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

Autor: Geethika M; Department of Inorganic and Physical Chemistry, Indian Institute of Science, Bangalore, 560012, India., Singh N; Department of Inorganic and Physical Chemistry, Indian Institute of Science, Bangalore, 560012, India., Kumar S; Department of Inorganic and Physical Chemistry, Indian Institute of Science, Bangalore, 560012, India., Kumar SKN; Department of Inorganic and Physical Chemistry, Indian Institute of Science, Bangalore, 560012, India., Mugesh G; Department of Inorganic and Physical Chemistry, Indian Institute of Science, Bangalore, 560012, India.
Jazyk: angličtina
Zdroj: Advanced healthcare materials [Adv Healthc Mater] 2023 Oct; Vol. 12 (27), pp. e2300621. Date of Electronic Publication: 2023 Aug 13.
DOI: 10.1002/adhm.202300621
Abstrakt: 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 (O 2 .- )-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 O 2 .- 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 (CeVO 4 ) nanozymes effectively regulate the bioavailability of both NO and O 2 .- , the two vital constitutive molecules of vascular endothelium, even in the absence of cellular SOD enzyme. The nanozymes optimally modulate the O 2 .- 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 CeVO 4 nanoparticles in mice caused no definite organ toxicity and unaltered haematological and biochemical parameters, indicating their biosafety and potential use in biological applications.
(© 2023 Wiley-VCH GmbH.)
Databáze: MEDLINE
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