Engineering Dual Peptide-Decorated Extracellular Vesicles to Enhance Retention and Functional Recovery After Myocardial Infarction

Abstract

Myocardial infarction causes irreversible loss of cardiomyocytes, while inflammation and fibrosis further compromise cardiac function. Extracellular vesicles (EVs) can deliver reparative signals, but their therapeutic potential is limited by rapid clearance from injured cardiac tissue. This project advances an engineered EV platform that combines zippersomes including ZIP1 and ZIP2, complementary “zipper” proteins designed to enhance cardiac retention, with SDKP, a therapeutic component aimed at limiting fibrosis. During SURF, I produced SDKP, ZIP1, and ZIP2 from bacterial cultures; isolated, purified, and evaluated the proteins using ÄKTA chromatography and protein assays; and dialyzed, lyophilized, and stored them for downstream EV engineering and preclinical testing. By establishing the complete SDKP + ZIP1 + ZIP2 protein toolkit, this work provides the foundation for testing whether enhanced EV retention can be paired with a defined therapeutic component to further support cardiac repair after myocardial infarction.