Engineered macrophage membrane-enveloped nanomedicine for ameliorating myocardial infarction in a mouse model

Myocardial infarction (MI) is the serious condition causing lots of death over the world. Myocytes apoptosis, inflammation, and fibrosis are three important factors implicated in pathogenesis of MI. Targeting these three factors has been shown to ameliorate MI and rescue cardiac function. Previous studies have demonstrated that microRNA (miR) 199a-3p protect against MI. In this study, we prepare macrophage membrane coated nanoparticles (MMNPs) containing miR199a-3p. We evaluate the effects of these NPs on apoptosis and cell proliferation in vitro and the effects on inflammation cytokine production, expression of fibrosis related proteins, cardiac injuries, and functions in MI mice. We find that the MMNPs have receptors of interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF-alpha) and can bind to these cytokines. MMNPs prevent hypoxia-induced apoptosis and promote cell proliferation, suppress the inflammation, and inhibit the cardiac fibrosis in MI mice. These results demonstrate that MMNPs ameliorate left ventricular remodeling and cardiac functions, and protect against MI, suggesting MMNPs containing miR199a-3p is a potential therapeutic approach to treat MI.