On-Site Stimulation of Dendritic Cells by Cancer-Derived Extracellular Vesicles on a Core-Shell Nanowire Platform

核壳纳米线平台上癌症衍生的细胞外囊泡对树突状细胞进行现场刺激

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作者:Min Zhang, Miki Ono, Shota Kawaguchi, Mikiko Iida, Kunanon Chattrairat, Zetao Zhu, Kazuki Nagashima, Takeshi Yanagida, Junya Yamaguchi, Hiroyoshi Nishikawa, Atsushi Natsume, Yoshinobu Baba, Takao Yasui

Abstract

Extracellular vesicles (EVs) contain a subset of proteins, lipids, and nucleic acids that maintain the characteristics of the parent cell. Immunotherapy using EVs has become a focus of research due to their unique features and bioinspired applications in cancer treatment. Unlike conventional immunotherapy using tumor fragments, EVs can be easily obtained from bodily fluids without invasive actions. We previously fabricated nanowire devices that were specialized for EV collection, but they were not suitable for cell culturing. In this study, we fabricated a ZnO/Al2O3 core-shell nanowire platform that could collect more than 60% of the EVs from the cell supernatant. Additionally, we could continue to culture dendritic cells (DCs) on the platform as an artificial lymph node to investigate cell maturation into antigen-presenting cells. Finally, using this platform, we reproduced a series of on-site immune processes that are among the pivotal immune functions of DCs and include such processes as antigen uptake, antigen presentation, and endocytosis of cancer-derived EVs. This platform provides a new ex vivo tool for EV-DC-mediated immunotherapies.

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