A Redox Modulatory SOD Mimetic Nanozyme Prevents the Formation of Cytotoxic Peroxynitrite and Improves Nitric Oxide Bioavailability in Human Endothelial Cells

Abstract

AbstractThe endothelium‐derived signalling molecule nitric oxide (NO) in addition to controlling multifarious servo‐regulatory functions, suppresses key processes in vascular lesion formation and prevents atherogenesis and other vascular abnormalities. The conversion of NO into cytotoxic and powerful oxidant peroxynitrite (ONOO−) in a superoxide (O2.−)‐rich environment has emerged as a major reason for reduced NO levels in vascular walls, leading to endothelial dysfunction and cardiovascular complications. So, designing superoxide dismutase (SOD) mimetics that can selectively catalyze the dismutation of O2.− in the presence of NO, considering their rapid reaction is challenging and is of therapeutic relevance. Herein, the authors report that SOD mimetic cerium vanadate (CeVO4) nanozymes effectively regulate the bioavailability of both NO and O2.−, the two vital constitutive molecules of vascular endothelium, even in the absence of cellular SOD enzyme. The nanozymes optimally modulate the O2.− level in endothelial cells under oxidative stress conditions and improve endogenously generated NO levels by preventing the formation of ONOO−. Furthermore, nanoparticles exhibit size‐ and morphology‐dependent uptake into the cells and internalize via the clathrin‐mediated endocytosis pathway. Intravenous administration of CeVO4 nanoparticles in mice caused no definite organ toxicity and unaltered haematological and biochemical parameters, indicating their biosafety and potential use in biological applications.