Ceria is a lanthanide series element that can exist as Ce3+ or Ce4+. Cerium oxide nanostructures are being developed for use in industry as catalysts. Nanostructures often behave differently from their corresponding macrostructures and these new behaviors can result in novel and important biological and chemical properties. The free radical theory of aging suggests that free radicals many of which are reactive oxygen species, damage cellular macromolecules. This damage can contribute to degenerative diseases, cancer and aging. Recent research has shown that ceria oxide nanoparticles protected cells from UV and radiation damage as well as decrease intracellular reactive oxygen species in primary cell cultures. The enzyme superoxide dismutase (SOD) protects the cell from free radicals by reacting with superoxide, a reactive oxygen species. Chemicals that catalyze the same reaction as SOD are referred to as SOD mimetics. Another biologically significant free radical is nitric oxide, a reactive nitrogen species. Nitric oxide is an important signaling molecule in both the cardiovascular and nervous system; however it can also cause damage to proteins through nitrosylation. When superoxide and nitric oxide react with each other they form the highly potent free radical, peroxynitrite. This reaction naturally occurs in the phagolysosome of the macrophage and is utilized by the immune system to kill pathogens. Nanoceria was tested for activity against superoxide, nitric oxide and peroxynitrite. The results presented in this work show that ceria oxide nanoparticles exhibit SOD mimetic activity and reduce protein nitrosylation in vitro.

Cerium is the most abundant of the rare earth metals, found on average at a level of 66 parts per million in the earth's crust. The unique redox properties of cerium and cerium oxide nanoparticles have led to its use in a wide variety of industrial and commercial uses such as oxygen sensors, fertilizers and as a catalyst to remove toxic gases in automobile exhaust. The use of cerium has also garnered interest in the nanotechnology field. Nanoceria has been generated in its oxide form as nanoparticles and nanorods. Recently, nanoceria has been shown to protect against oxidative stress in both animal and cell culture models. Although not fully understood, this observed protective effect of nanoceria is believed to be the result of recently identified SOD mimetic activity. Currently there is little understanding as to how nanoceria is capable of scavenging radicals or what properties makes nanoceria an effective SOD mimetic. Our data shows strong evidence that the oxidation state of nanoceria is directly related to its reported SOD mimetic activity. As such, future studies of nanoceria should be mindful of the oxidation state of nanoceria preparations as only nanoceria with a high concentration of cerium (III) have shown effective SOD mimetic activity. In addition to the characterization of nanoceria and its SOD mimetic activity, we have evidence that free cerium is capable of generating radicals and damaging DNA in vitro in the presence of hydrogen peroxide. These data strongly suggests that the rare earth inner-transition metal cerium is capable of generating hydroxyl radicals via a Fenton-like reaction. Based on these results the use of free cerium salts should be monitored to limit environmental exposure to cerium. Altogether our data would suggest that cerium by virtue of its unique redox chemistry is quite capable of accepting and donating electrons from its surroundings. In its free form cerium is able to redox cycle easily and can generate radicals. However, paradoxically nanoceria may not easily redox cycle due to the bound lattice structure of the particle. The unique nature of nanoceria and cerium leads to a unique circumstance where nanoceria is a radical scavenger while free cerium generates radicals. As such, further investigation is needed to insure that leeching or cerium from nanoceria does not abrogate any potential benefit nanoceria may provide.