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

TL;DR

This study develops and characterizes innovative coated cerium oxide nanoparticles that exhibit strong antioxidant activity and low toxicity, showing potential for treating oxidative stress-related stroke damage.

Contribution

The paper introduces a novel functional polymer coating for cerium oxide nanoparticles that enhances biocompatibility without compromising their antioxidant properties.

Findings

Coated CNPs are non-toxic in vitro and in vivo.

CNPs reduce ROS production in endothelial cells.

One CNP significantly reduces mitochondrial super-oxide and DNA oxidation.

Abstract

Oxidative stress, which is one of the main harmful mechanisms of pathologies including is-chemic stroke, contributes to both neurons and endothelial cell damages, leading to vascular lesions. Although many antioxidants have been tested in preclinical studies, no treatment is currently available for stroke patients. Since cerium oxide nanoparticles (CNPs) exhibit remarkable antioxidant capacities, our objective is to develop an innovative coating to enhance CNPs biocompatibility without disrupting their antioxidant capacities or enhance their toxicity. This study reports the synthesis and characterization of functional polymers and their impact on the enzyme-like catalytic activity of CNPs. To study the toxicity and the antioxidant properties of CNPs for stroke and particularly endothelial damages, in vitro studies are conducted on a cerebral endothelial cell line (bEnd.3). Despite their internalization in bEnd.3 cells, coated CNPs are devoid of cytotoxicity. Microscopy studies report an intracellular localization of CNPs, more precisely in endosomes. All CNPs reduces glutamate-induced intracellular production of ROS in endothelial cells but one CNP significantly reduces both the production of mitochondrial super-oxide anion and DNA oxidation. In vivo studies report a lack of toxicity in mice. This study there-fore describes and identifies biocompatible CNPs with interesting antioxidant properties for ischemic stroke and related pathologies.