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Issue 25, 2020
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High-throughput single-cell analysis of exosome mediated dual drug delivery, in vivo fate and synergistic tumor therapy

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Abstract

Exosomes could serve as delivery platforms, owing to their good biocompatibility, stability, and long blood circulation time. Tracking the biological fate of exosomes in vivo is essential for evaluating their functions, delivery efficacy, and biosafety, and it is invaluable for guiding exosome-based therapy. Here, we merged a single-cell technique, mass cytometry, with in vivo uptake analysis to comprehensively reveal the fate of exosomes at the single-cell level. In tandem with multivariate cellular phenotyping, in vivo uptake of exosomes labeled with heavy metal-containing tags was quantified in a high-throughput manner. Interestingly, an organ-dependent uptake landscape of exosomes by diverse cell types was distinctly demonstrated, which implied that cancer cells seemed to preferably take up more released drugs from the exosomes. Using these cellular insights, the administration method of drug-loaded exosomes was optimized to elevate their accumulation in tumor sites and minimize their spread into healthy organs. Dual drug-loaded exosomes were locally administered and superior synergistic tumor treatment effects were achieved in a solid tumor model. The disclosure of exosome cellular distribution, together with the successful engineering of exosomes with multiple anticancer capacities, provides a new level of insight into optimizing and enhancing exosome-based drug delivery and synergistic tumor therapy.

Graphical abstract: High-throughput single-cell analysis of exosome mediated dual drug delivery, in vivo fate and synergistic tumor therapy

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Supplementary files

Article information


Submitted
23 Mar 2020
Accepted
04 Jun 2020
First published
05 Jun 2020

Nanoscale, 2020,12, 13742-13756
Article type
Paper

High-throughput single-cell analysis of exosome mediated dual drug delivery, in vivo fate and synergistic tumor therapy

J. Wang, G. Li, C. Tu, X. Chen, B. Yang, Y. Huo, Y. Li, A. Chen, P. Lan, Y. S. Zhang and M. Xie, Nanoscale, 2020, 12, 13742
DOI: 10.1039/D0NR02344B

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