Engineering extracellular vesicles with platelet membranes fusion enhanced targeted therapeutic angiogenesis in a mouse model of myocardial ischemia reperfusion

Abstract

Therapeutic angiogenesis is one promising strategy for the treatment of ischemic heart disease, which is the leading cause of death globally. In recent years, extracellular vesicles (EVs) have quickly gained much attention as a cell-free approach to stimulate angiogenesis. However, clinical applications of EVs are limited by their insufficient targeting capability. Herein, we introduce a method to enhance therapeutic angiogenesis based on platelet membrane-engineered EVs. METHODS: Platelet-mimetic EVs (P-EVs) were fabricated by fusing the membranes of EVs with platelet membranes by extrusion. A mouse model of myocardial ischemia reperfusion (MI/R) was established and injected with PBS, EVs, and P-EVs to evaluate their targeting ability and therapeutic angiogenesis efficacy. RESULTS: P-EVs inherited the adhesive proteins and natural targeting ability to injured vasculature of platelets and retained the pro-angiogenic potential of EVs. In the MI/R model, P-EVs preferentially accumulated in the injured endothelium of the ischemic hearts and enhanced the angiogenesis potency of EVs. CONCLUSIONS: This engineering strategy to modify pre-isolated EVs with platelet membranes by membrane fusion bestows EVs with the targeting ability of platelets and offers an exciting opportunity to design other targeted EVs fused with cell membranes from different sources for therapeutic angiogenesis.