In this study we have found that cerium oxide nanoparticles exhibit catalase mimetic activity. Surprisingly, the catalase mimetic activity correlates with a reduced level of cerium in the +3 state, in contrast to the relationship between surface charge and superoxide scavenging properties.

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 it is 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 analysis 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. IntroductionCerium is a lanthanide series rare earth element, and is the most abundant of these rare earths, present at about 66 parts per million in the earth's crust. Cerium can exist in either the free metal or oxide form, and can cycle between the cerous, cerium (III), and ceric, cerium (IV), oxidation states [1]. Both oxidation states of cerium strongly absorb ultraviolet light and have two characteristic spectrophotometric absorbance peaks. The first peak is in the 230 to 260 nm range and corresponds to cerium (III) absorbance. The second peak absorbance occurs in the 300 to 400 nm range and corresponds to cerium (IV) absorbance [2]. Nanoceria has similar chemical and physical properties to bulk cerium, however, because of the increased surface area and oxygen vacancies present, nanoceria has potential as a unique catalyst [3]. Much of the unusual catalytic chemistry involved with nanoceria is believed to be due to oxygen vacancy sites at the surface of the nanoceria lattice. These oxygen vacancies are characterized by cerium (III) atoms in the center of the vacancy surrounded by adjacent cerium (IV) atoms [4]. The presence of cerium (III) at the surface of nanoceria is unique to the center * To whom correspondence is requested, W. T. Self wself@mail.ucf.edu; fax (407) 823-0956. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Current research using nanoceria as a catalyst is quite broad. Among other applications, nanoceria is being d...

The valence and oxygen defect properties of cerium oxide nanoparticles (nanoceria) suggest that they may act as auto-regenerative free radical scavengers. Overproduction of the free radical nitric oxide (NO) by the enzyme inducible nitric oxide synthase (iNOS) has been implicated as a critical mediator of inflammation. NO is correlated with disease activity and contributes to tissue destruction. The ability of nanoceria to scavenge free radicals, or reactive oxygen species (ROS), and inhibit inflammatory mediator production in J774A.1 murine macrophages is investigated. Cells internalize nanoceria, the treatment is nontoxic, and oxidative stress and pro-inflammatory iNOS protein expression are abated with stimulation. In vivo studies show nanoceria deposition in mouse tissues with no pathogenicity. Taken together, it is suggested that cerium oxide nanoparticles are well tolerated in mice and are incorporated into cellular tissues. Furthermore, nanoceria may have the potential to reduce ROS production in states of inflammation and therefore serve as a novel therapy for chronic inflammation.