A Redox Modulatory Sod Mimetic Nanozyme Prevents The Formation of Cytotoxic Peroxynitrite And Improves Nitric Oxide Bioavailability in Human Endothelial Cells.

The endothelium-derived signaling molecule nitric oxide (NO) in addition to controlling multifarious servo-regulatory functions in the vasculature, 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-rich environment has emerged as a major reason for the reduced NO levels in the vascular wall, leading to endothelial dysfunction, atherosclerosis, and other cardiovascular complications. However, it is a challenge to design SOD mimetics that can selectively catalyze the dismutation of superoxide in the presence of NO, considering their rapid reaction. Herein, we report that the SOD mimetic CeVO nanozymes effectively regulate the bioavailability of both NO and superoxide, the two key constitutive molecules of vascular endothelium, even in the absence of the cellular SOD enzyme. The nanozymes optimally modulate the amount of superoxide in the cells under oxidative stress conditions and improve the endogenously generated NO levels by preventing the formation of peroxynitrite. Also, the nanoparticles internalize into the cells via clathrin-mediated endocytosis and the cellular uptake depends both on the size- and morphology of the nanozymes. When administered intravenously to mice, the CeVO nanozymes caused no definite organ toxicity and the haematological and biochemical parameters remained unchanged, indicating their biosafety and potential use in biological applications. This article is protected by copyright. All rights reserved.