Antioxidant activity and toxicity study of cerium oxide nanoparticles\n stabilized with innovative functional copolymers

Abstract

Oxidative stress, which is one of the main harmful mechanisms of pathologies\nincluding is-chemic stroke, contributes to both neurons and endothelial cell\ndamages, leading to vascular lesions. Although many antioxidants have been\ntested in preclinical studies, no treatment is currently available for stroke\npatients. Since cerium oxide nanoparticles (CNPs) exhibit remarkable\nantioxidant capacities, our objective is to develop an innovative coating to\nenhance CNPs biocompatibility without disrupting their antioxidant capacities\nor enhance their toxicity. This study reports the synthesis and\ncharacterization of functional polymers and their impact on the enzyme-like\ncatalytic activity of CNPs. To study the toxicity and the antioxidant\nproperties of CNPs for stroke and particularly endothelial damages, in vitro\nstudies are conducted on a cerebral endothelial cell line (bEnd.3). Despite\ntheir internalization in bEnd.3 cells, coated CNPs are devoid of cytotoxicity.\nMicroscopy studies report an intracellular localization of CNPs, more precisely\nin endosomes. All CNPs reduces glutamate-induced intracellular production of\nROS in endothelial cells but one CNP significantly reduces both the production\nof mitochondrial super-oxide anion and DNA oxidation. In vivo studies report a\nlack of toxicity in mice. This study there-fore describes and identifies\nbiocompatible CNPs with interesting antioxidant properties for ischemic stroke\nand related pathologies.\n