N-acetyl-L-cysteine-modified macrophage membrane-coated VEGF sustained-release nanoparticles for treatment of myocardial infarction: A biomimetic nano-buffer for neutralization of detrimental factors and promotion of mature angiogenesis

Myocardial infarction (MI) is a severe cardiovascular event arising from vascular thrombosis, causing cardiomyocyte fatality. Neovascularization, facilitated by Vascular Endothelial Growth Factor (VEGF), is a crucial therapy that delivers oxygen and nutrients to the surviving myocardium. After MI, a substantial influx of macrophages of the inflammatory phenotype infiltrates the infarcted myocardium. these macrophages secrete factors that exacerbate myocardial injury and orchestrate neovascular regression. A biomimetic nano-buffer system was developed in this study, consisting of VEGF-encapsulated nanoparticles coated with N-acetyl-L-cysteine (NAC)-modified macrophage membrane. These nanoparticles accumulate at the infarcted myocardium by exploiting the macrophage membrane's biomimetic inflammation chemotaxis. It effectively neutralizes detrimental factors in the infarcted myocardium while simultaneously enabling the controlled release of VEGF nanoparticles to promote angiogenesis within the affected tissue. What sets our research apart is the profound impact of the nano-buffer on macrophages, accomplished by its efficient scavenging of reactive oxygen species. This action triggers a vital response—the secretion of PDGF by macrophages—which significantly enhances the maturation of nascent blood vessels. The cumulative effect of these actions creates an exceptionally favorable milieu, fostering neovascularization. This study highlights the potential of the nano-buffer system in treating MI.