Antioxidant Activity and Toxicity Study of Cerium Oxide Nanoparticles Stabilized with Innovative Functional Copolymers

Abstract

Oxidative stress, which is one of the main harmful mechanisms of pathologies including ischemic stroke, contributes to both neurons and endothelial cell damages, leading to vascular lesions. Although many antioxidants are tested in preclinical studies, no treatment is currently available for stroke patients. Since cerium oxide nanoparticles (CNPs) exhibit remarkable antioxidant capacities, the 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 reactive oxygen species (ROS) in endothelial cells but one CNP significantly reduces both the production of mitochondrial superoxide anion and DNA oxidation. In vivo studies report a lack of toxicity in mice. This study therefore describes and identifies biocompatible CNPs with interesting antioxidant properties for ischemic stroke and related pathologies.

Preparation, Characterization and Multiple Biological Properties of Peptide-Modified Cerium Oxide Nanoparticles

“…The CAT activity of cerium oxide nanoparticles was measured by monitoring the generated O 2 content from the decomposition of H 2 O 2 using a dissolved oxygen electrode (JPSJ-605F, Lei ci, Shanghai, China) according to the previously reported literature [ 39 , 40 ]. Briefly, nanoparticles (500 µL, 10 mg/mL, calculated as Ce) were added into 8 mL of Tris-Cl buffer (pH = 7.48), and then 500 µL of H 2 O 2 (30%) solution was added into the solution.…”

Versatile Coating Platform for Metal Oxide Nanoparticles: Applications to Materials and Biological Science

“…2d) containing an amine-terminated PEG allowing subsequent chemcial conjugation. 109 Fig. 8b and Fig.…”

“…The CeO2 and 𝛾-Fe2O3 NPs have diameters of 7.8 nm and 13.2 nm and are those already discussed in Section II.1.For these particles, 1 pg of metal corresponds to 2.5×106 and 5×104 NP units, respectively. As coatings, we used citrate ions, poly(acylic acid) of 𝑀 𝑤 = 5 kDa, and two phosphonic acid PEG copolymers, (MPEG2k)3-co-MPh3 of 𝑀 𝑤 = 13 kDa75 and (MPEG2k)5-co-MPh5 of 𝑀 𝑤 = 20 kDa109 The straight thick lines in each figure depict the maximum amount of MOx-NPs taken up by a single cell. Adapted with permission from Ref 109.…”

Nanomaterials alleviating redox stress in neurological diseases: mechanisms and applications

“…Most evaluations of the biocompatibility and cytotoxicity of CeO 2 NPs found no toxicity, either in vivo or in vitro [ 56 ]. The onset of toxicity usually occurred after a high-dose treatment.…”

“…The onset of toxicity usually occurred after a high-dose treatment. Toxicity was observed after injection of CeO 2 NPs at doses of > 250 mg/kg or inhalation of 641 mg/m 3 , whereas they were nontoxic at doses of 0.5 ~ 100 mg/kg for 24 h given over 1 month [ 56 – 58 ]. Even so, the biosafety of CeO 2 NPs still needs to be carefully evaluated before clinical application.…”