The role of cerium redox state in the SOD mimetic activity of nanoceria.

Cerium oxide nanoparticles (nanoceria) have recently been shown to protect cells against oxidative stress in both cell culture and animal models. Nanoceria has been shown to exhibit superoxide dismutase (SOD) activity using a ferricytochrome C assay, and this mimetic activity that has been postulated to be responsible for cellular protection by nanoceria. The nature of nanoceria's antioxidant properties, specifically what physical characteristics make nanoceria effective at scavenging superoxide anion, is poorly understood. In this study electron paramagnetic resonance (EPR) analysis confirms the reactivity of nanoceria as an SOD mimetic. X-ray photoelectron spectroscopy (XPS) and UV-visible analyses of nanoceria treated with hydrogen peroxide demonstrate that a decrease in the Ce 3(+)/4(+) ratio correlates directly with a loss of SOD mimetic activity. These results strongly suggest that the surface oxidation state of nanoceria plays an integral role in the SOD mimetic activity of nanoceria and that ability of nanoceria to scavenge superoxide is directly related to cerium(III) concentrations at the surface of the particle.

Fenton-like reaction catalyzed by the rare earth inner transition metal cerium.

Cerium (Ce) is a rare earth metal that is not known to have any biological role. Cerium oxide materials of several sizes and shapes have been developed in recent years as a scaffold for catalysts. Indeed even cerium oxide nanoparticles themselves have displayed catalytic activities and antioxidant properties in tissue culture and animal models. Because of ceria's ability to cycle between the +3 and +4 states at oxygen vacancy sites, we investigated whether cerium metal would catalyze a Fenton-like reaction with hydrogen peroxide. Indeed, cerium chloride did exhibit radical production in the presence of hydrogen peroxide, as assessed by relaxation of supercoiled plasmid DNA. Radical production in this reaction was also followed by production of radical cation of 2,2'-azinobis-(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS). Radical scavengers and spin traps were capable of competing with ABTS for radicals produced in this cerium dependent Fenton-like reaction. Electron paramagnetic resonance experiments reveal both hydroxyl radical and superoxide anion in a reaction containing cerium and hydrogen peroxide. Based on these results we propose that cerium is capable of redox-cycling with peroxide to generate damaging oxygen radicals.