Targeted miR-21 loaded liposomes for acute myocardial infarction†
Abstract
Acute and persistent myocardial ischemia is the main cause of acute myocardial infarction (AMI) and heart failure. MicroRNA-21(miR-21) contributes to the pathophysiological consequences of acute myocardial infarction by targeting downstream crucial regulators. Thus, miR-21 mimics are a promising strategy for the treatment of AMI. However, their poor stability and insufficient cellular uptake are the major challenges. Herein, we encapsulated miR-21 mimics into liposomes modified with the cardiac troponin T (cTnT) antibody for targeted delivery of miR-21(cT-21-LIPs) to the ischemic myocardium. The cT-21-LIPs exhibited enhanced targeting efficiency to hypoxia primary cardiomyocytes in vitro and improved accumulation in the ischemic heart of AMI rats after injection via the tail vein due to the specifical target to overexpressed troponin. The cT-21-LIPs could significantly improve the cardiac function and decrease the infarct size after AMI, while maintaining the viability of cardiomyocytes. This design provides a novel strategy for delivering small nucleotide drugs specifically to the infarcted heart, which may find great potential in clinics.