Platelet Membrane-Camouflaged Nanoparticles Carry microRNA inhibitor Against Myocardial Ischemia-Reperfusion Injury

Abstract Background The incidence of myocardial ischemia reperfusion injury (MIRI) is increasing year by year, and there is an urgent need to develop new treatment methods. Nrf2 is believed to play a protective role during MIRI and is regulated by microRNAs (miRNAs). Platelets are physiologically targeted to MIRI injury sites. The focus of this study is on platelet membranes, also called platelet membrane vesicles (PMVs), camouflaged PLGA nanoparticles, carrying microRNA inhibitors to regulate Nrf2, and play a therapeutic role during MIRI. Results First, we characterized the high transfection efficiency and low toxicity of PLGA in vitro, as well as the good targeting of PMVs in vivo; then, we found a microRNA (microRNA-155-5p) that effectively regulates Nrf2 in vitro, and confirmed its effect on cardiomyocyte apoptosis during MIRI; finally, PMVs camouflaged PLGA-miRNA complexes (PMVs@PLGA-miRNA complexes) were prepared and applied to MIRI treatment, and it was found that it can significantly alleviate the myocardial damage caused by MIRI in vivo and exert effective therapeutic effects. Conclusions This research has developed a PMVs camouflaged PLGA nanoparticles, which can carry microRNA inhibitors (PMVs@PLGA-miRNA complexes), which can be targeted and efficiently transfected into cardiomyocytes, and play an important role in the treatment of MIRI. Our results suggest a novel biological delivery system that targets M​​IRI.