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

The 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.