Poly(lactic-co-glycolic acid)/Polyethylenimine Nanocarriers for Direct Genetic Reprogramming of MicroRNA Targeting Cardiac Fibroblasts

Abstract

Cardiovascular disease remains a major cause of deaths globally. Post-heart-infarction, the most abundant cell type of heart, ‘fibroblasts’ undergoes a series of culminating events that lead to fibrotic scar tissue. In many organisms, injury to the heart can be restored but the adult human heart is unable to efficiently regenerate after ischemic injury. So, the inefficiency of heart to regenerate on its own after ischemic injury accounts for its reprogramming. Herein, we demonstrate the effect of microRNAs encapsulating Poly (lactic-co-glycolic acid) (PLGA)-Polyethylenimine (PEI) nanocarriers for direct reprogramming of cardiac fibroblast to cardiomyocyte-like cells. Dual, cardiac muscle specific miRNA (miR-1 and miR-133a) polyplexes were encapsulated in biodegradable PLGA nanospheres. Cytocompatibility of the nanocomplexes were evaluated by various in vitro assays, confirming their safety profile. The change in cardiac fibroblast phenotype to cardiomyocyte was identified by the expression of late-stage s...