Engineering exosome polymer hybrids by atom transfer radical polymerization

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

  • Sushil Lathwal - , Carnegie Mellon University (Author)
  • Saigopalakrishna S. Yerneni - , Carnegie Mellon University (Author)
  • Susanne Boye - , Leibniz Institute of Polymer Research Dresden (Author)
  • Upenyu L. Muza - , University of Stellenbosch (Author)
  • Shuntaro Takahashi - , Konan University (Author)
  • Naoki Sugimoto - , Konan University (Author)
  • Albena Lederer - , Leibniz Institute of Polymer Research Dresden, University of Stellenbosch, TUD Dresden University of Technology (Author)
  • Subha R. Das - , Carnegie Mellon University (Author)
  • Phil G. Campbell - , Carnegie Mellon University (Author)
  • Krzysztof Matyjaszewski - , Carnegie Mellon University (Author)

Abstract

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.

Details

Original languageEnglish
Article numbere2020241118
JournalProceedings of the National Academy of Sciences of the United States of America
Volume118
Issue number2
Publication statusPublished - 12 Jan 2021
Peer-reviewedYes

External IDs

PubMed 33384328

Keywords

ASJC Scopus subject areas

Keywords

  • ATRP, Exosome, Polymer, Polymer biohybrid