Self-assembly of stem cell membrane-camouflaged nanocomplex for microRNA-mediated repair of myocardial infarction injury

Abstract

Mesenchymal stem cells-derived exosomes have shown promising therapeutic effect on myocardial infarction (MI). The major hurdles remain for the use of exosomes primarily due to the low yields from cell cultures coupled with complicated purification processes. Herein we report the self-assembly of stem cell membrane-camouflaged exosome-mimicking nanocomplex that recapitulates exosome functions, achieving efficient microRNA (miRNA) delivery and miRNA-mediated myocardial repair. The nanocomplex is constructed via the self-assembly of mesenchymal stem cell membrane on miRNA loaded mesoporous silica nanoparticle surface, which enables high miRNA loading capacity and protects miRNA from degradation in body fluid. The nanocomplex can escape the clearance of immunologic system, and target to ischemic injured cardiomyocytes. miRNA is triggered to release and binds to target mRNA, which inhibits the translation of apoptosis-related proteins, and consequently promotes the proliferation of cardiomyocytes. In the MI mouse model, the administration of exosome-mimicking nanocomplex effectively leads to preservation of viable myocardium and augmentation of cardiac functions.