Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 118, Issue 2, Pages -Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.2020241118
Keywords
polymer; ATRP; exosome; polymer biohybrid
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Funding
- Erasmus+ grant
- Ministry of Education, Culture, Sports, Science and Technology, Japan Society for the Promotion of Science [JP17H06351]
- CMU-Biohybrid Organ Center Seed Funding
- NSF [DMR 1501324]
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The controlled and reversible functionalization of exosome surfaces with well-defined polymers can modulate the physiological and pharmacokinetic properties of exosomes, enhancing their potential clinical applications. By using modern ATRP methods, exosome polymer hybrids (EPHs) exhibit improved stability and blood circulation time, without altering tissue distribution profiles, making them promising drug delivery systems for advanced therapeutics.
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.
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