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DOI10.1073/pnas.2020241118
Engineering exosome polymer hybrids by atom transfer radical polymerization
Lathwal S.; Yerneni S.S.; Boye S.; Muza U.L.; Takahashi S.; Sugimoto N.; Lederer A.; Das S.R.; Campbell P.G.; Matyjaszewski K.
发表日期2021
ISSN00278424
卷号118期号:2
英文摘要Exosomes are emerging as ideal drug delivery vehicles due to their biological origin and ability to transfer cargo between cells. However, rapid clearance of exogenous exosomes from the circulation as well as aggregation of exosomes and shedding of surface proteins during storage limit their clinical translation. Here, we demonstrate highly controlled and reversible functionalization of exosome surfaces with well-defined polymers that modulate the exosome's physiochemical and pharmacokinetic properties. Using cholesterol-modified DNA tethers and complementary DNA block copolymers, exosome surfaces were engineered with different biocompatible polymers. Additionally, polymers were directly grafted from the exosome surface using biocompatible photo-mediated atom transfer radical polymerization (ATRP). These exosome polymer hybrids (EPHs) exhibited enhanced stability under various storage conditions and in the presence of proteolytic enzymes. Tuning of the polymer length and surface loading allowed precise control over exosome surface interactions, cellular uptake, and preserved bioactivity. EPHs show fourfold higher blood circulation time without altering tissue distribution profiles. Our results highlight the potential of precise nanoengineering of exosomes toward developing advanced drug and therapeutic delivery systems using modern ATRP methods. © 2021 National Academy of Sciences. All rights reserved.
英文关键词ATRP; Exosome; Polymer; Polymer biohybrid
语种英语
来源期刊Proceedings of the National Academy of Sciences of the United States of America
文献类型期刊论文
条目标识符http://gcip.llas.ac.cn/handle/2XKMVOVA/181055
作者单位Department of Chemistry, Carnegie Mellon University, Pittsburgh, PA 15213, United States; Center for Nucleic Acids Science and Technology, Carnegie Mellon University, Pittsburgh, PA 15213, United States; Department of Biomedical Engineering, Carnegie Mellon University, Pittsburgh, PA 15213, United States; Polymer Separation Group, Leibniz-Institut für Polymerforschung Dresden e.V., Dresden, 01069, Germany; Department of Chemistry and Polymer Science, Stellenbosch University, Matieland, Stellenbosch, 7602, South Africa; Frontier Institute for Biomolecular Engineering Research, Konan University, Kobe, 650-0047, Japan; Graduate School of Frontiers of Innovative Research in Science and Technology, Konan University, Kobe, 650-0047, Japan; Faculty of Chemistry and Food Chemistry, Technische Universität Dresden, Dresden, 01062, Germany; Engineering Research Accelerator, Carnegie Mellon University, Pittsburgh, PA 15213, United States
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Lathwal S.,Yerneni S.S.,Boye S.,et al. Engineering exosome polymer hybrids by atom transfer radical polymerization[J],2021,118(2).
APA Lathwal S..,Yerneni S.S..,Boye S..,Muza U.L..,Takahashi S..,...&Matyjaszewski K..(2021).Engineering exosome polymer hybrids by atom transfer radical polymerization.Proceedings of the National Academy of Sciences of the United States of America,118(2).
MLA Lathwal S.,et al."Engineering exosome polymer hybrids by atom transfer radical polymerization".Proceedings of the National Academy of Sciences of the United States of America 118.2(2021).
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