Our research team is developing therapeutic techniques based on exosomes (extracellular vesicles, EVs) and peptide chemistry to deliver therapeutic/diagnostic molecules into targeted cells. Because of pharmaceutical advantages of the EVs as carriers for intracellular delivery of therapeutic molecules, we are trying to develop techniques to easily modify biofunctional peptides on EVs membranes for receptor target and enhanced cellular uptake of the EVs. In this presentation, modification techniques using biofunctional peptides such as arginine-rich cell-penetrating peptides (CPPs, macropinocytosis induction), artificial coiled-coil peptides (receptor target), membrane fusion peptides (cytosolic release) will be introduced. And newly developed EVs decorated with cell-penetrating sC18 peptides, which are derived from cationic antimicrobial protein, CAP18, will be also presented and discussed for cancer targeting.<br/>Macropinocytosis has been shown to be very important for cellular EV uptake. Therefore, our research group developed the methods for modification of arginine-rich CPPs on EV membranes using chemical linkers or acylation technique, which can induce clustering of proteoglycans (e.g. syndecan-4) and macropinocytosis signal transduction. In the research of artificial coiled-coil peptides, the artificial leucine zipper peptide-modified EVs recognize the peptide-tagged receptor expression on targeted cells. Stearylation of branched sC18 peptides were easily modified on the EVs by their insertion of hydrophobic moiety in EV membranes, resulted in effective induction of macropinocytosis and cancer cellular uptake. These experimental techniques will contribute to development for the EV-based intracellular delivery systems.

Intracellular delivery techniques using biofunctional peptide-modified exosomes

ACS Spring 2022

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.