutsos, Vasileios; Sefiane, Khellil; Donaldson, Ken; Campbell, Colin J.Nanotoxicology (2014), 8 (8), 824-832CODEN: NANOGK; ISSN:1743-5404. (Informa Healthcare)Two-dimensional graphitic carbon, graphene, is a new form of nanomaterial with great potential in a wide variety of applications. It is therefore crucial to investigate the behavior of graphene in biol. systems to assess potential adverse effects that might follow from inhalation exposure. In this study we focussed on medium-term effects of graphene in lung tissue by investigating the pulmonary inflammation 6 wk after pharyngeal aspiration of unoxidised multilayered graphene platelets (GPs) in mice and assessed their biopersistence in the lung tissue using Raman spectroscopy. Addnl., GP degrdn. in vitro was examd. after horseradish peroxidase (HRP) treatment up to 1 wk. Building on our previous report showing acute inflammation in mice lungs at 1 day, pristine GP showed minimal inflammation in mouse lungs after 6 wk even though no degrdn. of GP in lung tissue was obsd. and large deposits of GP were evident in the lungs. Raman anal. of GP in tissue sections showed minimal oxidn., and in vitro examns. of enzymic oxidn. of GP via HRP and H2O2 showed only slight increases in ID/IG ratio and the appearance of the Raman D' band at 1620 cm-1 (surrogates of graphene oxidn.). Our results showing non-inflammogenicity at medium time points have important implications in the hazard identification of GPs following inhalation exposure and for their use in biomedical applications. Addnl., the biopersistence of pristine GP in vivo with no assocd. inflammation could open the way to applications in tissue engineering and drug delivery.
- 45Shin, J. H.; Han, S. G.; Kim, J. K.; Kim, B. W.; Hwang, J. H.; Lee, J. S.; Lee, J. H.; Baek, J. E.; Kim, T. G.; Kim, K. S. 5-Day Repeated Inhalation and 28-Day Post-Exposure Study of Graphene. Nanotoxicology 2015, 9 (8), 1023– 1031, DOI: 10.3109/17435390.2014.998306Google Scholar45https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXhvVWqtr%252FI&md5=4483282f44e912e3c35fcf8d255dff365-Day repeated inhalation and 28-day post-exposure study of grapheneShin, Jae Hoon; Han, Sung Gu; Kim, Jin Kwon; Kim, Boo Wook; Hwang, Joo Hwan; Lee, Jong Seong; Lee, Ji Hyun; Baek, Jin Ee; Kim, Tae Gyu; Kim, Keun Soo; Lee, Heon Sang; Song, Nam Woong; Ahn, Kangho; Yu, Il JeNanotoxicology (2015), 9 (8), 1023-1031CODEN: NANOGK; ISSN:1743-5404. (Taylor & Francis Ltd.)Graphene has recently been attracting increasing attention due to its unique electronic and chem. properties and many potential applications in such fields as semiconductors, energy storage, flexible electronics, biosensors and medical imaging. However, the toxicity of graphene in the case of human exposure has not yet been clarified. Thus, a 5-day repeated inhalation toxicity study of graphene was conducted using a nose-only inhalation system for male Sprague-Dawley rats. A total of three groups (20 rats per group) were compared: (1) control (ambient air), (2) low concn. (0.68 ± 0.14 mg/m3 graphene) and (3) high concn. (3.86 ± 0.94 mg/m3 graphene). The rats were exposed to graphene for 6 h/day for 5 days, followed by recovery for 1, 3, 7 or 28 days. The bioaccumulation and macrophage ingestion of the graphene were evaluated in the rat lungs. The exposure to graphene did not change the body wts. or organ wts. of the rats after the 5-day exposure and during the recovery period. No statistically significant difference was obsd. in the levels of lactate dehydrogenase, protein and albumin between the exposed and control groups. However, graphene ingestion by alveolar macrophages was obsd. in the exposed groups. Therefore, these results suggest that the 5-day repeated exposure to graphene only had a minimal toxic effect at the concns. and time points used in this study.
- 46Kim, J. K.; Shin, J. H.; Lee, J. S.; Hwang, J. H.; Lee, J. H.; Baek, J. E.; Kim, T. G.; Kim, B. W.; Kim, J. S.; Lee, G. H. 28-Day Inhalation Toxicity of Graphene Nanoplatelets in Sprague-Dawley Rats. Nanotoxicology 2016, 10 (7), 891– 901, DOI: 10.3109/17435390.2015.1133865Google Scholar46https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28XisFGktrY%253D&md5=459f057b8d84c0771394c3d95247b14628-Day inhalation toxicity of graphene nanoplatelets in Sprague-Dawley ratsKim, Jin Kwon; Shin, Jae Hoon; Lee, Jong Seong; Hwang, Joo Hwan; Lee, Ji Hyun; Baek, Jin Ee; Kim, Tae Gyu; Kim, Boo Wook; Kim, Jin Sik; Lee, Gun Ho; Ahn, Kangho; Han, Sung Gu; Bello, Dhimiter; Yu, Il JeNanotoxicology (2016), 10 (7), 891-901CODEN: NANOGK; ISSN:1743-5404. (Taylor & Francis Ltd.)Graphene, a two-dimensional engineered nanomaterial, is now being used in many applications, such as electronics, biol. engineering, filtration, lightwt. and strong nanocomposite materials, and energy storage. However, there is a lack of information on the potential health effects of graphene in humans based on inhalation, the primary engineered nanomaterial exposure pathway in workplaces. Thus, an inhalation toxicol. study of graphene was conducted using a nose-only inhalation system for 28 days (6 h/day and 5 days/wk) with male Sprague-Dawley rats that were then allowed to recover for 1-, 28-, and 90-day post-exposure period. Animals were sepd. into 4 groups (control, low, moderate, and high) with 15 male rats (5 rats per time point) in each group. The measured mass concns. for the low, moderate, and high exposure groups were 0.12, 0.47, and 1.88 mg/m3, resp., very close to target concns. of 0.125, 0.5, and 2 mg/m3. Airborne graphene exposure was monitored using several real-time instrumentation over 10 nm to 20 μm for size distribution and no. concn. The total and respirable elemental carbon concns. were also measured using filter sampling. Graphene in the air and biol. media was traced using transmission electron microscopy. In addn. to mortality and clin. observations, the body wts. and food consumption were recorded weekly. At the end of the study, the rats were subjected to a full necropsy, blood samples were collected for blood biochem. tests, and the organ wts. were measured. No dose-dependent effects were recorded for the body wts., organ wts., bronchoalveolar lavage fluid inflammatory markers, and blood biochem. parameters at 1-day post-exposure and 28-day post-exposure. The inhaled graphenes were mostly ingested by macrophages. No distinct lung pathol. was obsd. at the 1-, 28- and 90-day post-exposure. The inhaled graphene was translocated to lung lymph nodes. The results of this 28-day graphene inhalation study suggest low toxicity and a NOAEL of no less than 1.88 mg/m3.
- 47Duch, M. C.; Budinger, G. R. S.; Liang, Y. T.; Soberanes, S.; Urich, D.; Chiarella, S. E.; Campochiaro, L. A.; Gonzalez, A.; Chandel, N. S.; Hersam, M. C. Minimizing Oxidation and Stable Nanoscale Dispersion Improves the Biocompatibility of Graphene in the Lung. Nano Lett. 2011, 11 (12), 5201– 5207, DOI: 10.1021/nl202515aGoogle Scholar47https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC38%252Fmt1ersw%253D%253D&md5=2901611a7f1af578ef7f0160bd2ee63dMinimizing oxidation and stable nanoscale dispersion improves the biocompatibility of graphene in the lungDuch Matthew C; Budinger G R Scott; Liang Yu Teng; Soberanes Saul; Urich Daniela; Chiarella Sergio E; Campochiaro Laura A; Gonzalez Angel; Chandel Navdeep S; Hersam Mark C; Mutlu Gokhan MNano letters (2011), 11 (12), 5201-7 ISSN:.To facilitate the proposed use of graphene and its derivative graphene oxide (GO) in widespread applications, we explored strategies that improve the biocompatibility of graphene nanomaterials in the lung. In particular, solutions of aggregated graphene, Pluronic dispersed graphene, and GO were administered directly into the lungs of mice. The introduction of GO resulted in severe and persistent lung injury. Furthermore, in cells GO increased the rate of mitochondrial respiration and the generation of reactive oxygen species, activating inflammatory and apoptotic pathways. In contrast, this toxicity was significantly reduced in the case of pristine graphene after liquid phase exfoliation and was further minimized when the unoxidized graphene was well-dispersed with the block copolymer Pluronic. Our results demonstrate that the covalent oxidation of graphene is a major contributor to its pulmonary toxicity and suggest that dispersion of pristine graphene in Pluronic provides a pathway for the safe handling and potential biomedical application of two-dimensional carbon nanomaterials.
- 48Li, R.; Guiney, L. M.; Chang, C. H.; Mansukhani, N. D.; Ji, Z.; Wang, X.; Liao, Y.-P. P.; Jiang, W.; Sun, B.; Hersam, M. C. Surface Oxidation of Graphene Oxide Determines Membrane Damage, Lipid Peroxidation, and Cytotoxicity in Macrophages in a Pulmonary Toxicity Model. ACS Nano 2018, 12 (2), 1390– 1402, DOI: 10.1021/acsnano.7b07737Google Scholar48https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1cXnvVCktw%253D%253D&md5=250124aed2894ca31da55bcaa2d3ce57Surface Oxidation of Graphene Oxide Determines Membrane Damage, Lipid Peroxidation, and Cytotoxicity in Macrophages in a Pulmonary Toxicity ModelLi, Ruibin; Guiney, Linda M.; Chang, Chong Hyun; Mansukhani, Nikhita D.; Ji, Zhaoxia; Wang, Xiang; Liao, Yu-Pei; Jiang, Wen; Sun, Bingbing; Hersam, Mark C.; Nel, Andre E.; Xia, TianACS Nano (2018), 12 (2), 1390-1402CODEN: ANCAC3; ISSN:1936-0851. (American Chemical Society)While two-dimensional graphene oxide (GO) is used increasingly in biomedical applications, there is uncertainty on how specific physicochem. properties relate to biocompatibility in mammalian systems. Although properties such as lateral size and the colloidal properties of the nanosheets are important, the specific material properties that we address here is the oxidn. state and reactive surface groups on the planar surface. In this study, we used a GO library, comprising pristine, reduced (rGO), and hydrated GO (hGO), in which quant. assessment of the hydroxyl, carboxyl, epoxy, and carbon radical contents was used to study the impact on epithelial cells and macrophages, as well as in the murine lung. Strikingly, we obsd. that hGO, which exhibits the highest carbon radical d., was responsible for the generation of cell death in THP-1 and BEAS-2B cells as a consequence of lipid peroxidn. of the surface membrane, membrane lysis, and cell death. In contrast, pristine GO had lesser effects, while rGO showed extensive cellular uptake with minimal effects on viability. In order to see how these in vitro effects relate to adverse outcomes in the lung, mice were exposed to GOs by oropharyngeal aspiration. Animal sacrifice after 40 h demonstrated that hGO was more prone than other materials to generate acute lung inflammation, accompanied by the highest lipid peroxidn. in alveolar macrophages, cytokine prodn. (LIX, MCP-1), and LDH release in bronchoalveolar lavage fluid. Pristine GO showed less toxicity, whereas rGO had minimal effects. We demonstrate that the surface oxidn. state and carbon radical content play major roles in the induction of toxicity by GO in mammalian cells and the lung.
- 49Bengtson, S.; Knudsen, K. B.; Kyjovska, Z. O.; Berthing, T.; Skaug, V.; Levin, M.; Koponen, I. K.; Shivayogimath, A.; Booth, T. J.; Alonso, B. Differences in Inflammation and Acute Phase Response but Similar Genotoxicity in Mice Following Pulmonary Exposure to Graphene Oxide and Reduced Graphene Oxide. PLoS One 2017, 12 (6), e0178355 DOI: 10.1371/journal.pone.0178355Google Scholar49https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXhslWhsr3M&md5=585e5fa50e54869664f3b270cb1c60cbDifferences in inflammation and acute phase response but similar genotoxicity in mice following pulmonary exposure to graphene oxide and reduced graphene oxideBengtson, Stefan; Knudsen, Kristina B.; Kyjovska, Zdenka O.; Berthing, Trine; Skaug, Vidar; Levin, Marcus; Koponen, Ismo K.; Shivayogimath, Abhay; Booth, Timothy J.; Alonso, Beatriz; Pesquera, Amaia; Zurutuza, Amaia; Thomsen, Birthe L.; Troelsen, Jesper T.; Jacobsen, Nicklas R.; Vogel, UllaPLoS One (2017), 12 (6), e0178355/1-e0178355/25CODEN: POLNCL; ISSN:1932-6203. (Public Library of Science)We investigated toxicity of 2-3 layered >1μm sized graphene oxide (GO) and reduced graphene oxide (rGO) in mice following single intratracheal exposure with respect to pulmonary inflammation, acute phase response (biomarker for risk of cardiovascular disease) and genotoxicity. In addn., we assessed exposure levels of particulate matter emitted during prodn. of graphene in a clean room and in a normal industrial environment using chem. vapor deposition. Toxicity was evaluated at day 1, 3, 28 and 90 days (18, 54 and 162μg/mouse), except for GO exposed mice at day 28 and 90 where only the lowest dose was evaluated. GO induced a strong acute inflammatory response together with a pulmonary (Serum-Amyloid A, Saa3) and hepatic (Saa1) acute phase response. rGO induced less acute, but a const. and prolonged inflammation up to day 90. Lung histopathol. showed particle agglomerates at day 90 without signs of fibrosis. In addn., DNA damage in BAL cells was obsd. across time points and doses for both GO and rGO. In conclusion, pulmonary exposure to GO and rGO induced inflammation, acute phase response and genotoxicity but no fibrosis.
- 50Wang, X.; Duch, M. C.; Mansukhani, N.; Ji, Z.; Liao, Y. P.; Wang, M.; Zhang, H.; Sun, B.; Chang, C. H.; Li, R. Use of a Pro-Fibrogenic Mechanism-Based Predictive Toxicological Approach for Tiered Testing and Decision Analysis of Carbonaceous Nanomaterials. ACS Nano 2015, 9, 3032, DOI: 10.1021/nn507243wGoogle Scholar50https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXitVers70%253D&md5=78c49c31d11bebfd86429a189471b242Use of a Pro-Fibrogenic Mechanism-Based Predictive Toxicological Approach for Tiered Testing and Decision Analysis of Carbonaceous NanomaterialsWang, Xiang; Duch, Matthew C.; Mansukhani, Nikhita; Ji, Zhaoxia; Liao, Yu-Pei; Wang, Meiying; Zhang, Haiyuan; Sun, Bingbing; Chang, Chong Hyun; Li, Ruibin; Lin, Sijie; Meng, Huan; Xia, Tian; Hersam, Mark C.; Nel, Andre E.ACS Nano (2015), 9 (3), 3032-3043CODEN: ANCAC3; ISSN:1936-0851. (American Chemical Society)Engineered carbonaceous nanomaterials (ECNs), including single-wall carbon nanotubes (SWCNTs), multiwall carbon nanotubes (MWCNTs), graphene, and graphene oxide (GO), are potentially hazardous to the lung. With incremental experience in the use of predictive toxicol. approaches, seeking to relate ECN physicochem. properties to adverse outcome pathways (AOPs), it is logical to explore the existence of a common AOP that allows comparative anal. of broad ECN categories. The authors established an ECN library comprising three different types of SWCNTs, graphene, and graphene oxide (two sizes) for comparative anal. according to a cell-based AOP that also plays a role in the pathogenesis of pulmonary fibrosis. SWCNTs synthesized by Hipco, arc discharge and Co-Mo catalyst (CoMoCAT) methods were obtained in their as-prepd. (AP) state, following which they were further purified (PD) or coated with Pluronic F108 (PF108) or bovine serum albumin (BSA) to improve dispersal and colloidal stability. GO was prepd. as two sizes, GO-small (S) and GO-large (L), while the graphene samples were coated with BSA and PF108 to enable dispersion in aq. soln. In vitro screening showed that AP- and PD-SWCNTs, irresp. of the method of synthesis, as well as graphene (BSA) and GO (S and L) could trigger interleukin-1β (IL-1β) and transforming growth factor-β1 (TGF-β1) prodn. in myeloid (THP-1) and epithelial (BEAS-2B) cell lines, resp. Oropharyngeal aspiration in mice confirmed that AP-Hipco tubes, graphene (BSA-dispersed), GO-S and GO-L could induce IL-1β and TGF-β1 prodn. in the lung in parallel with lung fibrosis. Notably, GO-L was the most pro-fibrogenic material based on rapid kinetics of pulmonary injury. In contrast, PF108-dispersed SWCNTs and -graphene failed to exert fibrogenic effects. Collectively, these data indicate that the dispersal state and surface reactivity of ECNs play key roles in triggering a pro-fibrogenic AOP, which could prove helpful for hazard ranking and a proposed tiered testing approach for large ECN categories.
- 51Vranic, S.; Rodrigues, A. F.; Buggio, M.; Newman, L.; White, M. R. H.; Spiller, D. G.; Bussy, C.; Kostarelos, K. Live Imaging of Label-Free Graphene Oxide Reveals Critical Factors Causing Oxidative-Stress-Mediated Cellular Responses. ACS Nano 2018, 12 (2), 1373– 1389, DOI: 10.1021/acsnano.7b07734Google Scholar51https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1cXhsFOisw%253D%253D&md5=2d227a016212a189d46e9b6055d2d48dLive Imaging of Label-Free Graphene Oxide Reveals Critical Factors Causing Oxidative-Stress-Mediated Cellular ResponsesVranic, Sandra; Rodrigues, Artur Filipe; Buggio, Maurizio; Newman, Leon; White, Michael R. H.; Spiller, David G.; Bussy, Cyrill; Kostarelos, KostasACS Nano (2018), 12 (2), 1373-1389CODEN: ANCAC3; ISSN:1936-0851. (American Chemical Society)The interest in graphene and its translation into com. products have been expanding at high pace. In regard to previously described pulmonary safety concerns for carbon nanomaterials, there is a great need to define parameters guiding interactions between graphene-based materials and pulmonary system. The aim of present study was to det. the importance of two crit. parameters: lateral dimensions of the material and coating with proteins in relation to each other and their pulmonary impact. Endotoxin-free materials with distinct lateral dimensions - s-GO (50 - 200 nm) and l-GO (5 - 15 μm) were produced and thoroughly characterized. Exploiting intrinsic fluorescence of GO and using confocal live-cell imaging, we visualized the behavior of the cells in response to the material in real time. Although BEAS-2B cells internalized GO efficiently, l-GO was linked to higher plasma membrane interactions correlated with elevated ROS levels, pro-inflammatory response and greater cytotoxicity, in agreement with the oxidative stress paradigm. For both GO types, the presence of serum alleviated lipid peroxidn. of plasma membrane and decreased intracellular ROS levels. However, protein coating was not enough to entirely mitigate toxicity and inflammatory response induced by l-GO. In vitro results were validated in vivo, as l-GO was more prone to induce pulmonary granulomatous response in mice compared to s-GO. In conclusion, lateral dimension of GO played more important role than serum protein coating in detg. biol. responses to the material. It was also demonstrated that time-lapse imaging of live cells interacting with label-free GO sheets can be used as a tool to assess GO induced cytotoxicity.
- 52Xu, S.; Zheng, H.; Ma, R.; Wu, D.; Pan, Y.; Yin, C.; Gao, M.; Wang, W.; Li, W.; Liu, S. Vacancies on 2D Transition Metal Dichalcogenides Elicit Ferroptotic Cell Death. Nat. Commun. 2020, 11 (1), 3484, DOI: 10.1038/s41467-020-17300-7Google Scholar52https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXhtl2rtr%252FE&md5=7edbe6c932e86048398d64166967c17fVacancies on 2D transition metal dichalcogenides elicit ferroptotic cell deathXu, Shujuan; Zheng, Huizhen; Ma, Ronglin; Wu, Di; Pan, Yanxia; Yin, Chunyang; Gao, Meng; Wang, Weili; Li, Wei; Liu, Sijin; Chai, Zhifang; Li, RuibinNature Communications (2020), 11 (1), 3484CODEN: NCAOBW; ISSN:2041-1723. (Nature Research)Sustainable developments of nanotechnol. necessitate the exploration of structure-activity relationships (SARs) at nano-bio interfaces. While ferroptosis may contribute in the developments of some severe diseases (e.g., Parkinson's disease, stroke and tumors), the cellular pathways and nano-SARs are rarely explored in diseases elicited by nano-sized ferroptosis inducers. Here we find that WS2 and MoS2 nanosheets induce an iron-dependent cell death, ferroptosis in epithelial (BEAS-2B) and macrophage (THP-1) cells, evidenced by the suppression of glutathione peroxidase 4 (GPX4), oxygen radical generation and lipid peroxidn. Notably, nano-SAR anal. of 20 transition metal dichalcogenides (TMDs) disclosures the decisive role of surface vacancy in ferroptosis. We therefore develop methanol and sulfide passivation as safe design approaches for TMD nanosheets. These findings are validated in animal lungs by oropharyngeal aspiration of TMD nanosheets. Overall, our study highlights the key cellular events as well as nano-SARs in TMD-induced ferroptosis, which may facilitate the safe design of nanoproducts.
- 53Moura, J. A.; Meldrum, K.; Doak, S. H.; Clift, M. J. D. Alternative Lung Cell Model Systems for Toxicology Testing Strategies: Current Knowledge and Future Outlook. Seminars in Cell and Developmental Biology. 2023, 147, 70, DOI: 10.1016/j.semcdb.2022.12.006Google Scholar53https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3sXjtFegsA%253D%253D&md5=82408004e001ba6d0f4a4926075bf1c3Alternative lung cell model systems for toxicology testing strategies: Current knowledge and future outlookMoura, Joana A.; Meldrum, Kirsty; Doak, Shareen H.; Clift, Martin J. D.Seminars in Cell & Developmental Biology (2023), 147 (), 70-82CODEN: SCDBFX; ISSN:1084-9521. (Elsevier Ltd.)A review. Due to the current relevance of pulmonary toxicol. (with focus upon air pollution and the inhalation of hazardous materials), it is important to further develop and implement physiol. relevant models of the entire respiratory tract. Lung model development has the aim to create human relevant systems that may replace animal use while balancing cost, laborious nature and regulatory ambition. There is an imperative need to move away from rodent models and implement models that mimic the holistic characteristics important in lung function. The purpose of this review is therefore, to describe and identify the various alternative models that are being applied towards assessing the pulmonary toxicol. of inhaled substances, as well as the current and potential developments of various advanced models and how they may be applied towards toxicol. testing strategies. These models aim to mimic various regions of the lung, as well as implementing different exposure methods with the addn. of various physiol. relevent conditions (such as fluid-flow and dynamic movement). There is further progress in the type of models used with focus on the development of lung-on-a-chip technologies and bioprinting, as well as and the optimization of such models to fill current knowledge gaps within toxicol.
- 54Murphy, F. A.; Poland, C. A.; Duffin, R.; Al-Jamal, K. T.; Nunes, A.; Ali-Boucetta, H.; Byrne, F.; Prina-Mello, A.; Volkov, Y.; Li, S. Length-Dependent Retention of Carbon Nanotubes in the Pleural Space of Mice Initiates Sustained Inflammation and Progressive Fibrosis on the Parietal Pleura. Am. J. Pathol. 2011, 178 (6), 2587– 2600, DOI: 10.1016/j.ajpath.2011.02.040Google Scholar54https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXoslOns74%253D&md5=5011ecbb060e9eab80668d88c468961fLength-dependent retention of carbon nanotubes in the pleural space of mice initiates sustained inflammation and progressive fibrosis on the parietal pleuraMurphy, Fiona A.; Poland, Craig A.; Duffin, Rodger; Al-Jamal, Khuloud T.; Ali-Boucetta, Hanene; Nunes, Antonio; Byrne, Fiona; Prina-Mello, Adriele; Volkov, Yuri; Li, Shouping; Mather, Stephen J.; Bianco, Alberto; Prato, Maurizio; MacNee, William; Wallace, William A.; Kostarelos, Kostas; Donaldson, KenAmerican Journal of Pathology (2011), 178 (6), 2587-2600CODEN: AJPAA4; ISSN:0002-9440. (Elsevier)The fibrous shape of carbon nanotubes (CNTs) raises concern that they may pose an asbestos-like inhalation hazard, leading to the development of diseases, esp. mesothelioma. Direct instillation of long and short CNTs into the pleural cavity, the site of mesothelioma development, produced asbestos-like length-dependent responses. The response to long CNTs and long asbestos was characterized by acute inflammation, leading to progressive fibrosis on the parietal pleura, where stomata of strictly defined size limit the egress of long, but not short, fibers. This was confirmed by demonstrating clearance of short, but not long, CNT and nickel nanowires and by visualizing the migration of short CNTs from the pleural space by single-photon emission computed tomog. imaging. Our data confirm the hypothesis that, although a proportion of all deposited particles passes through the pleura, the pathogenicity of long CNTs and other fibers arises as a result of length-dependent retention at the stomata on the parietal pleura.
- 55Schinwald, A.; Donaldson, K. Use of Back-Scatter Electron Signals to Visualise Cell/Nanowires Interactions in Vitro and in Vivo; Frustrated Phagocytosis of Long Fibres in Macrophages and Compartmentalisation in Mesothelial Cells in Vivo. Part. Fibre Toxicol. 2012, 9, 34, DOI: 10.1186/1743-8977-9-34Google Scholar55https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC38XhvVSiu73O&md5=4d21ebe21a7108af2de8e422014340c4Use of back-scatter electron signals to visualise cell/nanowires interactions in vitro and in vivo; frustrated phagocytosis of long fibres in macrophages and compartmentalisation in mesothelial cells in vivoSchinwald, Anja; Donaldson, KenParticle and Fibre Toxicology (2012), 9 (), 34CODEN: PFTABQ; ISSN:1743-8977. (BioMed Central Ltd.)Background: Frustrated phagocytosis has been stated as an important factor in the initiation of an inflammatory response after fiber exposure. The length of fibrous structures has been linked to the potential of fibers to induce adverse health effects for at least 40 years. However, we only recently reported for the first time the threshold length for fiber-induced inflammation in the pleural space and we implicated frustrated phagocytosis in the pro-inflammatory effects of long fibers. This study extends the examn. of the threshold value for frustrated phagocytosis using well-defined length classes of silver nanowires (AgNW) ranging from 3-28 μm and describes in detail the morphol. of frustrated phagocytosis using a novel technique and also describes compartmentalization of fibers in the pleural space. Methods: A novel technique, backscatter SEM (BSE) was used to study frustrated phagocytosis since it provides high-contrast detection of nanowires, allowing clear discrimination between the nanofibers and other cellular features. A human monocyte-derived macrophage cell line THP-1 was used to investigate cell-nanowire interaction in vitro and the parietal pleura, the site of fiber retention after inhalation exposure was chosen to visualize the cell-fiber interaction in vivo after direct pleural installation of AgNWs. Results: The length cut-off value for frustrated phagocytosis differs in vitro and in vivo. While in vitro frustrated phagocytosis could be obsd. with fibers ≥14 μm, in vivo studies showed incomplete uptake at a fiber length of ≥10 μm. Recently we showed that inflammation in the pleural space after intrapleural injection of the same nanofiber panel occurs at a length of ≥5 μm. This onset of inflammation does not correlate with the onset of frustrated phagocytosis as shown in this study, leading to the conclusion that intermediate length fibers fully enclosed within macrophages as well as frustrated phagocytosis are assocd. with a pro-inflammatory state in the pleural space. We further showed that fibers compartmentalize in the mesothelial cells at the parietal pleura as well as in inflammatory cells in the pleural space. Conclusion: BSE is a useful way to clearly distinguish between fibers that are, or are not, membrane-bounded. Using this method we were able to show differences in the threshold length at which frustrated phagocytosis occurred between in vitro and in vivo models. Visualising nanowires in the pleura demonstrated at least 2 compartments - in leukocyte aggregations and in the mesothelium - which may have consequences for long term pathol. in the pleural space including mesothelioma.
- 56Liu, Y.; Zhao, Y.; Sun, B.; Chen, C. Understanding the Toxicity of Carbon Nanotubes. Acc. Chem. Res. 2013, 46 (3), 702– 713, DOI: 10.1021/ar300028mGoogle Scholar56https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC38Xhtl2iurbO&md5=9d1c85c6d394bff5f9d2c4ec1da97f25Understanding the toxicity of carbon nanotubesLiu, Ying; Zhao, Yuliang; Sun, Baoyun; Chen, ChunyingAccounts of Chemical Research (2013), 46 (3), 702-713CODEN: ACHRE4; ISSN:0001-4842. (American Chemical Society)A review. Because of their unique phys., chem., elec., and mech. properties, carbon nanotubes (CNTs) have attracted a great deal of research interest and have many potential applications. As large-scale prodn. and application of CNTs increases, the general population is more likely to be exposed to CNTs either directly or indirectly, which has prompted considerable attention about human health and safety issues related to CNTs. Although considerable exptl. data related to CNT toxicity at the mol., cellular, and whole animal levels have been published, the results are often conflicting. Therefore, a systematic understanding of CNT toxicity is needed but has not yet been developed. In this Account, we highlight recent investigations into the basis of CNT toxicity carried out by our team and by other labs. We focus on several important factors that explain the disparities in the exptl. results of nanotoxicity, such as impurities, amorphous carbon, surface charge, shape, length, agglomeration, and layer nos. The exposure routes, including inhalation, i.v. injection, or dermal or oral exposure, can also influence the in vivo behavior and fate of CNTs. The underlying mechanisms of CNT toxicity include oxidative stress, inflammatory responses, malignant transformation, DNA damage and mutation (errors in chromosome no. as well as disruption of the mitotic spindle), the formation of granulomas, and interstitial fibrosis. These findings provide useful insights for de novo design and safe application of carbon nanotubes and their risk assessment to human health. To obtain reproducible and accurate results, researchers must establish stds. and reliable detection methods, use std. CNT samples as a ref. control, and study the impact of various factors systematically. In addn., researchers need to examine multiple types of CNTs, different cell lines and animal species, multidimensional evaluation methods, and exposure conditions. To make results comparable among different institutions and countries, researchers need to standardize choices in toxicity testing such as that of cell line, animal species, and exposure conditions. The knowledge presented here should lead to a better understanding of the key factors that can influence CNT toxicity so that their unwanted toxicity might be avoided.
- 57Murphy, F. A.; Poland, C. A.; Duffin, R.; Al-Jamal, K. T.; Nunes, A.; Ali-Boucetta, H.; Byrne, F.; Prina-Mello, A.; Volkov, Y.; Li, S. Length-Dependent Retention of Carbon Nanotubes in the Pleural Space of Mice Initiates Sustained Inflammation and Progressive Fibrosis on the Parietal Pleura. Am. J. Pathol. 2011, 178, 2587– 2600, DOI: 10.1016/j.ajpath.2011.02.040Google Scholar57https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXoslOns74%253D&md5=5011ecbb060e9eab80668d88c468961fLength-dependent retention of carbon nanotubes in the pleural space of mice initiates sustained inflammation and progressive fibrosis on the parietal pleuraMurphy, Fiona A.; Poland, Craig A.; Duffin, Rodger; Al-Jamal, Khuloud T.; Ali-Boucetta, Hanene; Nunes, Antonio; Byrne, Fiona; Prina-Mello, Adriele; Volkov, Yuri; Li, Shouping; Mather, Stephen J.; Bianco, Alberto; Prato, Maurizio; MacNee, William; Wallace, William A.; Kostarelos, Kostas; Donaldson, KenAmerican Journal of Pathology (2011), 178 (6), 2587-2600CODEN: AJPAA4; ISSN:0002-9440. (Elsevier)The fibrous shape of carbon nanotubes (CNTs) raises concern that they may pose an asbestos-like inhalation hazard, leading to the development of diseases, esp. mesothelioma. Direct instillation of long and short CNTs into the pleural cavity, the site of mesothelioma development, produced asbestos-like length-dependent responses. The response to long CNTs and long asbestos was characterized by acute inflammation, leading to progressive fibrosis on the parietal pleura, where stomata of strictly defined size limit the egress of long, but not short, fibers. This was confirmed by demonstrating clearance of short, but not long, CNT and nickel nanowires and by visualizing the migration of short CNTs from the pleural space by single-photon emission computed tomog. imaging. Our data confirm the hypothesis that, although a proportion of all deposited particles passes through the pleura, the pathogenicity of long CNTs and other fibers arises as a result of length-dependent retention at the stomata on the parietal pleura.
- 58Osmond-McLeod, M. J.; Poland, C. A.; Murphy, F.; Waddington, L.; Morris, H.; Hawkins, S. C.; Clark, S.; Aitken, R.; McCall, M. J.; Donaldson, K. Durability and Inflammogenic Impact of Carbon Nanotubes Compared with Asbestos Fibres. Part. Fibre Toxicol. 2011, 8, 15, DOI: 10.1186/1743-8977-8-15Google Scholar58https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXmt1Omur4%253D&md5=a8ae6fd962c052f8b7511bc65c88bce3Durability and inflammogenic impact of carbon nanotubes compared with asbestos fibresOsmond-McLeod, Megan J.; Poland, Craig A.; Murphy, Fiona; Waddington, Lynne; Morris, Howard; Hawkins, Stephen C.; Clark, Steve; Aitken, Rob; McCall, Maxine J.; Donaldson, KenParticle and Fibre Toxicology (2011), 8 (), 15CODEN: PFTABQ; ISSN:1743-8977. (BioMed Central Ltd.)Background: It has been suggested that carbon nanotubes might conform to the fiber pathogenicity paradigm that explains the toxicities of asbestos and other fibers on a continuum based on length, aspect ratio and biopersistence. Some types of carbon nanotubes satisfy the first two aspects of the fiber paradigm but only recently has their biopersistence begun to be investigated. Biopersistence is complex and requires in vivo testing and anal. However durability, the chem. mimicking of the process of fiber dissoln. using in vitro treatment, is closely related to biopersistence and more readily detd. Here, we describe an exptl. process to det. the durability of four types of carbon nanotubes in simulated biol. fluid (Gambles soln.), and their subsequent pathogenicity in vivo using a mouse model sensitive to inflammogenic effects of fibers. The in vitro and in vivo results were compared with well-characterized glass wool and asbestos fiber controls. Results: After incubation for up to 24 wk in Gambles soln., our control fibers were recovered at percentages consistent with their known in vitro durabilities and/or in vivo persistence, and three out of the four types of carbon nanotubes tested [single walled (CNTSW) and multi walled (CNTTANG2, CNTSPIN)] showed no, or minimal, loss of mass or change in fiber length or morphol. when examd. by electron microscopy. However, the fourth type [multi walled (CNTLONG1)] lost 30% of its original mass within the first three weeks of incubation, after which there was no further loss. Electron microscopy of CNTLONG1 samples incubated for 10 wk confirmed that the proportion of long fibers had decreased compared to samples briefly exposed to the Gambles soln. This loss of mass and fiber shortening was accompanied by a loss of pathogenicity when injected into the peritoneal cavities of C57Bl/6 mice compared to fibers incubated briefly. CNTSW did not elicit an inflammogenic effect in the peritoneal cavity assay used here. Conclusions: These results support the view that carbon nanotubes are generally durable but may be subject to bio-modification in a sample-specific manner. They also suggest that pristine carbon nanotubes, either individually or in rope-like aggregates of sufficient length and aspect ratio, can induce asbestos-like responses in mice, but that the effect may be mitigated for certain types that are less durable in biol. systems. Results indicate that durable carbon nanotubes that are either short or form tightly bundled aggregates with no isolated long fibers are less inflammogenic in fiber specific assays.
- 59Gieseck, R. L.; Wilson, M. S.; Wynn, T. A. Type 2 Immunity in Tissue Repair and Fibrosis. Nature Reviews Immunology. 2018, 18, 62– 76, DOI: 10.1038/nri.2017.90Google Scholar59https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXhtl2ru7fI&md5=9b306b272e5e70589d4fb0c2432ef5d8Type 2 immunity in tissue repair and fibrosisGieseck, Richard L., III; Wilson, Mark S.; Wynn, Thomas A.Nature Reviews Immunology (2018), 18 (1), 62-76CODEN: NRIABX; ISSN:1474-1733. (Nature Research)Type 2 immunity is characterized by the prodn. of IL-4, IL-5, IL-9 and IL-13, and this immune response is commonly obsd. in tissues during allergic inflammation or infection with helminth parasites. However, many of the key cell types assocd. with type 2 immune responses - including T helper 2 cells, eosinophils, mast cells, basophils, type 2 innate lymphoid cells and IL-4- and IL-13-activated macrophages - also regulate tissue repair following injury. Indeed, these cell populations engage in crucial protective activity by reducing tissue inflammation and activating important tissue-regenerative mechanisms. Nevertheless, when type 2 cytokine-mediated repair processes become chronic, over-exuberant or dysregulated, they can also contribute to the development of pathol. fibrosis in many different organ systems. In this Review, we discuss the mechanisms by which type 2 immunity contributes to tissue regeneration and fibrosis following injury.
- 60Wynn, T. A. Fibrotic Disease and the TH1/TH2 Paradigm. Nature Reviews Immunology. 2004, 4, 583– 594, DOI: 10.1038/nri1412Google Scholar60https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD2cXmtFWktr0%253D&md5=eb3bd245546d25a3e06df136bfe2602aFibrotic disease and the TH1/TH2 paradigmWynn, Thomas A.Nature Reviews Immunology (2004), 4 (8), 583-594CODEN: NRIABX; ISSN:1474-1733. (Nature Publishing Group)A review. Tissue fibrosis (scarring) is a leading cause of morbidity and mortality. Current treatments for fibrotic disorders, such as idiopathic pulmonary fibrosis, hepatic fibrosis and systemic sclerosis, target the inflammatory cascade, but they have been widely unsuccessful, largely because the mechanisms that are involved in fibrogenesis are now known to be distinct from those involved in inflammation. Several exptl. models have recently been developed to dissect the mol. mechanisms of wound healing and fibrosis. It is hoped that by better understanding the immunol. mechanisms that initiate, sustain and suppress the fibrotic process, the authors will achieve the elusive goal of targeted and effective therapeutics for fibroproliferative diseases.
- 61Wynn, T. A.; Vannella, K. M. Macrophages in Tissue Repair, Regeneration, and Fibrosis. Immunity. 2016, 44, 450– 462, DOI: 10.1016/j.immuni.2016.02.015Google Scholar61https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28Xktlahs70%253D&md5=bb0e131d752c2c6fd017fb25aad5ee08Macrophages in Tissue Repair, Regeneration, and FibrosisWynn, Thomas A.; Vannella, Kevin M.Immunity (2016), 44 (3), 450-462CODEN: IUNIEH; ISSN:1074-7613. (Elsevier Inc.)Inflammatory monocytes and tissue-resident macrophages are key regulators of tissue repair, regeneration, and fibrosis. After tissue injury, monocytes and macrophages undergo marked phenotypic and functional changes to play crit. roles during the initiation, maintenance, and resoln. phases of tissue repair. Disturbances in macrophage function can lead to aberrant repair, such that uncontrolled prodn. of inflammatory mediators and growth factors, deficient generation of anti-inflammatory macrophages, or failed communication between macrophages and epithelial cells, endothelial cells, fibroblasts, and stem or tissue progenitor cells all contribute to a state of persistent injury, and this could lead to the development of pathol. fibrosis. In this review, we discuss the mechanisms that instruct macrophages to adopt pro-inflammatory, pro-wound-healing, pro-fibrotic, anti-inflammatory, anti-fibrotic, pro-resolving, and tissue-regenerating phenotypes after injury, and we highlight how some of these mechanisms and macrophage activation states could be exploited therapeutically.
- 62Fadeel, B.; Kostarelos, K. Grouping All Carbon Nanotubes into a Single Substance Category Is Scientifically Unjustified. Nature Nanotechnology. 2020, 15, 164, DOI: 10.1038/s41565-020-0654-0Google Scholar62https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXktFelsr4%253D&md5=26bf8c8a8a419d8be2ca5129f66d4bd4Grouping all carbon nanotubes into a single substance category is scientifically unjustifiedFadeel, Bengt; Kostarelos, KostasNature Nanotechnology (2020), 15 (3), 164CODEN: NNAABX; ISSN:1748-3387. (Nature Research)There is no expanded citation for this reference.
- 63Del Rio Castillo, A. E.; Pellegrini, V.; Ansaldo, A.; Ricciardella, F.; Sun, H.; Marasco, L.; Buha, J.; Dang, Z.; Gagliani, L.; Lago, E. High-Yield Production of 2D Crystals by Wet-Jet Milling. Mater. Horizons 2018, 5 (5), 890– 904, DOI: 10.1039/C8MH00487KGoogle Scholar63https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1cXht1OjtLzM&md5=279c9077c7e2002ff0f973c2f80ab5feHigh-yield production of 2D crystals by wet-jet millingDel Rio Castillo, A. E.; Pellegrini, V.; Ansaldo, A.; Ricciardella, F.; Sun, H.; Marasco, L.; Buha, J.; Dang, Z.; Gagliani, L.; Lago, E.; Curreli, N.; Gentiluomo, S.; Palazon, F.; Prato, M.; Oropesa-Nunez, R.; Toth, P. S.; Mantero, E.; Crugliano, M.; Gamucci, A.; Tomadin, A.; Polini, M.; Bonaccorso, F.Materials Horizons (2018), 5 (5), 890-904CODEN: MHAOBM; ISSN:2051-6355. (Royal Society of Chemistry)Efficient and scalable prodn. of two-dimensional (2D) materials is required to overcome technol. hurdles towards the creation of a 2D-material-based industry. Here, we present a novel approach developed for the exfoliation of layered crystals, i.e., graphite, hexagonal-boron nitride and transition metal dichalcogenides. The process is based on high-pressure wet-jet-milling (WJM), resulting in a 2 L h-1 prodn. of 10 g L-1 of single- and few-layer 2D crystal flakes in dispersion making the scaling-up more affordable. The WJM process enables the prodn. of defect-free and high quality 2D-crystal dispersions on a large scale, opening the way for their full exploitation in different com. applications, e.g., as anode active material in lithium ion batteries, as reinforcement in polymer-graphene composites, and as conductive inks, as we demonstrate in this report.
- 64Del Rio Castillo, A. E.; Ansaldo, A.; Pellegrini, V.; Bonaccorso, F. US Patent Exfoliation of Layered Materials by Wet-Jet Milling Techniques. US10407308B2, 2019.Google ScholarThere is no corresponding record for this reference.
- 65Smith, M. W.; Jordan, K. C.; Park, C.; Kim, J. W.; Lillehei, P. T.; Crooks, R.; Harrison, J. S. Very Long Single-and Few-Walled Boron Nitride Nanotubes via the Pressurized Vapor/Condenser Method. Nanotechnology 2009, 20 (50), 505604, DOI: 10.1088/0957-4484/20/50/505604Google Scholar65https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1MXhs1SrtL7P&md5=e66ba9b2a408739155497c2670ece6faVery long single- and few-walled boron nitride nanotubes via the pressurized vapor/condenser methodSmith, Michael W.; Jordan, Kevin C.; Park, Cheol; Kim, Jae-Woo; Lillehei, Peter T.; Crooks, Roy; Harrison, Joycelyn S.Nanotechnology (2009), 20 (50), 505604/1-505604/6CODEN: NNOTER; ISSN:1361-6528. (Institute of Physics Publishing)A new method for producing long, small-diam., single- and few-walled, boron nitride nanotubes (BNNTs) in macroscopic quantities is reported. The pressurized vapor/condenser (PVC) method produces, without catalysts, highly cryst., very long, small-diam., BNNTs. Palm-sized, cotton-like masses of BNNT raw material were grown by this technique and spun directly into centimeters-long yarn. Nanotube lengths were obsd. to be 100 times that of those grown by the most closely related method. Self-assembly and growth models for these long BNNTs are discussed.
- 66Gutruf, P.; Yin, R. T.; Lee, K. B.; Ausra, J.; Brennan, J. A.; Qiao, Y.; Xie, Z.; Peralta, R.; Talarico, O.; Murillo, A. Wireless, Battery-Free, Fully Implantable Multimodal and Multisite Pacemakers for Applications in Small Animal Models. Nat. Commun. 2019, 10 (1), 5742, DOI: 10.1038/s41467-019-13637-wGoogle Scholar66https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1MXisVGjsb%252FE&md5=4d1b76d9078c7e23171fea0ff4766b9fWireless, battery-free, fully implantable multimodal and multisite pacemakers for applications in small animal modelsGutruf, Philipp; Yin, Rose T.; Lee, K. Benjamin; Ausra, Jokubas; Brennan, Jaclyn A.; Qiao, Yun; Xie, Zhaoqian; Peralta, Roberto; Talarico, Olivia; Murillo, Alejandro; Chen, Sheena W.; Leshock, John P.; Haney, Chad R.; Waters, Emily A.; Zhang, Changxing; Luan, Haiwen; Huang, Yonggang; Trachiotis, Gregory; Efimov, Igor R.; Rogers, John A.Nature Communications (2019), 10 (1), 5742CODEN: NCAOBW; ISSN:2041-1723. (Nature Research)Small animals support a wide range of pathol. phenotypes and genotypes as versatile, affordable models for pathogenesis of cardiovascular diseases and for exploration of strategies in electrotherapy, gene therapy, and optogenetics. Pacing tools in such contexts are currently limited to tethered embodiments that constrain animal behaviors and exptl. designs. Here, we introduce a highly miniaturized wireless energy-harvesting and digital communication electronics for thin, miniaturized pacing platforms weighing 110 mg with capabilities for subdermal implantation and tolerance to over 200,000 multiaxial cycles of strain without degrdn. in elec. or optical performance. Multimodal and multisite pacing in ex vivo and in vivo studies over many days demonstrate chronic stability and excellent biocompatibility. Optogenetic stimulation of cardiac cycles with in-animal control and induction of heart failure through chronic pacing serve as examples of modes of operation relevant to fundamental and applied cardiovascular research and biomedical technol.
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Abstract
Figure 1
Figure 1. Structural characterization of h-BN and BNNTs. (a) TEM image of h-BN. (b) AFM image of h-BN. (c,d) Lateral size (LogNorm. SD 0.797, N = 159) and thickness distributions (LogNorm. SD 1.054, N = 129) of h-BN nanosheets. (e) TEM image of BNNTs. (f) AFM image of BNNTs. (g) Diameter distribution of walls for BNNTs (black and red bars correspond to internal and external diameters, respectively). (h) Number of walls for BNNTs.
Figure 2
Figure 2. Evaluation of boron nitride distribution and clearance using scanning Raman spectroscopy. Mice were exposed by single oropharyngeal aspiration to 30 μg of h-BN or BNNTs. One, 7, and 28 days after the last exposure, left lungs were collected, inflated with formalin, embedded in paraffin, and then processed (n = 5). Lung sections (5 μm) were dewaxed and scanned using scanning Raman spectroscopy. h-BN and BNNTs were identified based on the Raman shift at 1370 cm–1. (a) Overlay of Raman intensities and bright-field images are presented. (b) Variation of boron (1370 cm–1) intensity over time.
Figure 3
Figure 3. Influx of inflammatory cells in alveolar space. Mice were exposed by oropharyngeal aspiration to 30 μg of h-BN, BNNTs, or to control (vehicle and LPS). BALFs were collected on days 1, 7, and 28, cytospun on slides, and then differentially stained for cell phenotyping. (a) Cell population in BALFs. (b) Total number of immune cells. (c) Number of mononucleated macrophages, multinucleated macrophages, neutrophils, eosinophils, and lymphocytes in BALF. Two-way ANOVA followed by Tukey’s multiple comparisons test was used to evaluate statistical differences compared to the negative control (p < 0.05 (*), p < 0.01 (**), p < 0.001 (***)).
Figure 4
Figure 4. Inflammatory response in lungs. (a) Evaluation of inflammatory markers levels in lungs by multiplex ELISA (log2 fold change). (I) Acute inflammation; (II) late pro-inflammatory response; (III) anti-inflammatory response; (IV) adaptive immune activation. (b) Evaluation of SAA3, Arg-1, and osteopontin levels by RT-qPCR. One-way ANOVA followed by Dunnett posthoc test was used to evaluate any statistical difference between normalized cytokine concentrations (pg/mg of total protein measured with Pierce Assay) or fold change compared to the negative control (n = 5; (*) p < 0.05, (**) p < 0.01, (***) p < 0.001).
Figure 5
Figure 5. Histopathological changes in lungs. Mice were exposed to h-BN, BNNTs, or controls. (a) Lung sections were stained in hematoxylin and eosin for histopathological analysis. (b) Bronchial and pleural thicknesses were recorded. Immune infiltrates (green arrow), and granulomatous-like structures (yellow arrow) were identified and measured. Two-way ANOVA followed by Tukey’s multiple comparisons test was used to evaluate statistical differences between materials exposure and the negative control (n = 5; p < 0.05 (*), p < 0.01 (**), p < 0.001 (***)).
Figure 6
Figure 6. Fibrosis and DNA damage in the lungs. Mice were exposed to h-BN, BNNTs, or controls; lungs were collected after 28 days. (a) Lung sections were stained with Masson’s Trichrome, then collagen deposition was evaluated using MATLAB. (b) Lung sections from day 28 were immunostained for γ-H2AX to evaluate DNA double-strand breaks and potential long-term genotoxicity. One-way ANOVA followed by Dunett’s posthoc test was used to evaluate statistical differences between h-BN or BNNTs and the negative control (n = 5; p < 0.05 (*), p < 0.01 (**), p < 0.001 (***)).
References
This article references 66 other publications.
- 1Ferrari, A. C.; Bonaccorso, F.; Fal’ko, V.; Novoselov, K. S.; Roche, S.; Bøggild, P.; Borini, S.; Koppens, F. H. L.; Palermo, V.; Pugno, N. Science and Technology Roadmap for Graphene, Related Two-Dimensional Crystals, and Hybrid Systems. Nanoscale 2015, 7 (11), 4598, DOI: 10.1039/C4NR01600A1https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXhsFyhu77K&md5=65926c599802eaf69f8e1b3160cc0189Science and technology roadmap for graphene, related two-dimensional crystals, and hybrid systemsFerrari, Andrea C.; Bonaccorso, Francesco; Fal'ko, Vladimir; Novoselov, Konstantin S.; Roche, Stephan; Boeggild, Peter; Borini, Stefano; Koppens, Frank H. L.; Palermo, Vincenzo; Pugno, Nicola; Garrido, Jose A.; Sordan, Roman; Bianco, Alberto; Ballerini, Laura; Prato, Maurizio; Lidorikis, Elefterios; Kivioja, Jani; Marinelli, Claudio; Ryhanen, Tapani; Morpurgo, Alberto; Coleman, Jonathan N.; Nicolosi, Valeria; Colombo, Luigi; Fert, Albert; Garcia-Hernandez, Mar; Bachtold, Adrian; Schneider, Gregory F.; Guinea, Francisco; Dekker, Cees; Barbone, Matteo; Sun, Zhipei; Galiotis, Costas; Grigorenko, Alexander N.; Konstantatos, Gerasimos; Kis, Andras; Katsnelson, Mikhail; Vandersypen, Lieven; Loiseau, Annick; Morandi, Vittorio; Neumaier, Daniel; Treossi, Emanuele; Pellegrini, Vittorio; Polini, Marco; Tredicucci, Alessandro; Williams, Gareth M.; Hee Hong, Byung; Ahn, Jong-Hyun; Min Kim, Jong; Zirath, Herbert; van Wees, Bart J.; van der Zant, Herre; Occhipinti, Luigi; Di Matteo, Andrea; Kinloch, Ian A.; Seyller, Thomas; Quesnel, Etienne; Feng, Xinliang; Teo, Ken; Rupesinghe, Nalin; Hakonen, Pertti; Neil, Simon R. T.; Tannock, Quentin; Lofwander, Tomas; Kinaret, JariNanoscale (2015), 7 (11), 4598-4810CODEN: NANOHL; ISSN:2040-3372. (Royal Society of Chemistry)A review. We present the science and technol. roadmap for graphene, related two-dimensional crystals, and hybrid systems, targeting an evolution in technol., that might lead to impacts and benefits reaching into most areas of society. This roadmap was developed within the framework of the European Graphene Flagship and outlines the main targets and research areas as best understood at the start of this ambitious project. We provide an overview of the key aspects of graphene and related materials (GRMs), ranging from fundamental research challenges to a variety of applications in a large no. of sectors, highlighting the steps necessary to take GRMs from a state of raw potential to a point where they might revolutionize multiple industries. We also define an extensive list of acronyms in an effort to standardize the nomenclature in this emerging field.
- 2Roy, S.; Zhang, X.; Puthirath, A. B.; Meiyazhagan, A.; Bhattacharyya, S.; Rahman, M. M.; Babu, G.; Susarla, S.; Saju, S. K.; Tran, M. K. Structure, Properties and Applications of Two-Dimensional Hexagonal Boron Nitride. Adv. Mater. 2021, 2101589, DOI: 10.1002/adma.2021015892https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3MXitFamsL3I&md5=5b8700c618d1863245f70e6125db36cbStructure, Properties and Applications of Two-Dimensional Hexagonal Boron NitrideRoy, Soumyabrata; Zhang, Xiang; Puthirath, Anand B.; Meiyazhagan, Ashokkumar; Bhattacharyya, Sohini; Rahman, Muhammad M.; Babu, Ganguli; Susarla, Sandhya; Saju, Sreehari K.; Tran, Mai Kim; Sassi, Lucas M.; Saadi, M. A. S. R.; Lai, Jiawei; Sahin, Onur; Sajadi, Seyed Mohammad; Dharmarajan, Bhuvaneswari; Salpekar, Devashish; Chakingal, Nithya; Baburaj, Abhijit; Shuai, Xinting; Adumbumkulath, Aparna; Miller, Kristen A.; Gayle, Jessica M.; Ajnsztajn, Alec; Prasankumar, Thibeorchews; Harikrishnan, Vijay Vedhan Jayanthi; Ojha, Ved; Kannan, Harikishan; Khater, Ali Zein; Zhu, Zhenwei; Iyengar, Sathvik Ajay; Autreto, Pedro Alves da Silva; Oliveira, Eliezer Fernando; Gao, Guanhui; Birdwell, A. Glen; Neupane, Mahesh R.; Ivanov, Tony G.; Taha-Tijerina, Jaime; Yadav, Ram Manohar; Arepalli, Sivaram; Vajtai, Robert; Ajayan, Pulickel M.Advanced Materials (Weinheim, Germany) (2021), 33 (44), 2101589CODEN: ADVMEW; ISSN:0935-9648. (Wiley-VCH Verlag GmbH & Co. KGaA)A review. Hexagonal BN (h-BN) has emerged as a strong candidate for 2-dimensional (2D) material owing to its exciting optoelec. properties combined with mech. robustness, thermal stability, and chem. inertness. Super-thin h-BN layers have gained significant attention from the scientific community for many applications, including nanoelectronics, photonics, biomedical, anti-corrosion, and catalysis, among others. A systematic elaboration of the structural, elec., mech., optical, and thermal properties of h-BN followed by a comprehensive account of state-of-the-art synthesis strategies for 2D h-BN, including chem. exfoliation, chem., and phys. vapor deposition, and other methods that were developed in recent years is provided. It further elaborates a wide variety of processing routes developed for doping, substitution, functionalization, and combination with other materials to form heterostructures. Based on the extraordinary properties and thermal-mech.-chem. stability of 2D h-BN, various potential applications of these structures are described.
- 3Falin, A.; Cai, Q.; Santos, E. J. G.; Scullion, D.; Qian, D.; Zhang, R.; Yang, Z.; Huang, S.; Watanabe, K.; Taniguchi, T. Mechanical Properties of Atomically Thin Boron Nitride and the Role of Interlayer Interactions. Nat. Commun. 2017, 8, 15815, DOI: 10.1038/ncomms158153https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXhtVCrt7zO&md5=ed5133678a75d0e8f9ea40ca54279028Mechanical properties of atomically thin boron nitride and the role of interlayer interactionsFalin, Aleksey; Cai, Qiran; Santos, Elton J. G.; Scullion, Declan; Qian, Dong; Zhang, Rui; Yang, Zhi; Huang, Shaoming; Watanabe, Kenji; Taniguchi, Takashi; Barnett, Matthew R.; Chen, Ying; Ruoff, Rodney S.; Li, Lu HuaNature Communications (2017), 8 (), 15815CODEN: NCAOBW; ISSN:2041-1723. (Nature Publishing Group)Atomically thin boron nitride (BN) nanosheets are important two-dimensional nanomaterials with many unique properties distinct from those of graphene, but investigation into their mech. properties remains incomplete. Here we report that high-quality single-cryst. mono- and few-layer BN nanosheets are one of the strongest elec. insulating materials. More intriguingly, few-layer BN shows mech. behaviors quite different from those of few-layer graphene under indentation. In striking contrast to graphene, whose strength decreases by more than 30% when the no. of layers increases from 1 to 8, the mech. strength of BN nanosheets is not sensitive to increasing thickness. We attribute this difference to the distinct interlayer interactions and hence sliding tendencies in these two materials under indentation. The significantly better interlayer integrity of BN nanosheets makes them a more attractive candidate than graphene for several applications, for example, as mech. reinforcements.
- 4Liu, Z.; Gong, Y.; Zhou, W.; Ma, L.; Yu, J.; Idrobo, J. C.; Jung, J.; Macdonald, A. H.; Vajtai, R.; Lou, J. Ultrathin Higherature Oxidation-Resistant Coatings of Hexagonal Boron Nitride. Nat. Commun. 2013, 4, 2541, DOI: 10.1038/ncomms35414https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC2c%252FlvFGhsw%253D%253D&md5=489e725fdc37a25d1e2454ccd4ea053cUltrathin high-temperature oxidation-resistant coatings of hexagonal boron nitrideLiu Zheng; Gong Yongji; Zhou Wu; Ma Lulu; Yu Jingjiang; Idrobo Juan Carlos; Jung Jeil; MacDonald Allan H; Vajtai Robert; Lou Jun; Ajayan Pulickel MNature communications (2013), 4 (), 2541 ISSN:.Hexagonal boron nitride is a two-dimensional layered material that can be stable at 1,500 °C in air and will not react with most chemicals. Here we demonstrate large-scale, ultrathin, oxidation-resistant coatings of high-quality hexagonal boron nitride layers with controlled thicknesses from double layers to bulk. We show that such ultrathin hexagonal boron nitride films are impervious to oxygen diffusion even at high temperatures and can serve as high-performance oxidation-resistant coatings for nickel up to 1,100 °C in oxidizing atmospheres. Furthermore, graphene layers coated with a few hexagonal boron nitride layers are also protected at similarly high temperatures. These hexagonal boron nitride atomic layer coatings, which can be synthesized via scalable chemical vapour deposition method down to only two layers, could be the thinnest coating ever shown to withstand such extreme environments and find applications as chemically stable high-temperature coatings.
- 5Li, L. H.; Chen, Y. Atomically Thin Boron Nitride: Unique Properties and Applications. Adv. Funct. Mater. 2016, 26 (16), 2594– 2608, DOI: 10.1002/adfm.2015046065https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28XisFKhu7w%253D&md5=fa274a0a9feec8a58dd3bcfc22374536Atomically Thin Boron Nitride: Unique Properties and ApplicationsLi, Lu Hua; Chen, YingAdvanced Functional Materials (2016), 26 (16), 2594-2608CODEN: AFMDC6; ISSN:1616-301X. (Wiley-VCH Verlag GmbH & Co. KGaA)Atomically thin boron nitride (BN) is an important 2D nanomaterial, with many properties distinct from graphene. In this feature article, these unique properties and assocd. applications, often not feasible with graphene, are outlined. The article starts with characterization and identification of atomically thin BN. It is followed by demonstrating their strong oxidn. resistance at high temps. and applications in protecting metals from oxidn. and corrosion. As flat insulators, BN nanosheets are ideal dielec. substrates for surface enhanced Raman spectroscopy (SERS) and electronic devices based on 2D heterostructures. The light emission of BN nanosheets in the deep UV (DUV) and UV regions is also included for its scientific and technol. importance. The last part is dedicated to synthesis, characterization, and optical properties of BN nanoribbons, a special form of nanosheets.
- 6Cai, Q.; Du, A.; Gao, G.; Mateti, S.; Cowie, B. C. C.; Qian, D.; Zhang, S.; Lu, Y.; Fu, L.; Taniguchi, T. Molecule-Induced Conformational Change in Boron Nitride Nanosheets with Enhanced Surface Adsorption. Adv. Funct. Mater. 2016, 26 (45), 8202– 8210, DOI: 10.1002/adfm.2016031606https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28XhsVaksbvL&md5=4e422ad215b9acf0672223e761fffeedMolecule-Induced Conformational Change in Boron Nitride Nanosheets with Enhanced Surface AdsorptionCai, Qiran; Du, Aijun; Gao, Guoping; Mateti, Srikanth; Cowie, Bruce C. C.; Qian, Dong; Zhang, Shuang; Lu, Yuerui; Fu, Lan; Taniguchi, Takashi; Huang, Shaoming; Chen, Ying; Ruoff, Rodney S.; Li, Lu HuaAdvanced Functional Materials (2016), 26 (45), 8202-8210CODEN: AFMDC6; ISSN:1616-301X. (Wiley-VCH Verlag GmbH & Co. KGaA)Surface interaction is extremely important to both fundamental research and practical application. Physisorption can induce shape and structural distortion (i.e., conformational changes) in macromol. and biomol. adsorbates, but such phenomena have rarely been obsd. on adsorbents. Here, it is demonstrated theor. and exptl. that atomically thin boron nitride (BN) nanosheets as an adsorbent experience conformational changes upon surface adsorption of mols., increasing adsorption energy and efficiency. The study not only provides new perspectives on the strong adsorption capability of BN nanosheets and many other two-dimensional (2D) nanomaterials but also opens up possibilities for many novel applications. For example, it is demonstrated that BN nanosheets with the same surface area as bulk hexagonal BN particles are more effective in purifn. and sensing.
- 7Kim, J. H.; Pham, T. V.; Hwang, J. H.; Kim, C. S.; Kim, M. J. Boron Nitride Nanotubes: Synthesis and Applications. Nano Convergence. 2018, 17, DOI: 10.1186/s40580-018-0149-y7https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1cXhvV2lt7rO&md5=3cb832818fe56dbed4f1be15ad46af28Boron nitride nanotubes: synthesis and applicationsKim, Jun Hee; Pham, Thang Viet; Hwang, Jae Hun; Kim, Cheol Sang; Kim, Myung JongNano Convergence (2018), 5 (1), 17/1-17/13CODEN: NCAOCX; ISSN:2196-5404. (SpringerOpen)Boron nitride nanotube (BNNT) has similar tubular nanostructure as carbon nanotube (CNT) in which boron and nitrogen atoms arranged in a hexagonal network. Owing to the unique at. structure, BNNT has numerous excellent intrinsic properties such as superior mech. strength, high thermal cond., elec. insulating behavior, piezoelec. property, neutron shielding capability, and oxidn. resistance. Since BNNT was first synthesized in 1995, developing efficient BNNT prodn. route has been a significant issue due to low yield and poor quality in comparison with CNT, thus limiting its practical uses. However, many great successes in BNNT synthesis have been achieved in recent years, enabling access to this material and paving the way for the development of promising applications. In this article, we discussed current progress in the prodn. of boron nitride nanotube, focusing on the most common and effective methods that have been well established so far. In addn., we presented various applications of BNNT including polymer composite reinforcement, thermal management packages, piezo actuators, and neutron shielding nanomaterial.
- 8Zhan, Y.; Lago, E.; Santillo, C.; Del Río Castillo, A. E.; Hao, S.; Buonocore, G. G.; Chen, Z.; Xia, H.; Lavorgna, M.; Bonaccorso, F. An Anisotropic Layer-by-Layer Carbon Nanotube/Boron Nitride/Rubber Composite and Its Application in Electromagnetic Shielding. Nanoscale 2020, 12 (14), 7782– 7791, DOI: 10.1039/C9NR10672C8https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXkvF2ksro%253D&md5=44f10394d87d1d646b3708bcc50e5b02An anisotropic layer-by-layer carbon nanotube/boron nitride/rubber composite and its application in electromagnetic shieldingZhan, Yanhu; Lago, Emanuele; Santillo, Chiara; Del Rio Castillo, Antonio Esau; Hao, Shuai; Buonocore, Giovanna G.; Chen, Zhenming; Xia, Hesheng; Lavorgna, Marino; Bonaccorso, FrancescoNanoscale (2020), 12 (14), 7782-7791CODEN: NANOHL; ISSN:2040-3372. (Royal Society of Chemistry)Multifunctional polymer composites with anisotropic properties are attracting interest as they fulfil the growing demand of multitasking materials. In this work, anisotropic polymer composites have been fabricated by combining the layer-by-layer (LBL) filtration method with the alternative assembling of carbon nanotubes (CNTs) and hexagonal boron nitride flakes (hBN) on natural rubber latex particles (NR). The layered composites exhibit anisotropic thermal and elec. conductivities, which are tailored through the layer formulations. The best composite consists of four layers of NR modified with 8 phr (parts per hundred rubber) CNTs (~ 7.4 wt%) and four alternate layers with 12 phr hBN (~ 10.7 wt%). The composites exhibit an electromagnetic interference (EMI) shielding effectiveness of 22.41 ± 0.14 dB mm-1 at 10.3 GHz and a thermal cond. equal to 0.25 W m-1 K-1. Furthermore, when the layered composite is used as an elec. thermal heater the surface reaches a stable temp. of ~ 103°C in approx. 2 min, with an input bias of 2.5 V.
- 9Ren, J.; Stagi, L.; Carbonaro, C. M.; Malfatti, L.; Casula, M. F.; Ricci, P. C.; Del Rio Castillo, A. E.; Bonaccorso, F.; Calvillo, L.; Granozzi, G. Defect-Assisted Photoluminescence in Hexagonal Boron Nitride Nanosheets. 2D Mater. 2020, 7, 045023, DOI: 10.1088/2053-1583/ababf09https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXit1Sqs7rN&md5=5e75331fd8e7add20b14bd0ecda3c44eDefect-assisted photoluminescence in hexagonal boron nitride nanosheetsRen, Junkai; Stagi, Luigi; Carbonaro, Carlo Maria; Malfatti, Luca; Casula, Maria Francesca; Ricci, Pier Carlo; Del Rio Castillo, Antonio Esau; Bonaccorso, Francesco; Calvillo, Laura; Granozzi, Gaetano; Innocenzi, Plinio2D Materials (2020), 7 (4), 045023CODEN: DMATB7; ISSN:2053-1583. (IOP Publishing Ltd.)The development of functional optoelectronic applications based on hexagonal boron nitride nanosheets (h-BNNs) relies on controlling the structural defects. The fluorescent emission, in particular, has been obsd. to depend on vacancies and substitutional defects. In the present work, few-layer h-BNNs have been obtained by sonication-assisted liq.-phase exfoliation of their bulk counterpart. The as-prepd. samples exhibit a weak fluorescent emission in the visible range, centered around 400 nm. Tailored defects have been introduced by oxidn. in air at different temps. A significant increase in the fluorescent emission of the oxidated h-BNNs has been obsd. with max. emissive intensity for the samples treated at 300°C. A further increase in temps. (>300°C) dets. a quenching of the fluorescence. We investigated, by means of detailed microscopic and spectroscopic anal., the relationship between the optical properties and defects of h-BNNs. The investigation of the optical properties as a function of treatment temp. highlights the crit. role of hydroxyl groups created by the oxidn. process. Only h-BN exfoliated in water allows introducing OH groups with consequent enhancement of fluorescence emission.
- 10Kodali, V. K.; Roberts, J. R.; Shoeb, M.; Wolfarth, M. G.; Bishop, L.; Eye, T.; Barger, M.; Roach, K. A.; Friend, S.; Schwegler-Berry, D. Acute in Vitro and in Vivo Toxicity of a Commercial Grade Boron Nitride Nanotube Mixture. Nanotoxicology 2017, 11 (8), 1040– 1058, DOI: 10.1080/17435390.2017.139017710https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXhslGksbrN&md5=fe4af51818e7798b7502e1f44dd6bc19Acute in vitro and in vivo toxicity of a commercial grade boron nitride nanotube mixtureKodali, Vamsi K.; Roberts, Jenny R.; Shoeb, Mohammad; Wolfarth, Michael G.; Bishop, Lindsey; Eye, Tracy; Barger, Mark; Roach, Katherine A.; Friend, Sherri; Schwegler-Berry, Diane; Chen, Bean T.; Stefaniak, Aleksandr; Jordan, Kevin C.; Whitney, Roy R.; Porter, Dale W.; Erdely, Aaron D.Nanotoxicology (2017), 11 (8), 1040-1058CODEN: NANOGK; ISSN:1743-5404. (Taylor & Francis Ltd.)Boron nitride nanotubes (BNNTs) are an emerging engineered nanomaterial attracting significant attention due to superior elec., chem. and thermal properties. Currently, the toxicity profile of this material is largely unknown. Com. grade BNNTs are composed of a mixt. (BNNT-M) of ∼50-60% BNNTs, and ∼40-50% impurities of boron and hexagonal boron nitride. We performed acute in vitro and in vivo studies with com. grade BNNT-M, dispersed by sonication in vehicle, in comparison to the extensively studied multiwalled carbon nanotube-7 (MWCNT-7). THP-1 wild-type and NLRP3-deficient human monocytic cells were exposed to 0-100 μg/mL and C57BL/6 J male mice were treated with 40 μg of BNNT-M for in vitro and in vivo studies, resp. In vitro, BNNT-M induced a dose-dependent increase in cytotoxicity and oxidative stress. This was confirmed in vivo following acute exposure increase in bronchoalveolar lavage levels of lactate dehydrogenase, pulmonary polymorphonuclear cell influx, loss in mitochondrial membrane potential and augmented levels of 4-hydroxynonenal. Uptake of this material caused lysosomal destabilization, pyroptosis and inflammasome activation, corroborated by an increase in cathepsin B, caspase 1, increased protein levels of IL-1β and IL-18 both in vitro and in vivo. Attenuation of these effects in NLRP3-deficient THP-1 cells confirmed NLRP3-dependent inflammasome activation by BNNT-M. BNNT-M induced a similar profile of inflammatory pulmonary protein prodn. when compared to MWCNT-7. Functionally, pretreatment with BNNT-M caused suppression in bacterial uptake by THP-1 cells, an effect that was mirrored in challenged alveolar macrophages collected from exposed mice and attenuated with NLRP3 deficiency. Anal. of cytokines secreted by LPS-challenged alveolar macrophages collected after in vivo exposure to dispersions of BNNT-M showed a differential macrophage response. The obsd. results demonstrated acute inflammation and toxicity in vitro and in vivo following exposure to sonicated BNNT-M was in part due to NLRP3 inflammasome activation.
- 11Xin, X.; Barger, M.; Roach, K. A.; Bowers, L.; Stefaniak, A. B.; Kodali, V.; Glassford, E.; Dunn, K. L.; Dunn, K. H.; Wolfarth, M. Toxicity Evaluation Following Pulmonary Exposure to an As-Manufactured Dispersed Boron Nitride Nanotube (BNNT) Material in Vivo. NanoImpact 2020, 19, 100235, DOI: 10.1016/j.impact.2020.100235There is no corresponding record for this reference.
- 12Dong, J. Signaling Pathways Implicated in Carbon Nanotube-Induced Lung Inflammation. Frontiers in Immunology. 2020, 552613, DOI: 10.3389/fimmu.2020.55261312https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3MXlvFeqsrw%253D&md5=416f3f1414974e79cc4831bc91662f50Signaling pathways implicated in carbon nanotube-induced lung inflammationDong, JieFrontiers in Immunology (2020), 11 (), 552613CODEN: FIRMCW; ISSN:1664-3224. (Frontiers Media S.A.)A review. Inflammation is a tissue response to a variety of harmful stimuli, such as pathogens, irritants, and injuries, and can eliminate insults and limit tissue damage. However, dysregulated inflammation is recognized as a cause of many human diseases, exemplified by organ fibrosis and cancer. In this regard, inflammation-promoted fibrosis is commonly obsd. in human lung diseases, such as idiopathic pulmonary fibrosis and pneumoconiosis. Carbon nanotubes (CNTs) are a type of nanomaterials with unique properties and various industrial and com. applications. On the other hand, certain forms of CNTs are potent inducers of inflammation and fibrosis in animal lungs. Notably, acute inflammation is a remarkable phenotype elicited by CNTs in the lung during the early acute phase post-exposure; whereas a type 2 immune response is evidently activated and dominates during the late acute and chronic phases, leading to type 2 inflammation and lung fibrosis. Numerous studies demonstrate that these immune responses involve distinct immune cells, various pathol. factors, and specific functions and play crucial roles in the initiation and progression of inflammation and fibrosis in the lung exposed to CNTs. Thus, the mechanistic understanding of the immune responses activated by CNTs has drawn great attention in recent years. This article reviews the major findings on the cell signaling pathways that are activated in immune cells and exert functions in promoting immune responses in CNT-exposed lungs, which would provide new insights into the understanding of CNT-induced lung inflammation and inflammation-driven fibrosis, the application of CNT-induced lung inflammation and fibrosis as a new disease model, and the potential of targeting immune cells as a therapeutic strategy for relevant human lung diseases.
- 13Dong, J.; Ma, Q. Type 2 Immune Mechanisms in Carbon Nanotube-Induced Lung Fibrosis. Frontiers in Immunology. 2018, 9, 1120, DOI: 10.3389/fimmu.2018.0112013https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1cXit1GjsLfM&md5=f6f896b5fd8985b3a879cadd64d5eaf7Type 2 immune mechanisms in carbon nanotube-induced lung fibrosisDong, Jie; Ma, QiangFrontiers in Immunology (2018), 9 (), 1120/1-1120/17CODEN: FIRMCW; ISSN:1664-3224. (Frontiers Media S.A.)A review. T helper (Th) 2-dependent type 2 immune pathways have been recognized as an important driver for the development of fibrosis. Upon stimulation, activated Th2 immune cells and type 2 cytokines interact with inflammatory and tissue repair functions to stimulate an overzealous reparative response to tissue damage, leading to organ fibrosis and destruction. In this connection, type 2 pathways are activated by a variety of insults and pathol. conditions to modulate the response. Carbon nanotubes (CNTs) are nanomaterials with a wide range of applications. However, pulmonary exposure to CNTs causes a no. of pathol. outcomes in animal lungs, dominated by inflammation and fibrosis. These findings, alongside the rapidly expanding prodn. and commercialization of CNTs and CNT-contg. materials in recent years, have raised concerns on the health risk of CNT exposure in humans. The CNT-induced pulmonary fibrotic lesions resemble those of human fibrotic lung diseases, such as idiopathic pulmonary fibrosis and pneumoconiosis, to a certain extent with regard to disease development and pathol. features. In fibrotic scenarios, immune cells are activated including varying immune pathways, ranging from innate immune cell activation to autoimmune disease. These events often precede and/or accompany the occurrence of fibrosis. Upon CNT exposure, significant induction and activation of Th2 cells and type 2 cytokines in the lungs are obsd. Moreover, type 2 pathways are shown to play important roles in promoting CNT-induced lung fibrosis by producing type 2 pro-fibrotic factors and inducing the reparative phenotypes of macrophages in response to CNTs. In light of the vastly increased demand for nanosafety and the apparent induction and multiple roles of type 2 immune pathways in lung fibrosis, we review the current literature on CNT-induced lung fibrosis, with a focus on the induction and activation of type 2 responses by CNTs and the stimulating function of type 2 signaling on pulmonary fibrosis development. These analyses provide new insights into the mechanistic understanding of CNT-induced lung fibrosis, as well as the potential of using type 2 responses as a monitoring target and therapeutic strategy for human fibrotic lung disease.
- 14Kasai, T.; Umeda, Y.; Ohnishi, M.; Mine, T.; Kondo, H.; Takeuchi, T.; Matsumoto, M.; Fukushima, S. Lung Carcinogenicity of Inhaled Multi-Walled Carbon Nanotube in Rats. Part. Fibre Toxicol. 2015, 13 (1), 53, DOI: 10.1186/s12989-016-0164-2There is no corresponding record for this reference.
- 15Sakamoto, Y.; Hojo, M.; Kosugi, Y.; Watanabe, K.; Hirose, A.; Inomata, A.; Suzuki, T.; Nakae, D. Comparative Study for Carcinogenicity of 7 Different Multi-Wall Carbon Nanotubes with Different Physicochemical Characteristics by a Single Intraperitoneal Injection in Male Fischer 344 Rats. J. Toxicol. Sci. 2018, 43 (10), 587– 600, DOI: 10.2131/jts.43.58715https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXhtlOnu77K&md5=1833680dbebee46138d6d1a3d2f39fc2Comparative study for carcinogenicity of 7 different multi-wall carbon nanotubes with different physicochemical characteristics by a single intraperitoneal injection in male Fischer 344 ratsSakamoto, Yoshimitsu; Hojo, Motoki; Kosugi, Yuki; Watanabe, Kimiyo; Hirose, Akihiko; Inomata, Akiko; Suzuki, Toshinari; Nakae, DaiJournal of Toxicological Sciences (2018), 43 (10), 587-600CODEN: JTSCDR; ISSN:0388-1350. (Japanese Society of Toxicology)The present study comparatively examd. carcinogenicity of 7 different multi-wall carbon nanotubes (MWCNTs) with different physicochem. characteristics. Physicochem. characteristics of MWCNTs (referred to as M-, N-, WL-, SD1-, WS-, SD2- and T-CNTs in the present study) were detd. using scanning electron and light microscopes and a collision type inductively coupled plasma mass spectrometer. Male Fischer 344 rats (10 wk old, 15 animals per group) were administered MWCNTs at a single i.p. dose of 1 mg/kg body wt., and sacrificed up to 52 wk after the commencement. Fibers of M-, N-, WL- and SD1-CNTs were straight and acicular in shape, and contained few agglomerates. They were relatively long (38-59% of fibers were longer than 5μm) and thick (33% to more than 70% of fibers were thicker than 60 nm). Fibers of WS-, SD2- and T-CNTs were curled and tightly tangled to form frequent agglomerates. They were relatively short and thin (more than 90% of measured fibers were thinner than 50 nm). WS- CNT did not induce mesothelioma, and only one of 15 rat given SD2- or T-CNT developed tumor. Any correlations existed between the metal content and neither the size or form of fibers, nor the carcinogenicity. The straight and acicular shape without frequent agglomerates, and the relatively long and thick size, but not the iron content, may be crit. factors. The present data can contribute to the risk management, practical use and social acceptance of MWCNTs.
- 16Kodali, V.; Roberts, J. R.; Glassford, E.; Gill, R.; Friend, S.; Dunn, K. L.; Erdely, A. Understanding Toxicity Associated with Boron Nitride Nanotubes: Review of Toxicity Studies, Exposure Assessment at Manufacturing Facilities, and Read-Across. J. Mater. Res. 2022, 37, 4620– 4638, DOI: 10.1557/s43578-022-00796-816https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB38Xisl2qtbzI&md5=12a33f72c50013a8870051bcb350f10fUnderstanding toxicity associated with boron nitride nanotubes: Review of toxicity studies, exposure assessment at manufacturing facilities, and read-acrossKodali, Vamsi; Roberts, Jenny R.; Glassford, Eric; Gill, Ryan; Friend, Sherri; Dunn, Kevin L.; Erdely, AaronJournal of Materials Research (2022), 37 (24), 4620-4638CODEN: JMREEE; ISSN:2044-5326. (Springer International Publishing AG)A review. Boron nitride nanotubes (BNNT) are produced by many different methods leading to variances in physicochem. characteristics and impurities in the final product. These differences can alter the toxicity profile. The importance of understanding the potential pathol. implications of this high aspect ratio nanomaterial is increasing as new approaches to synthesize and purify in large scale are being developed. In this review, we discuss the various factors of BNNT prodn. that can influence its toxicity followed by summarizing the toxicity findings from in vitro and in vivo studies conducted to date, including a review of particle clearance obsd. with various exposure routes. To understand the risk to workers and interpret relevance of toxicol. findings, exposure assessment at manufg. facilities was discussed. Workplace exposure assessment of BNNT from two manufg. facilities measured boron concns. in personal breathing zones from non-detectable to 0.95μg/m3 and TEM structure counts of 0.0123 ± 0.0094 structures/cm3, concns. well below what was found with other engineered high aspect ratio nanomaterials like carbon nanotubes and nanofibers. Finally, using a purified BNNT, a "read-across" toxicity assessment was performed to demonstrate how known hazard data and physicochem. characteristics can be utilized to evaluate potential inhalation toxicity concerns.
- 17Lucherelli, M. A.; Qian, X.; Weston, P.; Eredia, M.; Zhu, W.; Samorì, P.; Gao, H.; Bianco, A.; von dem Bussche, A. Boron Nitride Nanosheets Can Induce Water Channels Across Lipid Bilayers Leading to Lysosomal Permeabilization. Adv. Mater. 2021, 33 (45), 2103137, DOI: 10.1002/adma.20210313717https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3MXitFans7%252FJ&md5=0d4512d28ba902bffaddbe8705739229Boron Nitride Nanosheets Can Induce Water Channels Across Lipid Bilayers Leading to Lysosomal PermeabilizationLucherelli, Matteo Andrea; Qian, Xuliang; Weston, Paula; Eredia, Matilde; Zhu, Wenpeng; Samori, Paolo; Gao, Huajian; Bianco, Alberto; von dem Bussche, AnnetteAdvanced Materials (Weinheim, Germany) (2021), 33 (45), 2103137CODEN: ADVMEW; ISSN:0935-9648. (Wiley-VCH Verlag GmbH & Co. KGaA)While the interaction between 2D materials and cells is of key importance to the development of nanomedicines and safe applications of nanotechnol., still little is known about the biol. interactions of many emerging 2D materials. Here, an investigation of how hexagonal boron nitride (hBN) interacts with the cell membrane is carried out by combining mol. dynamics (MD), liq.-phase exfoliation, and in vitro imaging methods. MD simulations reveal that a sharp hBN wedge can penetrate a lipid bilayer and form a cross-membrane water channel along its exposed polar edges, while a round hBN sheet does not exhibit this behavior. It is hypothesized that such water channels can facilitate cross-membrane transport, with important consequences including lysosomal membrane permeabilization, an emerging mechanism of cellular toxicity that involves the release of cathepsin B and generation of radical oxygen species leading to cell apoptosis. To test this hypothesis, two types of hBN nanosheets, one with a rhomboidal, cornered morphol. and one with a round morphol., are prepd., and human lung epithelial cells are exposed to both materials. The cornered hBN with lateral polar edges results in a dose-dependent cytotoxic effect, whereas round hBN does not cause significant toxicity, thus confirming our premise.
- 18Kodali, V.; Kim, K. S.; Roberts, J. R.; Bowers, L.; Wolfarth, M. G.; Hubczak, J.; Xin, X.; Eye, T.; Friend, S.; Stefaniak, A. B. Influence of Impurities from Manufacturing Process on the Toxicity Profile of Boron Nitride Nanotubes. Small 2022, 18 (52), 2203259, DOI: 10.1002/smll.20220325918https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB38XivFSit7rI&md5=b716e0226709b9e83003e7bd39b90984Influence of Impurities from Manufacturing Process on the Toxicity Profile of Boron Nitride NanotubesKodali, Vamsi; Kim, Keun Su; Roberts, Jenny R.; Bowers, Lauren; Wolfarth, Michael G.; Hubczak, John; Xin, Xing; Eye, Tracy; Friend, Sherri; Stefaniak, Aleksandr B.; Leonard, Stephen S.; Jakubinek, Michael; Erdely, AaronSmall (2022), 18 (52), 2203259CODEN: SMALBC; ISSN:1613-6810. (Wiley-VCH Verlag GmbH & Co. KGaA)The toxicity of boron nitride nanotubes (BNNTs) has been the subject of conflicting reports, likely due to differences in the residuals and impurities that can make up to 30-60% of the material produced based on the manufg. processes and purifn. employed. Four BNNTs manufd. by induction thermal plasma process with a gradient of BNNT purity levels achieved through sequential gas purifn., water and solvent washing, allowed assessing the influence of these residuals/impurities on the toxicity profile of BNNTs. Extensive characterization including IR and X-ray spectroscopy, thermogravimetric anal., size, charge, surface area, and d. captured the alteration in physicochem. properties as the material went through sequential purifn. The material from each step is screened using acellular and in vitro assays for evaluating general toxicity, mechanisms of toxicity, and macrophage function. As the material increased in purity, there are more high-aspect-ratio particulates and a corresponding distinct increase in cytotoxicity, nuclear factor-κB transcription, and inflammasome activation. There is no alteration in macrophage function after BNNT exposure with all purity grades. The cytotoxicity and mechanism of screening clustered with the purity grade of BNNTs, illustrating that greater purity of BNNT corresponds to greater toxicity.
- 19Donaldson, K.; Murphy, F. A.; Duffin, R.; Poland, C. A. Asbestos, Carbon Nanotubes and the Pleural Mesothelium: A Review of the Hypothesis Regarding the Role of Long Fibre Retention in the Parietal Pleura, Inflammation and Mesothelioma. Part. Fibre Toxicol. 2010, 7, 5, DOI: 10.1186/1743-8977-7-519https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC3c3nsF2jtg%253D%253D&md5=49db73fee80b155964e544fd639835b8Asbestos, carbon nanotubes and the pleural mesothelium: a review of the hypothesis regarding the role of long fibre retention in the parietal pleura, inflammation and mesotheliomaDonaldson Ken; Murphy Fiona A; Duffin Rodger; Poland Craig AParticle and fibre toxicology (2010), 7 (), 5 ISSN:.The unique hazard posed to the pleural mesothelium by asbestos has engendered concern in potential for a similar risk from high aspect ratio nanoparticles (HARN) such as carbon nanotubes. In the course of studying the potential impact of HARN on the pleura we have utilised the existing hypothesis regarding the role of the parietal pleura in the response to long fibres. This review seeks to synthesise our new data with multi-walled carbon nanotubes (CNT) with that hypothesis for the behaviour of long fibres in the lung and their retention in the parietal pleura leading to the initiation of inflammation and pleural pathology such as mesothelioma. We describe evidence that a fraction of all deposited particles reach the pleura and that a mechanism of particle clearance from the pleura exits, through stomata in the parietal pleura. We suggest that these stomata are the site of retention of long fibres which cannot negotiate them leading to inflammation and pleural pathology including mesothelioma. We cite thoracoscopic data to support the contention, as would be anticipated from the preceding, that the parietal pleura is the site of origin of pleural mesothelioma. This mechanism, if it finds support, has important implications for future research into the mesothelioma hazard from HARN and also for our current view of the origins of asbestos-initiated pleural mesothelioma and the common use of lung parenchymal asbestos fibre burden as a correlate of this tumour, which actually arises in the parietal pleura.
- 20Donaldson, K.; Murphy, F.; Schinwald, A.; Duffin, R.; Poland, C. A. Identifying the Pulmonary Hazard of High Aspect Ratio Nanoparticles to Enable Their Safety-by-Design. Nanomedicine 2011, 6 (1), 143– 156, DOI: 10.2217/nnm.10.13920https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3cXhs1WntbbO&md5=2bd96d8dc669b6d2f6be2fbc0000978fIdentifying the pulmonary hazard of high aspect ratio nanoparticles to enable their safety-by-designDonaldson, Ken; Murphy, Fiona; Schinwald, Anja; Duffin, Rodger; Poland, Craig A.Nanomedicine (London, United Kingdom) (2011), 6 (1), 143-156CODEN: NLUKAC; ISSN:1743-5889. (Future Medicine Ltd.)A review. High aspect ratio, or fiber-shaped, nanoparticles (HARNs) represent a growth area in nanotechnol. as their useful properties become more apparent. Carbon nanotubes, the best known and studied of the HARNs are handled on an increasingly large scale, with subsequent potential for human inhalation exposure. Their resemblance to asbestos fibers pptd. fears that they might show the same type of pathol. as that caused by asbestos and there is emerging evidence to support this possibility. The large no. of other HARNs, including nanorods, nanowires and other nanofibers, require similar toxicol. scrutiny. In this article we describe the unusual hazard assocd. with fibers, with special ref. to asbestos, and address the features of fibers that dictate their pathogenicity as developed in the fiber pathogenicity paradigm. This paradigm is a robust structure:toxicity model that identifies thin, long, biopersistent fibers as the ED for fiber-type pathogenic effects. It is likely that HARNs will in general conform to the paradigm and such an understanding of the features that make fibers pathogenic should enable us to design safer HARNs.
- 21Murphy, F.; Jacobsen, N. R.; Di Ianni, E.; Johnston, H.; Braakhuis, H.; Peijnenburg, W.; Oomen, A.; Fernandes, T.; Stone, V. Grouping MWCNTs Based on Their Similar Potential to Cause Pulmonary Hazard after Inhalation: A Case-Study. Part. Fibre Toxicol. 2022, 19 (1), 50, DOI: 10.1186/s12989-022-00487-621https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BB2MbgsVGrug%253D%253D&md5=0e563f91bff4793fa9590da60ba3344aGrouping MWCNTs based on their similar potential to cause pulmonary hazard after inhalation: a case-studyMurphy Fiona; Johnston Helinor; Fernandes Teresa; Stone Vicki; Jacobsen Nicklas Raun; Di Ianni Emilio; Braakhuis Hedwig; Peijnenburg Willie; Oomen Agnes; Peijnenburg WillieParticle and fibre toxicology (2022), 19 (1), 50 ISSN:.BACKGROUND: The EU-project GRACIOUS developed an Integrated Approach to Testing and Assessment (IATA) to support grouping high aspect ratio nanomaterials (HARNs) presenting a similar inhalation hazard. Application of grouping reduces the need to assess toxicity on a case-by-case basis and supports read-across of hazard data from substances that have the data required for risk assessment (source) to those that lack such data (target). The HARN IATA, based on the fibre paradigm for pathogenic fibres, facilitates structured data gathering to propose groups of similar HARN and to support read-across by prompting users to address relevant questions regarding HARN morphology, biopersistence and inflammatory potential. The IATA is structured in tiers, allowing grouping decisions to be made using simple in vitro or in silico methods in Tier1 progressing to in vivo approaches at the highest Tier3. Here we present a case-study testing the applicability of GRACIOUS IATA to form an evidence-based group of multiwalled carbon nanotubes (MWCNT) posing a similar predicted fibre-hazard, to support read-across and reduce the burden of toxicity testing. RESULTS: The case-study uses data on 15 different MWCNT, obtained from the published literature. By following the IATA, a group of 2 MWCNT was identified (NRCWE006 and NM-401) based on a high degree of similarity. A pairwise similarity assessment was subsequently conducted between the grouped MWCNT to evaluate the potential to conduct read-across and fill data gaps required for regulatory hazard assessment. The similarity assessment, based on expert judgement of Tier 1 assay results, predicts both MWCNT are likely to cause a similar acute in vivo hazard. This result supports the possibility for read-across of sub-chronic and chronic hazard endpoint data for lung fibrosis and carcinogenicity between the 2 grouped MWCNT. The implications of accepting the similarity assessment based on expert judgement of the MWCNT group are considered to stimulate future discussion on the level of similarity between group members considered sufficient to allow regulatory acceptance of a read-across argument. CONCLUSION: This proof-of-concept case-study demonstrates how a grouping hypothesis and IATA may be used to support a nuanced and evidence-based grouping of 'similar' MWCNT and the subsequent interpolation of data between group members to streamline the hazard assessment process.
- 22Murphy, F.; Dekkers, S.; Braakhuis, H.; Ma-Hock, L.; Johnston, H.; Janer, G.; di Cristo, L.; Sabella, S.; Jacobsen, N. R.; Oomen, A. G. An Integrated Approach to Testing and Assessment of High Aspect Ratio Nanomaterials and Its Application for Grouping Based on a Common Mesothelioma Hazard. NanoImpact 2021, 22, 100314, DOI: 10.1016/j.impact.2021.10031422https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB38XhtlSrsL%252FE&md5=0faa3b8f71ca2d66f3f101c659882507An integrated approach to testing and assessment of high aspect ratio nanomaterials and its application for grouping based on a common mesothelioma hazardMurphy, Fiona; Dekkers, Susan; Braakhuis, Hedwig; Ma-Hock, Lan; Johnston, Helinor; Janer, Gemma; di Cristo, Luisana; Sabella, Stefania; Jacobsen, Nicklas Raun; Oomen, Agnes G.; Haase, Andrea; Fernandes, Teresa; Stone, VickiNanoImpact (2021), 22 (), 100314CODEN: NANOPT; ISSN:2452-0748. (Elsevier B.V.)Here we describe the development of an Integrated Approach to Testing and Assessment (IATA) to support the grouping of different types (nanoforms; NFs) of High Aspect Ratio Nanomaterials (HARNs), based on their potential to cause mesothelioma. Hazards posed by the inhalation of HARNs are of particular concern as they exhibit phys. characteristics similar to pathogenic asbestos fibers. The approach for grouping HARNs presented here is part of a framework to provide guidance and tools to group similar NFs and aims to reduce the need to assess toxicity on a case-by-case basis. The approach to grouping is hypothesis-driven, in which the hypothesis is based on scientific evidence linking crit. physicochem. descriptors for NFs to defined fate/toxicokinetic and hazard outcomes. The HARN IATA prompts users to address relevant questions (at decision nodes; DNs) regarding the morphol., biopersistence and inflammatory potential of the HARNs under investigation to provide the necessary evidence to accept or reject the grouping hypothesis. Each DN in the IATA is addressed in a tiered manner, using data from simple in vitro or in silico methods in the lowest tier or from in vivo approaches in the highest tier. For these proposed methods we provide justification for the crit. descriptors and thresholds that allow grouping decisions to be made. Application of the IATA allows the user to selectively identify HARNs which may pose a mesothelioma hazard, as demonstrated through a literature-based case study. By promoting the use of alternative, non-rodent approaches such as in silico modeling, in vitro and cell-free tests in the initial tiers, the IATA testing strategy streamlines information gathering at all stages of innovation through to regulatory risk assessment while reducing the ethical, time and economic burden of testing.
- 23Nel, A. Carbon Nanotube Pathogenicity Conforms to a Unified Theory for Mesothelioma Causation by Elongate Materials and Fibers. Environ. Res. 2023, 230, 114580 DOI: 10.1016/j.envres.2022.11458023https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3sXmtVSjtbY%253D&md5=fcaba6897bffb8375fa6dff3e3a2bde7Carbon nanotube pathogenicity conforms to a unified theory for mesothelioma causation by elongate materials and fibersNel, AndreEnvironmental Research (2023), 230 (), 114580CODEN: ENVRAL; ISSN:0013-9351. (Elsevier Inc.)A review. The purpose of this review is to elucidate how dimensional and durability characteristics of high aspect ratio nanomaterials (HARN), including carbon nanotubes (CNT) and metal nanowires (MeNW), contribute to understanding the fiber pathogenicity paradigm (FPP), including by explaining the structure-activity relationships (SAR) of a diverse range of natural and synthetic elongate materials that may or may not contribute to mesothelioma development in the lung. While the FPP was originally developed to explain the crit. importance of asbestos and synthetic vitreous fiber length, width, aspect ratio and biopersistence in mesothelioma development, there are a vast no. of addnl. inhalable materials that need to be considered in terms of pathogenic features that may contribute to mesothelioma or lack thereof. Not only does the ability to exert more exact control over the length and biopersistence of HARNs confirm the tenets of the FPP, but could be studied by implementating more appropriate toxicol. tools for SAR anal. This includes experimentation with carefully assembled libraries of CNTs and MeNWs, helping to establish more precise dimensional features for interfering in lymphatic drainage from the parietal pleura, triggering of lysosomal damage, frustrated phagocytosis and generation of chronic inflammation. The evidence includes data that long and rigid, but not short and flexible multi-wall CNTs are capable of generating mesotheliomas in rodents based on an adverse outcome pathway requiring access to pleural cavity, obstruction of pleural stomata, chronic inflammation and transformation of mesothelial cells. In addn. to durability and dimensional characteristics, bending stiffness of CNTs is a crit. factor in detg. the shape and rigidity of pathogenic MWCNTs. While no evidence has been obtained in humans that CNT exposure leads to a mesothelioma outcome, it is important to monitor exposure levels and health effect impacts in workers to prevent adverse health outcomes in humans.
- 24Rodrigues, A. F.; Newman, L.; Jasim, D. A.; Vacchi, I. A.; Ménard-Moyon, C.; Crica, L. E.; Bianco, A.; Kostarelos, K.; Bussy, C. Immunological Impact of Graphene Oxide Sheets in the Abdominal Cavity Is Governed by Surface Reactivity. Arch. Toxicol. 2018, 92 (11), 3359– 3379, DOI: 10.1007/s00204-018-2303-z24https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1cXhvVSmsL%252FL&md5=e47ab5e6e62bd31b8e8e64fd9fd7c909Immunological impact of graphene oxide sheets in the abdominal cavity is governed by surface reactivityRodrigues, Artur Filipe; Newman, Leon; Jasim, Dhifaf A.; Vacchi, Isabella A.; Menard-Moyon, Cecilia; Crica, Livia E.; Bianco, Alberto; Kostarelos, Kostas; Bussy, CyrillArchives of Toxicology (2018), 92 (11), 3359-3379CODEN: ARTODN; ISSN:0340-5761. (Springer)Graphene oxide (GO) is an oxidised form of graphene that has attracted com. interest in multiple applications, including inks, printed electronics and spray coatings, which all raise health concerns due to potential creation of inhalable aerosols. Although a no. of studies have discussed the toxicity of GO sheets, the in vivo impact of their lateral dimensions is still not clear. To benchmark the outcomes, long and rigid multi-walled carbon nanotubes (MWCNTs) that were shown to be assocd. with asbestos-like pathogenicity on the mesothelium were also tested. Our aim was to assess whether lateral dimensions can be a predictor of inflammogenicity for GO sheets in a similar fashion as length is for MWCNTs. Such recruitment coincided with the greater ability of s-GO to interact in vivo with peritoneal macrophages and was assocd. with a greater surface reactivity in comparison to l-GO. In conclusion, large dimension was not a detg. factor of the immunol. impact of GO sheets after i.p. administration. On the other hand, surface reactivity and the ability of some smaller GO sheets to interact more readily with immune cells seem to be key parameters that can be tuned to improve the safety profile of GO. Overall, these findings are essential for a better understanding of the parameters governing GO toxicity and inflammation, and the rational design of safe GO-based formulations for various applications, including biomedicine.
- 25Rodrigues, A. F.; Newman, L.; Jasim, D.; Mukherjee, S. P.; Wang, J.; Vacchi, I. A.; Ménard-Moyon, C.; Bianco, A.; Fadeel, B.; Kostarelos, K. Size-Dependent Pulmonary Impact of Thin Graphene Oxide Sheets in Mice: Toward Safe-by-Design. Adv. Sci. 2020, 7 (12), 1903200 DOI: 10.1002/advs.20190320025https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXitVKhtbvK&md5=f16648d20bb53e8b539e8cca382ec6d2Size-Dependent Pulmonary Impact of Thin Graphene Oxide Sheets in Mice: Toward Safe-by-DesignRodrigues, Artur Filipe; Newman, Leon; Jasim, Dhifaf; Mukherjee, Sourav P.; Wang, Jun; Vacchi, Isabella A.; Menard-Moyon, Cecilia; Bianco, Alberto; Fadeel, Bengt; Kostarelos, Kostas; Bussy, CyrillAdvanced Science (Weinheim, Germany) (2020), 7 (12), 1903200CODEN: ASDCCF; ISSN:2198-3844. (Wiley-VCH Verlag GmbH & Co. KGaA)Safety assessment of graphene-based materials (GBMs) including graphene oxide (GO) is essential for their safe use across many sectors of society. In particular, the link between specific material properties and biol. effects needs to be further elucidated. Here, the effects of lateral dimensions of GO sheets in acute and chronic pulmonary responses after single intranasal instillation in mice are compared. Micrometer-sized GO induces stronger pulmonary inflammation than nanometer-sized GO, despite reduced translocation to the lungs. Genome-wide RNA sequencing also reveals distinct size-dependent effects of GO, in agreement with the histopathol. results. Although large GO, but not the smallest GO, triggers the formation of granulomas that persists for up to 90 days, no pulmonary fibrosis is obsd. These latter results can be partly explained by Raman imaging, which evidences the progressive biotransformation of GO into less graphitic structures. The findings demonstrate that lateral dimensions play a fundamental role in the pulmonary response to GO, and suggest that airborne exposure to micrometer-sized GO should be avoided in the prodn. plant or applications, where aerosolized dispersions are likely to occur. These results are important toward the implementation of a safer-by-design approach for GBM products and applications, for the benefit of workers and end-users.
- 26Loret, T.; Visani de Luna, L. A.; Fordham, A.; Arshad, A.; Barr, K.; Lozano, N.; Kostarelos, K.; Bussy, C. Innate but Not Adaptive Immunity Regulates Lung Recovery from Chronic Exposure to Graphene Oxide Nanosheets. Adv. Sci. 2022, 9, 2104559 DOI: 10.1002/advs.20210455926https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB38XhtVGis7jJ&md5=0e6623de2252bce8609db83148e7547aInnate but Not Adaptive Immunity Regulates Lung Recovery from Chronic Exposure to Graphene Oxide NanosheetsLoret, Thomas; de Luna, Luis Augusto Visani; Fordham, Alexander; Arshad, Atta; Barr, Katharine; Lozano, Neus; Kostarelos, Kostas; Bussy, CyrillAdvanced Science (Weinheim, Germany) (2022), 9 (11), 2104559CODEN: ASDCCF; ISSN:2198-3844. (Wiley-VCH Verlag GmbH & Co. KGaA)Graphene has drawn a lot of interest in the material community due to unique physicochem. properties. Owing to a high surface area to vol. ratio and free oxygen groups, the oxidized deriv., graphene oxide (GO) has promising potential as a drug delivery system. Here, the lung tolerability of two distinct GO varying in lateral dimensions is investigated, to reveal the most suitable candidate platform for pulmonary drug delivery. Following repeated chronic pulmonary exposure of mice to GO sheet suspensions, the innate and adaptive immune responses are studied. An acute and transient influx of neutrophils and eosinophils in the alveolar space, together with the replacement of alveolar macrophages by interstitial ones and a significant activation toward anti-inflammatory subsets, are found for both GO materials. Micrometric GO give rise to persistent multinucleated macrophages and granulomas. However, neither adaptive immune response nor lung tissue remodeling are induced after exposure to micrometric GO. Concurrently, milder effects and faster tissue recovery, both assocd. to a faster clearance from the respiratory tract, are found for nanometric GO, suggesting a greater lung tolerability. Taken together, these results highlight the importance of dimensions in the design of biocompatible 2D materials for pulmonary drug delivery system.
- 27Visani de Luna, L. A.; Loret, T.; Fordham, A.; Arshad, A.; Drummond, M.; Dodd, A.; Lozano, N.; Kostarelos, K.; Bussy, C. Lung Recovery from DNA Damage Induced by Graphene Oxide Is Dependent on Size, Dose and Inflammation Profile. Part. Fibre Toxicol. 2022, 19, 62, DOI: 10.1186/s12989-022-00502-wThere is no corresponding record for this reference.
- 28Smith, R. J.; King, P. J.; Lotya, M.; Wirtz, C.; Khan, U.; De, S.; O’Neill, A.; Duesberg, G. S.; Grunlan, J. C.; Moriarty, G. Large-Scale Exfoliation of Inorganic Layered Compounds in Aqueous Surfactant Solutions. Adv. Mater. 2011, 23 (34), 3944– 3948, DOI: 10.1002/adma.20110258428https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXpsFaisrg%253D&md5=ad837ed3dce21542d32ba74b7410603aLarge-Scale Exfoliation of Inorganic Layered Compounds in Aqueous Surfactant SolutionsSmith, Ronan J.; King, Paul J.; Lotya, Mustafa; Wirtz, Christian; Khan, Umar; De, Sukanta; O'Neill, Arlene; Duesberg, Georg S.; Grunlan, Jaime C.; Moriarty, Gregory; Chen, Jun; Wang, Jiazhao; Minett, Andrew I.; Nicolosi, Valeria; Coleman, Jonathan N.Advanced Materials (Weinheim, Germany) (2011), 23 (34), 3944-3948CODEN: ADVMEW; ISSN:0935-9648. (Wiley-VCH Verlag GmbH & Co. KGaA)We show a simple, large-scale method to exfoliate layered compds. such as BN, transition metal dichalcogenides, and transition metal oxides down to very thin platelets in water. The platelets are stabilized against reaggregation by a surfactant coating. This method is robust, can be carried out in ambient conditions, is scalable, and allows the prepn. of films, hybrids, and composites. We suggest that ionic surfactants are ideal stabilizers due to their van der Waals binding to the exfoliated nanosheets and subsequent electrostatic stabilization.
- 29Lago, E.; Toth, P. S.; Gentiluomo, S.; Thorat, S. B.; Pellegrini, V.; Bonaccorso, F. Dependence of the Polycarbonate Mechanical Performances on Boron Nitride Flakes Morphology. JPhys. Mater. 2021, 4 (4). 045002 DOI: 10.1088/2515-7639/ac0ac0 .29https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3MXislehsbzJ&md5=dff95ae94fee6d51d8b3be818e78f3cfDependence of the polycarbonate mechanical performances on boron nitride flakes morphologyLago, Emanuele; Toth, Peter S.; Gentiluomo, Silvia; Thorat, Sanjay B.; Pellegrini, Vittorio; Bonaccorso, FrancescoJPhys Materials (2021), 4 (4), 045002CODEN: JPMOC4; ISSN:2515-7639. (IOP Publishing Ltd.)A key requirement for the exploitation of two-dimensional (2D)-crystals in the field of composites relies on their large-scale prodn. In this respect, liq. phase exfoliation of layered-crystals is emerging as one of the most promising approaches for the scalable prodn. of high-quality 2D-crystals. However, the dependence of the 2D crystal flakes morphol., i.e. thickness and lateral size, on the mech. properties of the polymer composites is not fully understood yet. Herein, we tackle this issue by designing an environmentally friendly approach, based on the exfoliation of bulk hexagonal-boron nitride (h-BN), widely used as filler in polymer composites for its high intrinsic stiffness, i.e. approaching 1 TPa, in a water/surfactant soln. with controlled thickness and lateral size by using cascade ultra-centrifugation. Our approach allows us to obtain two populations of flakes with aspect ratio, i.e. lateral size over thickness, equal to 250 and 350, resp. The h-BN flakes with tuned aspect ratio are subsequently used as filler in a polycarbonate (PC) matrix by exploiting soln. blending in 1,3-dioxolane, a solvent with Hansen's soly. parameters matching the ones of h-BN, thus enhancing the dispersion of the filler inside the matrix, as evaluated by Raman mapping. We tested the composite mech. properties finding that flakes with higher aspect ratio show superior reinforcements in terms of both ultimate tensile strength and Young's modulus, compared with their lower aspect ratio counterparts. As example, at 0.1 wt% of loading, the difference in reinforcement in terms of Young's Modulus is of 56 MPa, being the increment, compared to pristine PC, of ~ 22% for composites produced with higher aspect ratio fillers, whereas it is instead of only ~ 17% for lower aspect ratio fillers.
- 30Huang, C.; Chen, C.; Ye, X.; Ye, W.; Hu, J.; Xu, C.; Qiu, X. Stable Colloidal Boron Nitride Nanosheet Dispersion and Its Potential Application in Catalysis. J. Mater. Chem. A 2013, 1 (39). 12192 DOI: 10.1039/c3ta12231j .30https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXhsVOgsL3I&md5=ddf40d62e4ca44c80bca0991c2ecfe45Stable colloidal boron nitride nanosheet dispersion and its potential application in catalysisHuang, Caijin; Chen, Cheng; Ye, Xinxin; Ye, Weiqing; Hu, Jinli; Xu, Chao; Qiu, XiaoqingJournal of Materials Chemistry A: Materials for Energy and Sustainability (2013), 1 (39), 12192-12197CODEN: JMCAET; ISSN:2050-7496. (Royal Society of Chemistry)Stable colloidal nanosheet dispersions of hexagonal boron nitride (h-BN) with high concn. have been prepd. in ethylene glycol using matching of the surface energies of h-BN and the surface tension of the solvent. Bulk h-BN was directly exfoliated and dispersed in ethylene glycol with the assistance of sonication to form stable h-BN nanosheets with a few layers. The stable colloidal h-BN nanosheets were good carriers to support and disperse noble metal nanoparticles such as Ag, Au, and Pt with high catalytic activity for the redn. of p-nitrophenol.
- 31Si, P. Z.; Zhang, M.; You, C. Y.; Geng, D. Y.; Du, J. H.; Zhao, X. G.; Ma, X. L.; Zhang, Z. D. Amorphous Boron Nanoparticles and BN Encapsulating Boron Nano-Peanuts Prepared by Arc-Decomposing Diborane and Nitriding. J. Mater. Sci. 2003, 38 (4), 689– 692, DOI: 10.1023/A:102183220925031https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD3sXit1GjsQ%253D%253D&md5=4a5526db33c7eff92012cb05fcf3ec9bAmorphous boron nanoparticles and BN encapsulating boron nano-peanuts prepared by arc-decomposing diborane and nitridingSi, P. Z.; Zhang, M.; You, C. Y.; Geng, D. Y.; Du, J. H.; Zhao, X. G.; Ma, X. L.; Zhang, Z. D.Journal of Materials Science (2003), 38 (4), 689-692CODEN: JMTSAS; ISSN:0022-2461. (Kluwer Academic Publishers)Amorphous boron nanoparticles were prepd. by arc-decompg. diborane, which had ideal morphologies in comparison with that of those fabricated by furnace or laser heating diborane. Peanut-shaped boron nitride encapsulating boron nanocapsules were fabricated by nitridation of amorphous boron nanoparticles. Unique core/void/shell structure of the nanocapsules was obsd. by a high-resoln. TEM. The mechanism of growing the BN nanocapsules by a catalyst-free process was distinctly different from the process of arc discharge or laser heating. The broadening of nonpolar intralayer Raman line of hexagonal BN at about 1370 cm-1 was obsd., which was attributed to the small crystal size of BN.
- 32Kurapati, R.; Backes, C.; Ménard-Moyon, C.; Coleman, J. N.; Bianco, A. White Graphene Undergoes Peroxidase Degradation. Angew. Chemie Int. Ed. 2016, 55 (18), 5506– 5511, DOI: 10.1002/anie.20160123832https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28XkvVChsb4%253D&md5=4cda956f69edbd641ef56712dd476255White Graphene undergoes Peroxidase DegradationKurapati, Rajendra; Backes, Claudia; Menard-Moyon, Cecilia; Coleman, Jonathan N.; Bianco, AlbertoAngewandte Chemie, International Edition (2016), 55 (18), 5506-5511CODEN: ACIEF5; ISSN:1433-7851. (Wiley-VCH Verlag GmbH & Co. KGaA)Hexagonal boron nitride (hBN) nanosheets are emerging as promising 2D materials for different types of applications. However, biodegrdn. of hBN materials is poorly explored owing to their high chem. inertness and strong oxidn. resistance. The assessment of oxidn./biodegrdn. of hBN is important in developing biomedical tools. Herein, we report the first study on the biodegradability of hBN nanosheets comparing the enzymic catalysis of two different peroxidases, horseradish peroxidase (HRP) and human myeloperoxidase (MPO), with the photo-Fenton (P.F.) reaction. The results show that degrdn. of hBN nanosheets is different to that of graphene and graphene oxide, since partial oxidn. was found using MPO after 35 h, while HRP failed to degrade hBN up to 60 days. Nearly complete oxidn./degrdn. was occurred by P. F. reaction in 100 h. These results are helpful in designing advanced conjugates for biomedical uses of hBN.
- 33Saber, A. T.; Jacobsen, N. R.; Jackson, P.; Poulsen, S. S.; Kyjovska, Z. O.; Halappanavar, S.; Yauk, C. L.; Wallin, H.; Vogel, U. Particle-Induced Pulmonary Acute Phase Response May Be the Causal Link between Particle Inhalation and Cardiovascular Disease. Wiley Interdisciplinary Reviews: Nanomedicine and Nanobiotechnology. 2014, 6, 517– 531, DOI: 10.1002/wnan.127933https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXhslCqtrrJ&md5=539e8a0089973ad44ab30ebb9049cae5Particle-induced pulmonary acute phase response may be the causal link between particle inhalation and cardiovascular diseaseSaber, Anne T.; Jacobsen, Nicklas R.; Jackson, Petra; Poulsen, Sarah Sos; Kyjovska, Zdenka O.; Halappanavar, Sabina; Yauk, Carole L.; Wallin, Hakan; Vogel, UllaWiley Interdisciplinary Reviews: Nanomedicine and Nanobiotechnology (2014), 6 (6), 517-531CODEN: WIRNBH; ISSN:1939-0041. (Wiley-Blackwell)Inhalation of ambient and workplace particulate air pollution is assocd. with increased risk of cardiovascular disease. One proposed mechanism for this assocn. is that pulmonary inflammation induces a hepatic acute phase response, which increases risk of cardiovascular disease. Induction of the acute phase response is intimately linked to risk of cardiovascular disease as shown in both epidemiol. and animal studies. Indeed, blood levels of acute phase proteins, such as C-reactive protein and serum amyloid A, are independent predictors of risk of cardiovascular disease in prospective epidemiol. studies. In this review, we present and review emerging evidence that inhalation of particles (e.g., air diesel exhaust particles and nanoparticles) induces a pulmonary acute phase response, and propose that this induction constitutes the causal link between particle inhalation and risk of cardiovascular disease. Increased levels of acute phase mRNA and proteins in lung tissues, bronchoalveolar lavage fluid and plasma clearly indicate pulmonary acute phase response following pulmonary deposition of different kinds of particles including diesel exhaust particles, nanoparticles, and carbon nanotubes. The pulmonary acute phase response is dose-dependent and long lasting. Conversely, the hepatic acute phase response is reduced relative to lung or entirely absent. We also provide evidence that pulmonary inflammation, as measured by neutrophil influx, is a predictor of the acute phase response and that the total surface area of deposited particles correlates with the pulmonary acute phase response. We discuss the implications of these findings in relation to occupational exposure to nanoparticles.
- 34Hadrup, N.; Zhernovkov, V.; Jacobsen, N. R.; Voss, C.; Strunz, M.; Ansari, M.; Schiller, H. B.; Halappanavar, S.; Poulsen, S. S.; Kholodenko, B. Acute Phase Response as a Biological Mechanism-of-Action of (Nano)Particle-Induced Cardiovascular Disease. Small. 2020, DOI: 10.1002/smll.201907476There is no corresponding record for this reference.
- 35Loret, T.; de Luna, L. A. V.; Lucherelli, M. A.; Fordham, A.; Lozano, N.; Bianco, A.; Kostarelos, K.; Bussy, C. Lung Persistence, Biodegradation, and Elimination of Graphene-Based Materials Are Predominantly Size-Dependent and Mediated by Alveolar Phagocytes. Small 2023, 19, 2301201 DOI: 10.1002/smll.20230120135https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3sXhtFGnur7O&md5=6b4e8ece4eabf5bf0be030ab4a840359Lung Persistence, Biodegradation, and Elimination of Graphene-Based Materials are Predominantly Size-Dependent and Mediated by Alveolar PhagocytesLoret, Thomas; de Luna, Luis Augusto Visani; Lucherelli, Matteo Andrea; Fordham, Alexander; Lozano, Neus; Bianco, Alberto; Kostarelos, Kostas; Bussy, CyrillSmall (2023), 19 (39), 2301201CODEN: SMALBC; ISSN:1613-6810. (Wiley-VCH Verlag GmbH & Co. KGaA)Graphene-based materials (GBMs) have promising applications in various sectors, including pulmonary nanomedicine. Nevertheless, the influence of GBM physicochem. characteristics on their fate and impact in lung has not been thoroughly addressed. To fill this gap, the biol. response, distribution, and bio-persistence of four different GBMs in mouse lungs up to 28 days after single oropharyngeal aspiration are investigated. None of the GBMs, varying in size (large vs. small) and carbon to oxygen ratio as well as thickness (few-layers graphene (FLG) vs. thin graphene oxide (GO)), induce a strong pulmonary immune response. However, recruited neutrophils internalize nanosheets better and degrade GBMs faster than macrophages, revealing their crucial role in the elimination of small GBMs. In contrast, large GO sheets induce more damages due to a hindered degrdn. and long-term persistence in macrophages. Overall, small dimensions appear to be a leading feature in the design of safe GBM pulmonary nanovectors due to an enhanced degrdn. in phagocytes and a faster clearance from the lungs for small GBMs. Thickness also plays an important role, since decreased material loading in alveolar phagocytes and faster elimination are found for FLGs compared to thinner GOs. These results are important for designing safer-by-design GBMs for biomedical application.
- 36Poland, C. A.; Duffin, R.; Kinloch, I. A.; Maynard, A.; Wallace, W. A. H.; Seaton, A.; Stone, V.; Brown, S.; Macnee, W.; Donaldson, K. Carbon Nanotubes Introduced into the Abdominal Cavity of Mice Show Asbestos-like Pathogenicity in a Pilot Study. Nat. Nanotechnol. 2008, 3 (7), 423– 428, DOI: 10.1038/nnano.2008.11136https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1cXotFehs7o%253D&md5=54ae8b1abbe311ade69bb8255891b407Carbon nanotubes introduced into the abdominal cavity of mice show asbestos-like pathogenicity in a pilot studyPoland, Craig A.; Duffin, Rodger; Kinloch, Ian; Maynard, Andrew; Wallace, William A. H.; Seaton, Anthony; Stone, Vicki; Brown, Simon; MacNee, William; Donaldson, KenNature Nanotechnology (2008), 3 (7), 423-428CODEN: NNAABX; ISSN:1748-3387. (Nature Publishing Group)Carbon nanotubes have distinctive characteristics, but their needle-like fiber shape has been compared to asbestos, raising concerns that widespread use of carbon nanotubes may lead to mesothelioma, cancer of the lining of the lungs caused by exposure to asbestos. Exposing the mesothelial lining of the body cavity of mice, as a surrogate for the mesothelial lining of the chest cavity, to long multiwalled carbon nanotubes results in asbestos-like, length-dependent, pathogenic behavior. This includes inflammation and the formation of lesions known as granulomas. This is of considerable importance, because research and business communities continue to invest heavily in carbon nanotubes for a wide range of products under the assumption that they are no more hazardous than graphite. The authors' results suggest the need for further research and great caution before introducing such products into the market if long-term harm is to be avoided. A pilot study in a small no. of mice shows that long multiwalled carbon nanotubes introduced into the abdominal cavity can cause asbestos-like pathogenic behavior. The results suggest the need for further research and caution before introducing nanotube products into the market.
- 37Christophersen, D. V.; Møller, P.; Thomsen, M. B.; Lykkesfeldt, J.; Loft, S.; Wallin, H.; Vogel, U.; Jacobsen, N. R. Accelerated Atherosclerosis Caused by Serum Amyloid A Response in Lungs of ApoE–/– Mice. FASEB J. 2021, 35 (3), e21307, DOI: 10.1096/fj.202002017R37https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3MXmt1elsLY%253D&md5=64a14843ddbceb90956c025b50131ba0Accelerated atherosclerosis caused by serum amyloid A response in lungs of ApoE-/- miceChristophersen, Daniel Vest; Moeller, Peter; Thomsen, Morten Baekgaard; Lykkesfeldt, Jens; Loft, Steffen; Wallin, Hakan; Vogel, Ulla; Jacobsen, Nicklas RaunFASEB Journal (2021), 35 (3), e21307CODEN: FAJOEC; ISSN:1530-6860. (John Wiley & Sons, Inc.)Airway exposure to eg particulate matter is assocd. with cardiovascular disease including atherosclerosis. Acute phase genes, esp. Serum Amyloid A3 (Saa3), are highly expressed in the lung following pulmonary exposure to particles. We aimed to investigate whether the human acute phase protein SAA (a homolog to mouse SAA3) accelerated atherosclerotic plaque progression in Apolipoprotein E knockout (ApoE-/-) mice. Mice were intratracheally (i.t.) instilled with vehicle (phosphate buffered saline) or 2μg human SAA once a week for 10 wk. Plaque progression was assessed in the aorta using noninvasive ultrasound imaging of the aorta arch as well as by en face anal. Addnl., lipid peroxidn., SAA3, and cholesterol were measured in plasma, inflammation was detd. in lung, and mRNA levels of the acute phase genes Saa1 and Saa3 were measured in the liver and lung, resp. Repeated i.t. instillation with SAA caused a significant progression in the atherosclerotic plaques in the aorta (1.5-fold). Concomitantly, SAA caused a statistically significant increase in neutrophils in bronchoalveolar lavage fluid (625-fold), in pulmonary Saa3 (196-fold), in systemic SAA3 (1.8-fold) and malondialdehyde levels (1.14-fold), indicating acute phase response (APR), inflammation and oxidative stress. Finally, pulmonary exposure to SAA significantly decreased the plasma levels of very low-d. lipoproteins - low-d. lipoproteins and total cholesterol, possibly due to lipids being sequestered in macrophages or foam cells in the arterial wall. Combined these results indicate the importance of the pulmonary APR and SAA3 for plaque progression.
- 38Gutierrez, C. T.; Loizides, C.; Hafez, I.; Brostrøm, A.; Wolff, H.; Szarek, J.; Berthing, T.; Mortensen, A.; Jensen, K. A.; Roursgaard, M. Acute Phase Response Following Pulmonary Exposure to Soluble and Insoluble Metal Oxide Nanomaterials in Mice. Part. Fibre Toxicol. 2023, 20 (1), 4, DOI: 10.1186/s12989-023-00514-038https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3sXitFSmsrg%253D&md5=c2bf4e3a4d4094ca47d19efcffc63d31Acute phase response following pulmonary exposure to soluble and insoluble metal oxide nanomaterials in miceGutierrez, Claudia Torero; Loizides, Charis; Hafez, Iosif; Brostroem, Anders; Wolff, Henrik; Szarek, Jozef; Berthing, Trine; Mortensen, Alicja; Jensen, Keld Alstrup; Roursgaard, Martin; Saber, Anne Thoustrup; Moeller, Peter; Biskos, George; Vogel, UllaParticle and Fibre Toxicology (2023), 20 (1), 4CODEN: PFTABQ; ISSN:1743-8977. (BioMed Central Ltd.)Acute phase response (APR) is characterized by a change in concn. of different proteins, including C-reactive protein and serum amyloid A (SAA) that can be linked to both exposure to metal oxide nanomaterials and risk of cardiovascular diseases. In this study, we intratracheally exposed mice to ZnO, CuO, Al2O3, SnO2 and TiO2 and carbon black (Printex 90) nanomaterials with a wide range in phagolysosomal soly. We subsequently assessed neutrophil nos., protein and lactate dehydrogenase activity in bronchoalveolar lavage fluid, Saa3 and Saa1 mRNA levels in lung and liver tissue, resp., and SAA3 and SAA1/2 in plasma. Endpoints were analyzed 1 and 28 days after exposure, including histopathol. of lung and liver tissues. All nanomaterials induced pulmonary inflammation after 1 day, and exposure to ZnO, CuO, SnO2, TiO2 and Printex 90 increased Saa3 mRNA levels in lungs and Saa1 mRNA levels in liver. Addnl., CuO, SnO2, TiO2 and Printex 90 increased plasma levels of SAA3 and SAA1/2. Acute phase response was predicted by deposited surface area for insol. metal oxides, 1 and 28 days post-exposure. Sol. and insol. metal oxides induced dose-dependent APR with different time dependency. Neutrophil influx, Saa3 mRNA levels in lung tissue and plasma SAA3 levels correlated across all studied nanomaterials, suggesting that these endpoints can be used as biomarkers of acute phase response and cardiovascular disease risk following exposure to sol. and insol. particles.
- 39Fadeel, B.; Bussy, C.; Merino, S.; Vázquez, E.; Flahaut, E.; Mouchet, F.; Evariste, L.; Gauthier, L.; Koivisto, A. J.; Vogel, U. Safety Assessment of Graphene-Based Materials: Focus on Human Health and the Environment. ACS Nano 2018, 12 (11), 10582– 10620, DOI: 10.1021/acsnano.8b0475839https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1cXitVyju7nN&md5=f276495b7b3b777acedf279460618b25Safety Assessment of Graphene-Based Materials: Focus on Human Health and the EnvironmentFadeel, Bengt; Bussy, Cyrill; Merino, Sonia; Vazquez, Ester; Flahaut, Emmanuel; Mouchet, Florence; Evariste, Lauris; Gauthier, Laury; Koivisto, Antti J.; Vogel, Ulla; Martin, Cristina; Delogu, Lucia G.; Buerki-Thurnherr, Tina; Wick, Peter; Beloin-Saint-Pierre, Didier; Hischier, Roland; Pelin, Marco; Candotto Carniel, Fabio; Tretiach, Mauro; Cesca, Fabrizia; Benfenati, Fabio; Scaini, Denis; Ballerini, Laura; Kostarelos, Kostas; Prato, Maurizio; Bianco, AlbertoACS Nano (2018), 12 (11), 10582-10620CODEN: ANCAC3; ISSN:1936-0851. (American Chemical Society)A review. Graphene and its derivs. are heralded as "miracle" materials with manifold applications in different sectors of society from electronics to energy storage to medicine. The increasing exploitation of graphene-based materials (GBMs) necessitates a comprehensive evaluation of the potential impact of these materials on human health and the environment. Here, we discuss synthesis and characterization of GBMs as well as human and environmental hazard assessment of GBMs using in vitro and in vivo model systems with the aim to understand the properties that underlie the biol. effects of these materials; not all GBMs are alike, and it is essential that we disentangle the structure-activity relationships for this class of materials.
- 40Chortarea, S.; Kuru, O. C.; Netkueakul, W.; Pelin, M.; Keshavan, S.; Song, Z.; Ma, B.; Gómes, J.; Abalos, E. V.; Luna, L. A. V. de Hazard Assessment of Abraded Thermoplastic Composites Reinforced with Reduced Graphene Oxide. J. Hazard. Mater. 2022, 435, 129053 DOI: 10.1016/j.jhazmat.2022.12905340https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB38Xht1GjtLbO&md5=c6d41b6c20f872a84d69764a659ca81cHazard assessment of abraded thermoplastic composites reinforced with reduced graphene oxideChortarea, Savvina; Kuru, Ogul Can; Netkueakul, Woranan; Pelin, Marco; Keshavan, Sandeep; Song, Zhengmei; Ma, Baojin; Gomes, Julio; Abalos, Elvira Villaro; Luna, Luis Augusto Visani de; Loret, Thomas; Fordham, Alexander; Drummond, Matthew; Kontis, Nikolaos; Anagnostopoulos, George; Paterakis, George; Cataldi, Pietro; Tubaro, Aurelia; Galiotis, Costas; Kinloch, Ian; Fadeel, Bengt; Bussy, Cyrill; Kostarelos, Kostas; Buerki-Thurnherr, Tina; Prato, Maurizio; Bianco, Alberto; Wick, PeterJournal of Hazardous Materials (2022), 435 (), 129053CODEN: JHMAD9; ISSN:0304-3894. (Elsevier B.V.)Graphene-related materials (GRMs) are subject to intensive investigations and considerable progress has been made in recent years in terms of safety assessment. However, limited information is available concerning the hazard potential of GRM-contg. products such as graphene-reinforced composites. In the present study, we conducted a comprehensive investigation of the potential biol. effects of particles released through an abrasion process from reduced graphene oxide (rGO)-reinforced composites of polyamide 6 (PA6), a widely used engineered thermoplastic polymer, in comparison to as-produced rGO. First, a panel of well-established in vitro models, representative of the immune system and possible target organs such as the lungs, the gut, and the skin, was applied. Limited responses to PA6-rGO exposure were found in the different in vitro models. Only as-produced rGO induced substantial adverse effects, in particular in macrophages. Since inhalation of airborne materials is a key occupational concern, we then sought to test whether the in vitro responses noted for these materials would translate into adverse effects in vivo. To this end, the response at 1, 7 and 28 days after a single pulmonary exposure was evaluated in mice. In agreement with the in vitro data, PA6-rGO induced a modest and transient pulmonary inflammation, resolved by day 28. In contrast, rGO induced a longer-lasting, albeit moderate inflammation that did not lead to tissue remodeling within 28 days. Taken together, the present study suggests a negligible impact on human health under acute exposure conditions of GRM fillers such as rGO when released from composites at doses expected at the workplace.
- 41Schinwald, A.; Murphy, F. A.; Jones, A.; MacNee, W.; Donaldson, K. Graphene-Based Nanoplatelets: A New Risk to the Respiratory System as a Consequence of Their Unusual Aerodynamic Properties. ACS Nano 2012, 6, 736– 746, DOI: 10.1021/nn204229f41https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXhs1GrurnP&md5=d6893da59ca929cc9cd61bad2a6a5d24Graphene-Based Nanoplatelets: A New Risk to the Respiratory System as a Consequence of Their Unusual Aerodynamic PropertiesSchinwald, Anja; Murphy, Fiona A.; Jones, Alan; MacNee, William; Donaldson, KenACS Nano (2012), 6 (1), 736-746CODEN: ANCAC3; ISSN:1936-0851. (American Chemical Society)Graphene is a new nanomaterial with unusual and useful phys. and chem. properties. However, in the form of nanoplatelets this new, emerging material could pose unusual risks to the respiratory system after inhalation exposure. The graphene-based nanoplatelets used in this study are com. available and consist of several sheets of graphene (few-layer graphene). We first derived the respirability of graphene nanoplatelets (GP) from the basic principles of the aerodynamic behavior of plate-shaped particles which allowed us to calc. their aerodynamic diam. This showed that the nanoplatelets, which were up to 25 μm in diam., were respirable and so would deposit beyond the ciliated airways following inhalation. We therefore utilized models of pharyngeal aspiration and direct intrapleural installation of GP, as well as an in vitro model, to assess their inflammatory potential. These large but respirable GP were inflammogenic in both the lung and the pleural space. MIP-1α, MCP-1, MIP-2, IL-8, and IL-1β expression in the BAL, the pleural lavage, and cell culture supernatant from THP-1 macrophages were increased with GP exposure compared to controls but not with nanoparticulate carbon black (CB). In vitro, macrophages exposed to GP showed expression of IL-1β. This study highlights the importance of nanoplatelet form as a driver for in vivo and in vitro inflammogenicity by virtue of their respirable aerodynamic diam., despite a considerable 2-dimensional size which leads to frustrated phagocytosis when they deposit in the distal lungs and macrophages attempt to phagocytose them. Our data suggest that nanoplatelets pose a novel nanohazard and structure-toxicity relationship in nanoparticle toxicol.
- 42Mao, L.; Hu, M.; Pan, B.; Xie, Y.; Petersen, E. J. Biodistribution and Toxicity of Radio-Labeled Few Layer Graphene in Mice after Intratracheal Instillation. Part. Fibre Toxicol. 2015, 13 (1), 7, DOI: 10.1186/s12989-016-0120-1There is no corresponding record for this reference.
- 43Park, E. J.; Lee, G. H.; Han, B. S.; Lee, B. S.; Lee, S.; Cho, M. H.; Kim, J. H.; Kim, D. W. Toxic Response of Graphene Nanoplatelets in Vivo and in Vitro. Arch. Toxicol. 2015, 89, 1557, DOI: 10.1007/s00204-014-1303-x43https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXhtVOns7jE&md5=6d48dfebf8a4527c2c11e8ad49b82ecdToxic response of graphene nanoplatelets in vivo and in vitroPark, Eun-Jung; Lee, Gwang-Hee; Han, Beom Seok; Lee, Byoung-Seok; Lee, Somin; Cho, Myung-Haing; Kim, Jae-Ho; Kim, Dong-WanArchives of Toxicology (2015), 89 (9), 1557-1568CODEN: ARTODN; ISSN:0340-5761. (Springer)With the development of nanotechnol., myriad types of novel materials have been discovered at the nanoscale, among which the most interesting material is graphene. However, the toxicity data available on graphene are extremely limited. In this study, we explored toxic response of com. available graphene nanoplatelets (GNPs) in vivo and in vitro. The GNPs used in this study had a high surface area and feature considerably few defects. In mice, GNPs (2.5 and 5 mg/kg) remained in the lung until 28 days after a single instillation, and the secretion of inflammatory cytokines reached the maximal level at Day 14 and then decreased over time. In vitro study using BEAS-2B cells, a human bronchial epithelial cell line, GNPs located within autophagosome-like vacuoles 24 h after exposure. The GNPs (2.5, 5, 10, and 20 μg/mL) also dose-dependently reduced cell viability, which was accompanied by an increase in the portion of cells in the subG1 and S phases. Moreover, the GNPs down-regulated the generation of reactive oxygen species, suppressed ATP prodn., caused mitochondria damage, and elevated the levels of autophagy-related proteins. Based on these results, we suggest that GNPs provoked a subchronic inflammatory response in mice and that GNPs induced autophagy accompanying apoptosis via mitochondria damage in vitro.
- 44Schinwald, A.; Murphy, F. A.; Askounis, A.; Koutsos, V.; Sefiane, K.; Donaldson, K.; Campbell, C. J. Minimal Oxidation and Inflammogenicity of Pristine Graphene with Residence in the Lung. Nanotoxicology 2014, 8, 824– 832, DOI: 10.3109/17435390.2013.83150244https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXhvFemtbfE&md5=b92ca597d53c67224de3562203d26575Minimal oxidation and inflammogenicity of pristine graphene with residence in the lungSchinwald, Anja; Murphy, Fiona; Askounis, Alexandros; Koutsos, Vasileios; Sefiane, Khellil; Donaldson, Ken; Campbell, Colin J.Nanotoxicology (2014), 8 (8), 824-832CODEN: NANOGK; ISSN:1743-5404. (Informa Healthcare)Two-dimensional graphitic carbon, graphene, is a new form of nanomaterial with great potential in a wide variety of applications. It is therefore crucial to investigate the behavior of graphene in biol. systems to assess potential adverse effects that might follow from inhalation exposure. In this study we focussed on medium-term effects of graphene in lung tissue by investigating the pulmonary inflammation 6 wk after pharyngeal aspiration of unoxidised multilayered graphene platelets (GPs) in mice and assessed their biopersistence in the lung tissue using Raman spectroscopy. Addnl., GP degrdn. in vitro was examd. after horseradish peroxidase (HRP) treatment up to 1 wk. Building on our previous report showing acute inflammation in mice lungs at 1 day, pristine GP showed minimal inflammation in mouse lungs after 6 wk even though no degrdn. of GP in lung tissue was obsd. and large deposits of GP were evident in the lungs. Raman anal. of GP in tissue sections showed minimal oxidn., and in vitro examns. of enzymic oxidn. of GP via HRP and H2O2 showed only slight increases in ID/IG ratio and the appearance of the Raman D' band at 1620 cm-1 (surrogates of graphene oxidn.). Our results showing non-inflammogenicity at medium time points have important implications in the hazard identification of GPs following inhalation exposure and for their use in biomedical applications. Addnl., the biopersistence of pristine GP in vivo with no assocd. inflammation could open the way to applications in tissue engineering and drug delivery.
- 45Shin, J. H.; Han, S. G.; Kim, J. K.; Kim, B. W.; Hwang, J. H.; Lee, J. S.; Lee, J. H.; Baek, J. E.; Kim, T. G.; Kim, K. S. 5-Day Repeated Inhalation and 28-Day Post-Exposure Study of Graphene. Nanotoxicology 2015, 9 (8), 1023– 1031, DOI: 10.3109/17435390.2014.99830645https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXhvVWqtr%252FI&md5=4483282f44e912e3c35fcf8d255dff365-Day repeated inhalation and 28-day post-exposure study of grapheneShin, Jae Hoon; Han, Sung Gu; Kim, Jin Kwon; Kim, Boo Wook; Hwang, Joo Hwan; Lee, Jong Seong; Lee, Ji Hyun; Baek, Jin Ee; Kim, Tae Gyu; Kim, Keun Soo; Lee, Heon Sang; Song, Nam Woong; Ahn, Kangho; Yu, Il JeNanotoxicology (2015), 9 (8), 1023-1031CODEN: NANOGK; ISSN:1743-5404. (Taylor & Francis Ltd.)Graphene has recently been attracting increasing attention due to its unique electronic and chem. properties and many potential applications in such fields as semiconductors, energy storage, flexible electronics, biosensors and medical imaging. However, the toxicity of graphene in the case of human exposure has not yet been clarified. Thus, a 5-day repeated inhalation toxicity study of graphene was conducted using a nose-only inhalation system for male Sprague-Dawley rats. A total of three groups (20 rats per group) were compared: (1) control (ambient air), (2) low concn. (0.68 ± 0.14 mg/m3 graphene) and (3) high concn. (3.86 ± 0.94 mg/m3 graphene). The rats were exposed to graphene for 6 h/day for 5 days, followed by recovery for 1, 3, 7 or 28 days. The bioaccumulation and macrophage ingestion of the graphene were evaluated in the rat lungs. The exposure to graphene did not change the body wts. or organ wts. of the rats after the 5-day exposure and during the recovery period. No statistically significant difference was obsd. in the levels of lactate dehydrogenase, protein and albumin between the exposed and control groups. However, graphene ingestion by alveolar macrophages was obsd. in the exposed groups. Therefore, these results suggest that the 5-day repeated exposure to graphene only had a minimal toxic effect at the concns. and time points used in this study.
- 46Kim, J. K.; Shin, J. H.; Lee, J. S.; Hwang, J. H.; Lee, J. H.; Baek, J. E.; Kim, T. G.; Kim, B. W.; Kim, J. S.; Lee, G. H. 28-Day Inhalation Toxicity of Graphene Nanoplatelets in Sprague-Dawley Rats. Nanotoxicology 2016, 10 (7), 891– 901, DOI: 10.3109/17435390.2015.113386546https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28XisFGktrY%253D&md5=459f057b8d84c0771394c3d95247b14628-Day inhalation toxicity of graphene nanoplatelets in Sprague-Dawley ratsKim, Jin Kwon; Shin, Jae Hoon; Lee, Jong Seong; Hwang, Joo Hwan; Lee, Ji Hyun; Baek, Jin Ee; Kim, Tae Gyu; Kim, Boo Wook; Kim, Jin Sik; Lee, Gun Ho; Ahn, Kangho; Han, Sung Gu; Bello, Dhimiter; Yu, Il JeNanotoxicology (2016), 10 (7), 891-901CODEN: NANOGK; ISSN:1743-5404. (Taylor & Francis Ltd.)Graphene, a two-dimensional engineered nanomaterial, is now being used in many applications, such as electronics, biol. engineering, filtration, lightwt. and strong nanocomposite materials, and energy storage. However, there is a lack of information on the potential health effects of graphene in humans based on inhalation, the primary engineered nanomaterial exposure pathway in workplaces. Thus, an inhalation toxicol. study of graphene was conducted using a nose-only inhalation system for 28 days (6 h/day and 5 days/wk) with male Sprague-Dawley rats that were then allowed to recover for 1-, 28-, and 90-day post-exposure period. Animals were sepd. into 4 groups (control, low, moderate, and high) with 15 male rats (5 rats per time point) in each group. The measured mass concns. for the low, moderate, and high exposure groups were 0.12, 0.47, and 1.88 mg/m3, resp., very close to target concns. of 0.125, 0.5, and 2 mg/m3. Airborne graphene exposure was monitored using several real-time instrumentation over 10 nm to 20 μm for size distribution and no. concn. The total and respirable elemental carbon concns. were also measured using filter sampling. Graphene in the air and biol. media was traced using transmission electron microscopy. In addn. to mortality and clin. observations, the body wts. and food consumption were recorded weekly. At the end of the study, the rats were subjected to a full necropsy, blood samples were collected for blood biochem. tests, and the organ wts. were measured. No dose-dependent effects were recorded for the body wts., organ wts., bronchoalveolar lavage fluid inflammatory markers, and blood biochem. parameters at 1-day post-exposure and 28-day post-exposure. The inhaled graphenes were mostly ingested by macrophages. No distinct lung pathol. was obsd. at the 1-, 28- and 90-day post-exposure. The inhaled graphene was translocated to lung lymph nodes. The results of this 28-day graphene inhalation study suggest low toxicity and a NOAEL of no less than 1.88 mg/m3.
- 47Duch, M. C.; Budinger, G. R. S.; Liang, Y. T.; Soberanes, S.; Urich, D.; Chiarella, S. E.; Campochiaro, L. A.; Gonzalez, A.; Chandel, N. S.; Hersam, M. C. Minimizing Oxidation and Stable Nanoscale Dispersion Improves the Biocompatibility of Graphene in the Lung. Nano Lett. 2011, 11 (12), 5201– 5207, DOI: 10.1021/nl202515a47https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC38%252Fmt1ersw%253D%253D&md5=2901611a7f1af578ef7f0160bd2ee63dMinimizing oxidation and stable nanoscale dispersion improves the biocompatibility of graphene in the lungDuch Matthew C; Budinger G R Scott; Liang Yu Teng; Soberanes Saul; Urich Daniela; Chiarella Sergio E; Campochiaro Laura A; Gonzalez Angel; Chandel Navdeep S; Hersam Mark C; Mutlu Gokhan MNano letters (2011), 11 (12), 5201-7 ISSN:.To facilitate the proposed use of graphene and its derivative graphene oxide (GO) in widespread applications, we explored strategies that improve the biocompatibility of graphene nanomaterials in the lung. In particular, solutions of aggregated graphene, Pluronic dispersed graphene, and GO were administered directly into the lungs of mice. The introduction of GO resulted in severe and persistent lung injury. Furthermore, in cells GO increased the rate of mitochondrial respiration and the generation of reactive oxygen species, activating inflammatory and apoptotic pathways. In contrast, this toxicity was significantly reduced in the case of pristine graphene after liquid phase exfoliation and was further minimized when the unoxidized graphene was well-dispersed with the block copolymer Pluronic. Our results demonstrate that the covalent oxidation of graphene is a major contributor to its pulmonary toxicity and suggest that dispersion of pristine graphene in Pluronic provides a pathway for the safe handling and potential biomedical application of two-dimensional carbon nanomaterials.
- 48Li, R.; Guiney, L. M.; Chang, C. H.; Mansukhani, N. D.; Ji, Z.; Wang, X.; Liao, Y.-P. P.; Jiang, W.; Sun, B.; Hersam, M. C. Surface Oxidation of Graphene Oxide Determines Membrane Damage, Lipid Peroxidation, and Cytotoxicity in Macrophages in a Pulmonary Toxicity Model. ACS Nano 2018, 12 (2), 1390– 1402, DOI: 10.1021/acsnano.7b0773748https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1cXnvVCktw%253D%253D&md5=250124aed2894ca31da55bcaa2d3ce57Surface Oxidation of Graphene Oxide Determines Membrane Damage, Lipid Peroxidation, and Cytotoxicity in Macrophages in a Pulmonary Toxicity ModelLi, Ruibin; Guiney, Linda M.; Chang, Chong Hyun; Mansukhani, Nikhita D.; Ji, Zhaoxia; Wang, Xiang; Liao, Yu-Pei; Jiang, Wen; Sun, Bingbing; Hersam, Mark C.; Nel, Andre E.; Xia, TianACS Nano (2018), 12 (2), 1390-1402CODEN: ANCAC3; ISSN:1936-0851. (American Chemical Society)While two-dimensional graphene oxide (GO) is used increasingly in biomedical applications, there is uncertainty on how specific physicochem. properties relate to biocompatibility in mammalian systems. Although properties such as lateral size and the colloidal properties of the nanosheets are important, the specific material properties that we address here is the oxidn. state and reactive surface groups on the planar surface. In this study, we used a GO library, comprising pristine, reduced (rGO), and hydrated GO (hGO), in which quant. assessment of the hydroxyl, carboxyl, epoxy, and carbon radical contents was used to study the impact on epithelial cells and macrophages, as well as in the murine lung. Strikingly, we obsd. that hGO, which exhibits the highest carbon radical d., was responsible for the generation of cell death in THP-1 and BEAS-2B cells as a consequence of lipid peroxidn. of the surface membrane, membrane lysis, and cell death. In contrast, pristine GO had lesser effects, while rGO showed extensive cellular uptake with minimal effects on viability. In order to see how these in vitro effects relate to adverse outcomes in the lung, mice were exposed to GOs by oropharyngeal aspiration. Animal sacrifice after 40 h demonstrated that hGO was more prone than other materials to generate acute lung inflammation, accompanied by the highest lipid peroxidn. in alveolar macrophages, cytokine prodn. (LIX, MCP-1), and LDH release in bronchoalveolar lavage fluid. Pristine GO showed less toxicity, whereas rGO had minimal effects. We demonstrate that the surface oxidn. state and carbon radical content play major roles in the induction of toxicity by GO in mammalian cells and the lung.
- 49Bengtson, S.; Knudsen, K. B.; Kyjovska, Z. O.; Berthing, T.; Skaug, V.; Levin, M.; Koponen, I. K.; Shivayogimath, A.; Booth, T. J.; Alonso, B. Differences in Inflammation and Acute Phase Response but Similar Genotoxicity in Mice Following Pulmonary Exposure to Graphene Oxide and Reduced Graphene Oxide. PLoS One 2017, 12 (6), e0178355 DOI: 10.1371/journal.pone.017835549https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXhslWhsr3M&md5=585e5fa50e54869664f3b270cb1c60cbDifferences in inflammation and acute phase response but similar genotoxicity in mice following pulmonary exposure to graphene oxide and reduced graphene oxideBengtson, Stefan; Knudsen, Kristina B.; Kyjovska, Zdenka O.; Berthing, Trine; Skaug, Vidar; Levin, Marcus; Koponen, Ismo K.; Shivayogimath, Abhay; Booth, Timothy J.; Alonso, Beatriz; Pesquera, Amaia; Zurutuza, Amaia; Thomsen, Birthe L.; Troelsen, Jesper T.; Jacobsen, Nicklas R.; Vogel, UllaPLoS One (2017), 12 (6), e0178355/1-e0178355/25CODEN: POLNCL; ISSN:1932-6203. (Public Library of Science)We investigated toxicity of 2-3 layered >1μm sized graphene oxide (GO) and reduced graphene oxide (rGO) in mice following single intratracheal exposure with respect to pulmonary inflammation, acute phase response (biomarker for risk of cardiovascular disease) and genotoxicity. In addn., we assessed exposure levels of particulate matter emitted during prodn. of graphene in a clean room and in a normal industrial environment using chem. vapor deposition. Toxicity was evaluated at day 1, 3, 28 and 90 days (18, 54 and 162μg/mouse), except for GO exposed mice at day 28 and 90 where only the lowest dose was evaluated. GO induced a strong acute inflammatory response together with a pulmonary (Serum-Amyloid A, Saa3) and hepatic (Saa1) acute phase response. rGO induced less acute, but a const. and prolonged inflammation up to day 90. Lung histopathol. showed particle agglomerates at day 90 without signs of fibrosis. In addn., DNA damage in BAL cells was obsd. across time points and doses for both GO and rGO. In conclusion, pulmonary exposure to GO and rGO induced inflammation, acute phase response and genotoxicity but no fibrosis.
- 50Wang, X.; Duch, M. C.; Mansukhani, N.; Ji, Z.; Liao, Y. P.; Wang, M.; Zhang, H.; Sun, B.; Chang, C. H.; Li, R. Use of a Pro-Fibrogenic Mechanism-Based Predictive Toxicological Approach for Tiered Testing and Decision Analysis of Carbonaceous Nanomaterials. ACS Nano 2015, 9, 3032, DOI: 10.1021/nn507243w50https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXitVers70%253D&md5=78c49c31d11bebfd86429a189471b242Use of a Pro-Fibrogenic Mechanism-Based Predictive Toxicological Approach for Tiered Testing and Decision Analysis of Carbonaceous NanomaterialsWang, Xiang; Duch, Matthew C.; Mansukhani, Nikhita; Ji, Zhaoxia; Liao, Yu-Pei; Wang, Meiying; Zhang, Haiyuan; Sun, Bingbing; Chang, Chong Hyun; Li, Ruibin; Lin, Sijie; Meng, Huan; Xia, Tian; Hersam, Mark C.; Nel, Andre E.ACS Nano (2015), 9 (3), 3032-3043CODEN: ANCAC3; ISSN:1936-0851. (American Chemical Society)Engineered carbonaceous nanomaterials (ECNs), including single-wall carbon nanotubes (SWCNTs), multiwall carbon nanotubes (MWCNTs), graphene, and graphene oxide (GO), are potentially hazardous to the lung. With incremental experience in the use of predictive toxicol. approaches, seeking to relate ECN physicochem. properties to adverse outcome pathways (AOPs), it is logical to explore the existence of a common AOP that allows comparative anal. of broad ECN categories. The authors established an ECN library comprising three different types of SWCNTs, graphene, and graphene oxide (two sizes) for comparative anal. according to a cell-based AOP that also plays a role in the pathogenesis of pulmonary fibrosis. SWCNTs synthesized by Hipco, arc discharge and Co-Mo catalyst (CoMoCAT) methods were obtained in their as-prepd. (AP) state, following which they were further purified (PD) or coated with Pluronic F108 (PF108) or bovine serum albumin (BSA) to improve dispersal and colloidal stability. GO was prepd. as two sizes, GO-small (S) and GO-large (L), while the graphene samples were coated with BSA and PF108 to enable dispersion in aq. soln. In vitro screening showed that AP- and PD-SWCNTs, irresp. of the method of synthesis, as well as graphene (BSA) and GO (S and L) could trigger interleukin-1β (IL-1β) and transforming growth factor-β1 (TGF-β1) prodn. in myeloid (THP-1) and epithelial (BEAS-2B) cell lines, resp. Oropharyngeal aspiration in mice confirmed that AP-Hipco tubes, graphene (BSA-dispersed), GO-S and GO-L could induce IL-1β and TGF-β1 prodn. in the lung in parallel with lung fibrosis. Notably, GO-L was the most pro-fibrogenic material based on rapid kinetics of pulmonary injury. In contrast, PF108-dispersed SWCNTs and -graphene failed to exert fibrogenic effects. Collectively, these data indicate that the dispersal state and surface reactivity of ECNs play key roles in triggering a pro-fibrogenic AOP, which could prove helpful for hazard ranking and a proposed tiered testing approach for large ECN categories.
- 51Vranic, S.; Rodrigues, A. F.; Buggio, M.; Newman, L.; White, M. R. H.; Spiller, D. G.; Bussy, C.; Kostarelos, K. Live Imaging of Label-Free Graphene Oxide Reveals Critical Factors Causing Oxidative-Stress-Mediated Cellular Responses. ACS Nano 2018, 12 (2), 1373– 1389, DOI: 10.1021/acsnano.7b0773451https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1cXhsFOisw%253D%253D&md5=2d227a016212a189d46e9b6055d2d48dLive Imaging of Label-Free Graphene Oxide Reveals Critical Factors Causing Oxidative-Stress-Mediated Cellular ResponsesVranic, Sandra; Rodrigues, Artur Filipe; Buggio, Maurizio; Newman, Leon; White, Michael R. H.; Spiller, David G.; Bussy, Cyrill; Kostarelos, KostasACS Nano (2018), 12 (2), 1373-1389CODEN: ANCAC3; ISSN:1936-0851. (American Chemical Society)The interest in graphene and its translation into com. products have been expanding at high pace. In regard to previously described pulmonary safety concerns for carbon nanomaterials, there is a great need to define parameters guiding interactions between graphene-based materials and pulmonary system. The aim of present study was to det. the importance of two crit. parameters: lateral dimensions of the material and coating with proteins in relation to each other and their pulmonary impact. Endotoxin-free materials with distinct lateral dimensions - s-GO (50 - 200 nm) and l-GO (5 - 15 μm) were produced and thoroughly characterized. Exploiting intrinsic fluorescence of GO and using confocal live-cell imaging, we visualized the behavior of the cells in response to the material in real time. Although BEAS-2B cells internalized GO efficiently, l-GO was linked to higher plasma membrane interactions correlated with elevated ROS levels, pro-inflammatory response and greater cytotoxicity, in agreement with the oxidative stress paradigm. For both GO types, the presence of serum alleviated lipid peroxidn. of plasma membrane and decreased intracellular ROS levels. However, protein coating was not enough to entirely mitigate toxicity and inflammatory response induced by l-GO. In vitro results were validated in vivo, as l-GO was more prone to induce pulmonary granulomatous response in mice compared to s-GO. In conclusion, lateral dimension of GO played more important role than serum protein coating in detg. biol. responses to the material. It was also demonstrated that time-lapse imaging of live cells interacting with label-free GO sheets can be used as a tool to assess GO induced cytotoxicity.
- 52Xu, S.; Zheng, H.; Ma, R.; Wu, D.; Pan, Y.; Yin, C.; Gao, M.; Wang, W.; Li, W.; Liu, S. Vacancies on 2D Transition Metal Dichalcogenides Elicit Ferroptotic Cell Death. Nat. Commun. 2020, 11 (1), 3484, DOI: 10.1038/s41467-020-17300-752https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXhtl2rtr%252FE&md5=7edbe6c932e86048398d64166967c17fVacancies on 2D transition metal dichalcogenides elicit ferroptotic cell deathXu, Shujuan; Zheng, Huizhen; Ma, Ronglin; Wu, Di; Pan, Yanxia; Yin, Chunyang; Gao, Meng; Wang, Weili; Li, Wei; Liu, Sijin; Chai, Zhifang; Li, RuibinNature Communications (2020), 11 (1), 3484CODEN: NCAOBW; ISSN:2041-1723. (Nature Research)Sustainable developments of nanotechnol. necessitate the exploration of structure-activity relationships (SARs) at nano-bio interfaces. While ferroptosis may contribute in the developments of some severe diseases (e.g., Parkinson's disease, stroke and tumors), the cellular pathways and nano-SARs are rarely explored in diseases elicited by nano-sized ferroptosis inducers. Here we find that WS2 and MoS2 nanosheets induce an iron-dependent cell death, ferroptosis in epithelial (BEAS-2B) and macrophage (THP-1) cells, evidenced by the suppression of glutathione peroxidase 4 (GPX4), oxygen radical generation and lipid peroxidn. Notably, nano-SAR anal. of 20 transition metal dichalcogenides (TMDs) disclosures the decisive role of surface vacancy in ferroptosis. We therefore develop methanol and sulfide passivation as safe design approaches for TMD nanosheets. These findings are validated in animal lungs by oropharyngeal aspiration of TMD nanosheets. Overall, our study highlights the key cellular events as well as nano-SARs in TMD-induced ferroptosis, which may facilitate the safe design of nanoproducts.
- 53Moura, J. A.; Meldrum, K.; Doak, S. H.; Clift, M. J. D. Alternative Lung Cell Model Systems for Toxicology Testing Strategies: Current Knowledge and Future Outlook. Seminars in Cell and Developmental Biology. 2023, 147, 70, DOI: 10.1016/j.semcdb.2022.12.00653https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3sXjtFegsA%253D%253D&md5=82408004e001ba6d0f4a4926075bf1c3Alternative lung cell model systems for toxicology testing strategies: Current knowledge and future outlookMoura, Joana A.; Meldrum, Kirsty; Doak, Shareen H.; Clift, Martin J. D.Seminars in Cell & Developmental Biology (2023), 147 (), 70-82CODEN: SCDBFX; ISSN:1084-9521. (Elsevier Ltd.)A review. Due to the current relevance of pulmonary toxicol. (with focus upon air pollution and the inhalation of hazardous materials), it is important to further develop and implement physiol. relevant models of the entire respiratory tract. Lung model development has the aim to create human relevant systems that may replace animal use while balancing cost, laborious nature and regulatory ambition. There is an imperative need to move away from rodent models and implement models that mimic the holistic characteristics important in lung function. The purpose of this review is therefore, to describe and identify the various alternative models that are being applied towards assessing the pulmonary toxicol. of inhaled substances, as well as the current and potential developments of various advanced models and how they may be applied towards toxicol. testing strategies. These models aim to mimic various regions of the lung, as well as implementing different exposure methods with the addn. of various physiol. relevent conditions (such as fluid-flow and dynamic movement). There is further progress in the type of models used with focus on the development of lung-on-a-chip technologies and bioprinting, as well as and the optimization of such models to fill current knowledge gaps within toxicol.
- 54Murphy, F. A.; Poland, C. A.; Duffin, R.; Al-Jamal, K. T.; Nunes, A.; Ali-Boucetta, H.; Byrne, F.; Prina-Mello, A.; Volkov, Y.; Li, S. Length-Dependent Retention of Carbon Nanotubes in the Pleural Space of Mice Initiates Sustained Inflammation and Progressive Fibrosis on the Parietal Pleura. Am. J. Pathol. 2011, 178 (6), 2587– 2600, DOI: 10.1016/j.ajpath.2011.02.04054https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXoslOns74%253D&md5=5011ecbb060e9eab80668d88c468961fLength-dependent retention of carbon nanotubes in the pleural space of mice initiates sustained inflammation and progressive fibrosis on the parietal pleuraMurphy, Fiona A.; Poland, Craig A.; Duffin, Rodger; Al-Jamal, Khuloud T.; Ali-Boucetta, Hanene; Nunes, Antonio; Byrne, Fiona; Prina-Mello, Adriele; Volkov, Yuri; Li, Shouping; Mather, Stephen J.; Bianco, Alberto; Prato, Maurizio; MacNee, William; Wallace, William A.; Kostarelos, Kostas; Donaldson, KenAmerican Journal of Pathology (2011), 178 (6), 2587-2600CODEN: AJPAA4; ISSN:0002-9440. (Elsevier)The fibrous shape of carbon nanotubes (CNTs) raises concern that they may pose an asbestos-like inhalation hazard, leading to the development of diseases, esp. mesothelioma. Direct instillation of long and short CNTs into the pleural cavity, the site of mesothelioma development, produced asbestos-like length-dependent responses. The response to long CNTs and long asbestos was characterized by acute inflammation, leading to progressive fibrosis on the parietal pleura, where stomata of strictly defined size limit the egress of long, but not short, fibers. This was confirmed by demonstrating clearance of short, but not long, CNT and nickel nanowires and by visualizing the migration of short CNTs from the pleural space by single-photon emission computed tomog. imaging. Our data confirm the hypothesis that, although a proportion of all deposited particles passes through the pleura, the pathogenicity of long CNTs and other fibers arises as a result of length-dependent retention at the stomata on the parietal pleura.
- 55Schinwald, A.; Donaldson, K. Use of Back-Scatter Electron Signals to Visualise Cell/Nanowires Interactions in Vitro and in Vivo; Frustrated Phagocytosis of Long Fibres in Macrophages and Compartmentalisation in Mesothelial Cells in Vivo. Part. Fibre Toxicol. 2012, 9, 34, DOI: 10.1186/1743-8977-9-3455https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC38XhvVSiu73O&md5=4d21ebe21a7108af2de8e422014340c4Use of back-scatter electron signals to visualise cell/nanowires interactions in vitro and in vivo; frustrated phagocytosis of long fibres in macrophages and compartmentalisation in mesothelial cells in vivoSchinwald, Anja; Donaldson, KenParticle and Fibre Toxicology (2012), 9 (), 34CODEN: PFTABQ; ISSN:1743-8977. (BioMed Central Ltd.)Background: Frustrated phagocytosis has been stated as an important factor in the initiation of an inflammatory response after fiber exposure. The length of fibrous structures has been linked to the potential of fibers to induce adverse health effects for at least 40 years. However, we only recently reported for the first time the threshold length for fiber-induced inflammation in the pleural space and we implicated frustrated phagocytosis in the pro-inflammatory effects of long fibers. This study extends the examn. of the threshold value for frustrated phagocytosis using well-defined length classes of silver nanowires (AgNW) ranging from 3-28 μm and describes in detail the morphol. of frustrated phagocytosis using a novel technique and also describes compartmentalization of fibers in the pleural space. Methods: A novel technique, backscatter SEM (BSE) was used to study frustrated phagocytosis since it provides high-contrast detection of nanowires, allowing clear discrimination between the nanofibers and other cellular features. A human monocyte-derived macrophage cell line THP-1 was used to investigate cell-nanowire interaction in vitro and the parietal pleura, the site of fiber retention after inhalation exposure was chosen to visualize the cell-fiber interaction in vivo after direct pleural installation of AgNWs. Results: The length cut-off value for frustrated phagocytosis differs in vitro and in vivo. While in vitro frustrated phagocytosis could be obsd. with fibers ≥14 μm, in vivo studies showed incomplete uptake at a fiber length of ≥10 μm. Recently we showed that inflammation in the pleural space after intrapleural injection of the same nanofiber panel occurs at a length of ≥5 μm. This onset of inflammation does not correlate with the onset of frustrated phagocytosis as shown in this study, leading to the conclusion that intermediate length fibers fully enclosed within macrophages as well as frustrated phagocytosis are assocd. with a pro-inflammatory state in the pleural space. We further showed that fibers compartmentalize in the mesothelial cells at the parietal pleura as well as in inflammatory cells in the pleural space. Conclusion: BSE is a useful way to clearly distinguish between fibers that are, or are not, membrane-bounded. Using this method we were able to show differences in the threshold length at which frustrated phagocytosis occurred between in vitro and in vivo models. Visualising nanowires in the pleura demonstrated at least 2 compartments - in leukocyte aggregations and in the mesothelium - which may have consequences for long term pathol. in the pleural space including mesothelioma.
- 56Liu, Y.; Zhao, Y.; Sun, B.; Chen, C. Understanding the Toxicity of Carbon Nanotubes. Acc. Chem. Res. 2013, 46 (3), 702– 713, DOI: 10.1021/ar300028m56https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC38Xhtl2iurbO&md5=9d1c85c6d394bff5f9d2c4ec1da97f25Understanding the toxicity of carbon nanotubesLiu, Ying; Zhao, Yuliang; Sun, Baoyun; Chen, ChunyingAccounts of Chemical Research (2013), 46 (3), 702-713CODEN: ACHRE4; ISSN:0001-4842. (American Chemical Society)A review. Because of their unique phys., chem., elec., and mech. properties, carbon nanotubes (CNTs) have attracted a great deal of research interest and have many potential applications. As large-scale prodn. and application of CNTs increases, the general population is more likely to be exposed to CNTs either directly or indirectly, which has prompted considerable attention about human health and safety issues related to CNTs. Although considerable exptl. data related to CNT toxicity at the mol., cellular, and whole animal levels have been published, the results are often conflicting. Therefore, a systematic understanding of CNT toxicity is needed but has not yet been developed. In this Account, we highlight recent investigations into the basis of CNT toxicity carried out by our team and by other labs. We focus on several important factors that explain the disparities in the exptl. results of nanotoxicity, such as impurities, amorphous carbon, surface charge, shape, length, agglomeration, and layer nos. The exposure routes, including inhalation, i.v. injection, or dermal or oral exposure, can also influence the in vivo behavior and fate of CNTs. The underlying mechanisms of CNT toxicity include oxidative stress, inflammatory responses, malignant transformation, DNA damage and mutation (errors in chromosome no. as well as disruption of the mitotic spindle), the formation of granulomas, and interstitial fibrosis. These findings provide useful insights for de novo design and safe application of carbon nanotubes and their risk assessment to human health. To obtain reproducible and accurate results, researchers must establish stds. and reliable detection methods, use std. CNT samples as a ref. control, and study the impact of various factors systematically. In addn., researchers need to examine multiple types of CNTs, different cell lines and animal species, multidimensional evaluation methods, and exposure conditions. To make results comparable among different institutions and countries, researchers need to standardize choices in toxicity testing such as that of cell line, animal species, and exposure conditions. The knowledge presented here should lead to a better understanding of the key factors that can influence CNT toxicity so that their unwanted toxicity might be avoided.
- 57Murphy, F. A.; Poland, C. A.; Duffin, R.; Al-Jamal, K. T.; Nunes, A.; Ali-Boucetta, H.; Byrne, F.; Prina-Mello, A.; Volkov, Y.; Li, S. Length-Dependent Retention of Carbon Nanotubes in the Pleural Space of Mice Initiates Sustained Inflammation and Progressive Fibrosis on the Parietal Pleura. Am. J. Pathol. 2011, 178, 2587– 2600, DOI: 10.1016/j.ajpath.2011.02.04057https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXoslOns74%253D&md5=5011ecbb060e9eab80668d88c468961fLength-dependent retention of carbon nanotubes in the pleural space of mice initiates sustained inflammation and progressive fibrosis on the parietal pleuraMurphy, Fiona A.; Poland, Craig A.; Duffin, Rodger; Al-Jamal, Khuloud T.; Ali-Boucetta, Hanene; Nunes, Antonio; Byrne, Fiona; Prina-Mello, Adriele; Volkov, Yuri; Li, Shouping; Mather, Stephen J.; Bianco, Alberto; Prato, Maurizio; MacNee, William; Wallace, William A.; Kostarelos, Kostas; Donaldson, KenAmerican Journal of Pathology (2011), 178 (6), 2587-2600CODEN: AJPAA4; ISSN:0002-9440. (Elsevier)The fibrous shape of carbon nanotubes (CNTs) raises concern that they may pose an asbestos-like inhalation hazard, leading to the development of diseases, esp. mesothelioma. Direct instillation of long and short CNTs into the pleural cavity, the site of mesothelioma development, produced asbestos-like length-dependent responses. The response to long CNTs and long asbestos was characterized by acute inflammation, leading to progressive fibrosis on the parietal pleura, where stomata of strictly defined size limit the egress of long, but not short, fibers. This was confirmed by demonstrating clearance of short, but not long, CNT and nickel nanowires and by visualizing the migration of short CNTs from the pleural space by single-photon emission computed tomog. imaging. Our data confirm the hypothesis that, although a proportion of all deposited particles passes through the pleura, the pathogenicity of long CNTs and other fibers arises as a result of length-dependent retention at the stomata on the parietal pleura.
- 58Osmond-McLeod, M. J.; Poland, C. A.; Murphy, F.; Waddington, L.; Morris, H.; Hawkins, S. C.; Clark, S.; Aitken, R.; McCall, M. J.; Donaldson, K. Durability and Inflammogenic Impact of Carbon Nanotubes Compared with Asbestos Fibres. Part. Fibre Toxicol. 2011, 8, 15, DOI: 10.1186/1743-8977-8-1558https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXmt1Omur4%253D&md5=a8ae6fd962c052f8b7511bc65c88bce3Durability and inflammogenic impact of carbon nanotubes compared with asbestos fibresOsmond-McLeod, Megan J.; Poland, Craig A.; Murphy, Fiona; Waddington, Lynne; Morris, Howard; Hawkins, Stephen C.; Clark, Steve; Aitken, Rob; McCall, Maxine J.; Donaldson, KenParticle and Fibre Toxicology (2011), 8 (), 15CODEN: PFTABQ; ISSN:1743-8977. (BioMed Central Ltd.)Background: It has been suggested that carbon nanotubes might conform to the fiber pathogenicity paradigm that explains the toxicities of asbestos and other fibers on a continuum based on length, aspect ratio and biopersistence. Some types of carbon nanotubes satisfy the first two aspects of the fiber paradigm but only recently has their biopersistence begun to be investigated. Biopersistence is complex and requires in vivo testing and anal. However durability, the chem. mimicking of the process of fiber dissoln. using in vitro treatment, is closely related to biopersistence and more readily detd. Here, we describe an exptl. process to det. the durability of four types of carbon nanotubes in simulated biol. fluid (Gambles soln.), and their subsequent pathogenicity in vivo using a mouse model sensitive to inflammogenic effects of fibers. The in vitro and in vivo results were compared with well-characterized glass wool and asbestos fiber controls. Results: After incubation for up to 24 wk in Gambles soln., our control fibers were recovered at percentages consistent with their known in vitro durabilities and/or in vivo persistence, and three out of the four types of carbon nanotubes tested [single walled (CNTSW) and multi walled (CNTTANG2, CNTSPIN)] showed no, or minimal, loss of mass or change in fiber length or morphol. when examd. by electron microscopy. However, the fourth type [multi walled (CNTLONG1)] lost 30% of its original mass within the first three weeks of incubation, after which there was no further loss. Electron microscopy of CNTLONG1 samples incubated for 10 wk confirmed that the proportion of long fibers had decreased compared to samples briefly exposed to the Gambles soln. This loss of mass and fiber shortening was accompanied by a loss of pathogenicity when injected into the peritoneal cavities of C57Bl/6 mice compared to fibers incubated briefly. CNTSW did not elicit an inflammogenic effect in the peritoneal cavity assay used here. Conclusions: These results support the view that carbon nanotubes are generally durable but may be subject to bio-modification in a sample-specific manner. They also suggest that pristine carbon nanotubes, either individually or in rope-like aggregates of sufficient length and aspect ratio, can induce asbestos-like responses in mice, but that the effect may be mitigated for certain types that are less durable in biol. systems. Results indicate that durable carbon nanotubes that are either short or form tightly bundled aggregates with no isolated long fibers are less inflammogenic in fiber specific assays.
- 59Gieseck, R. L.; Wilson, M. S.; Wynn, T. A. Type 2 Immunity in Tissue Repair and Fibrosis. Nature Reviews Immunology. 2018, 18, 62– 76, DOI: 10.1038/nri.2017.9059https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXhtl2ru7fI&md5=9b306b272e5e70589d4fb0c2432ef5d8Type 2 immunity in tissue repair and fibrosisGieseck, Richard L., III; Wilson, Mark S.; Wynn, Thomas A.Nature Reviews Immunology (2018), 18 (1), 62-76CODEN: NRIABX; ISSN:1474-1733. (Nature Research)Type 2 immunity is characterized by the prodn. of IL-4, IL-5, IL-9 and IL-13, and this immune response is commonly obsd. in tissues during allergic inflammation or infection with helminth parasites. However, many of the key cell types assocd. with type 2 immune responses - including T helper 2 cells, eosinophils, mast cells, basophils, type 2 innate lymphoid cells and IL-4- and IL-13-activated macrophages - also regulate tissue repair following injury. Indeed, these cell populations engage in crucial protective activity by reducing tissue inflammation and activating important tissue-regenerative mechanisms. Nevertheless, when type 2 cytokine-mediated repair processes become chronic, over-exuberant or dysregulated, they can also contribute to the development of pathol. fibrosis in many different organ systems. In this Review, we discuss the mechanisms by which type 2 immunity contributes to tissue regeneration and fibrosis following injury.
- 60Wynn, T. A. Fibrotic Disease and the TH1/TH2 Paradigm. Nature Reviews Immunology. 2004, 4, 583– 594, DOI: 10.1038/nri141260https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD2cXmtFWktr0%253D&md5=eb3bd245546d25a3e06df136bfe2602aFibrotic disease and the TH1/TH2 paradigmWynn, Thomas A.Nature Reviews Immunology (2004), 4 (8), 583-594CODEN: NRIABX; ISSN:1474-1733. (Nature Publishing Group)A review. Tissue fibrosis (scarring) is a leading cause of morbidity and mortality. Current treatments for fibrotic disorders, such as idiopathic pulmonary fibrosis, hepatic fibrosis and systemic sclerosis, target the inflammatory cascade, but they have been widely unsuccessful, largely because the mechanisms that are involved in fibrogenesis are now known to be distinct from those involved in inflammation. Several exptl. models have recently been developed to dissect the mol. mechanisms of wound healing and fibrosis. It is hoped that by better understanding the immunol. mechanisms that initiate, sustain and suppress the fibrotic process, the authors will achieve the elusive goal of targeted and effective therapeutics for fibroproliferative diseases.
- 61Wynn, T. A.; Vannella, K. M. Macrophages in Tissue Repair, Regeneration, and Fibrosis. Immunity. 2016, 44, 450– 462, DOI: 10.1016/j.immuni.2016.02.01561https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28Xktlahs70%253D&md5=bb0e131d752c2c6fd017fb25aad5ee08Macrophages in Tissue Repair, Regeneration, and FibrosisWynn, Thomas A.; Vannella, Kevin M.Immunity (2016), 44 (3), 450-462CODEN: IUNIEH; ISSN:1074-7613. (Elsevier Inc.)Inflammatory monocytes and tissue-resident macrophages are key regulators of tissue repair, regeneration, and fibrosis. After tissue injury, monocytes and macrophages undergo marked phenotypic and functional changes to play crit. roles during the initiation, maintenance, and resoln. phases of tissue repair. Disturbances in macrophage function can lead to aberrant repair, such that uncontrolled prodn. of inflammatory mediators and growth factors, deficient generation of anti-inflammatory macrophages, or failed communication between macrophages and epithelial cells, endothelial cells, fibroblasts, and stem or tissue progenitor cells all contribute to a state of persistent injury, and this could lead to the development of pathol. fibrosis. In this review, we discuss the mechanisms that instruct macrophages to adopt pro-inflammatory, pro-wound-healing, pro-fibrotic, anti-inflammatory, anti-fibrotic, pro-resolving, and tissue-regenerating phenotypes after injury, and we highlight how some of these mechanisms and macrophage activation states could be exploited therapeutically.
- 62Fadeel, B.; Kostarelos, K. Grouping All Carbon Nanotubes into a Single Substance Category Is Scientifically Unjustified. Nature Nanotechnology. 2020, 15, 164, DOI: 10.1038/s41565-020-0654-062https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXktFelsr4%253D&md5=26bf8c8a8a419d8be2ca5129f66d4bd4Grouping all carbon nanotubes into a single substance category is scientifically unjustifiedFadeel, Bengt; Kostarelos, KostasNature Nanotechnology (2020), 15 (3), 164CODEN: NNAABX; ISSN:1748-3387. (Nature Research)There is no expanded citation for this reference.
- 63Del Rio Castillo, A. E.; Pellegrini, V.; Ansaldo, A.; Ricciardella, F.; Sun, H.; Marasco, L.; Buha, J.; Dang, Z.; Gagliani, L.; Lago, E. High-Yield Production of 2D Crystals by Wet-Jet Milling. Mater. Horizons 2018, 5 (5), 890– 904, DOI: 10.1039/C8MH00487K63https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1cXht1OjtLzM&md5=279c9077c7e2002ff0f973c2f80ab5feHigh-yield production of 2D crystals by wet-jet millingDel Rio Castillo, A. E.; Pellegrini, V.; Ansaldo, A.; Ricciardella, F.; Sun, H.; Marasco, L.; Buha, J.; Dang, Z.; Gagliani, L.; Lago, E.; Curreli, N.; Gentiluomo, S.; Palazon, F.; Prato, M.; Oropesa-Nunez, R.; Toth, P. S.; Mantero, E.; Crugliano, M.; Gamucci, A.; Tomadin, A.; Polini, M.; Bonaccorso, F.Materials Horizons (2018), 5 (5), 890-904CODEN: MHAOBM; ISSN:2051-6355. (Royal Society of Chemistry)Efficient and scalable prodn. of two-dimensional (2D) materials is required to overcome technol. hurdles towards the creation of a 2D-material-based industry. Here, we present a novel approach developed for the exfoliation of layered crystals, i.e., graphite, hexagonal-boron nitride and transition metal dichalcogenides. The process is based on high-pressure wet-jet-milling (WJM), resulting in a 2 L h-1 prodn. of 10 g L-1 of single- and few-layer 2D crystal flakes in dispersion making the scaling-up more affordable. The WJM process enables the prodn. of defect-free and high quality 2D-crystal dispersions on a large scale, opening the way for their full exploitation in different com. applications, e.g., as anode active material in lithium ion batteries, as reinforcement in polymer-graphene composites, and as conductive inks, as we demonstrate in this report.
- 64Del Rio Castillo, A. E.; Ansaldo, A.; Pellegrini, V.; Bonaccorso, F. US Patent Exfoliation of Layered Materials by Wet-Jet Milling Techniques. US10407308B2, 2019.There is no corresponding record for this reference.
- 65Smith, M. W.; Jordan, K. C.; Park, C.; Kim, J. W.; Lillehei, P. T.; Crooks, R.; Harrison, J. S. Very Long Single-and Few-Walled Boron Nitride Nanotubes via the Pressurized Vapor/Condenser Method. Nanotechnology 2009, 20 (50), 505604, DOI: 10.1088/0957-4484/20/50/50560465https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1MXhs1SrtL7P&md5=e66ba9b2a408739155497c2670ece6faVery long single- and few-walled boron nitride nanotubes via the pressurized vapor/condenser methodSmith, Michael W.; Jordan, Kevin C.; Park, Cheol; Kim, Jae-Woo; Lillehei, Peter T.; Crooks, Roy; Harrison, Joycelyn S.Nanotechnology (2009), 20 (50), 505604/1-505604/6CODEN: NNOTER; ISSN:1361-6528. (Institute of Physics Publishing)A new method for producing long, small-diam., single- and few-walled, boron nitride nanotubes (BNNTs) in macroscopic quantities is reported. The pressurized vapor/condenser (PVC) method produces, without catalysts, highly cryst., very long, small-diam., BNNTs. Palm-sized, cotton-like masses of BNNT raw material were grown by this technique and spun directly into centimeters-long yarn. Nanotube lengths were obsd. to be 100 times that of those grown by the most closely related method. Self-assembly and growth models for these long BNNTs are discussed.
- 66Gutruf, P.; Yin, R. T.; Lee, K. B.; Ausra, J.; Brennan, J. A.; Qiao, Y.; Xie, Z.; Peralta, R.; Talarico, O.; Murillo, A. Wireless, Battery-Free, Fully Implantable Multimodal and Multisite Pacemakers for Applications in Small Animal Models. Nat. Commun. 2019, 10 (1), 5742, DOI: 10.1038/s41467-019-13637-w66https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1MXisVGjsb%252FE&md5=4d1b76d9078c7e23171fea0ff4766b9fWireless, battery-free, fully implantable multimodal and multisite pacemakers for applications in small animal modelsGutruf, Philipp; Yin, Rose T.; Lee, K. Benjamin; Ausra, Jokubas; Brennan, Jaclyn A.; Qiao, Yun; Xie, Zhaoqian; Peralta, Roberto; Talarico, Olivia; Murillo, Alejandro; Chen, Sheena W.; Leshock, John P.; Haney, Chad R.; Waters, Emily A.; Zhang, Changxing; Luan, Haiwen; Huang, Yonggang; Trachiotis, Gregory; Efimov, Igor R.; Rogers, John A.Nature Communications (2019), 10 (1), 5742CODEN: NCAOBW; ISSN:2041-1723. (Nature Research)Small animals support a wide range of pathol. phenotypes and genotypes as versatile, affordable models for pathogenesis of cardiovascular diseases and for exploration of strategies in electrotherapy, gene therapy, and optogenetics. Pacing tools in such contexts are currently limited to tethered embodiments that constrain animal behaviors and exptl. designs. Here, we introduce a highly miniaturized wireless energy-harvesting and digital communication electronics for thin, miniaturized pacing platforms weighing 110 mg with capabilities for subdermal implantation and tolerance to over 200,000 multiaxial cycles of strain without degrdn. in elec. or optical performance. Multimodal and multisite pacing in ex vivo and in vivo studies over many days demonstrate chronic stability and excellent biocompatibility. Optogenetic stimulation of cardiac cycles with in-animal control and induction of heart failure through chronic pacing serve as examples of modes of operation relevant to fundamental and applied cardiovascular research and biomedical technol.
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Supporting Information
The Supporting Information is available free of charge at https://pubs.acs.org/doi/10.1021/acsnano.3c06599.
Numerical results of XPS survey; RT-qPCR primers; physicochemical characteristics of BN materials; Raman, TGA, XPS analysis of the materials; representative pictures of BAL cells cytospun and differentially stained; AA protein measurement in blood samples (PDF)
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