The Antioxidant Activity of Cerium Oxide Nanoparticles is Size Dependant and Blocks Aβ 1‐42 ‐Induced Free Radical Production and Neurotoxicity

We have demonstrated that a single 10 nM dose of cerium oxide nanoparticles (CeONP) with an average size of 10 nm, extends the lifespan & preserves neuronal function in brain cell cultures. We hypothesize that CeONP act as regenerative free radical scavengers. Here, we investigated the antioxidant activity of CeONP using EPR. Hydroxyl radicals ( . OH) were generated via Fenton's reaction. Superoxide radicals (O 2 .– ) were generated by irradiating a solution of riboflavin and DMPO with UV rays. CeONP (10 nm) completely quenched . OH & O 2 .– formation. CeONP with a particle size of 7 nm were less effective than 10 nm particles. We also examined the effect of Fe‐doped ceria (6% Fe), which was less effective than CeONP. The toxic fragment of Αβ, Αβ 1‐42 , produces free radicals & is hypothesized to be a contributory factor in Alzheimer's pathology. When incubated with spin trap Αβ 1‐42 (1mg/ml) generated a 6 line EPR spectra. Αβ 1‐42 –induced free radical production was completely blocked by CeONP (10 nm). We also examined the neuroprotective capacity of the 3 groups of CeONP using UV, H 2 O 2 , & Αβ 1‐42 challenge. In comparison to 7 nm CeONP, cell death induced by UV & H 2 O 2 was reduced more effectively by 10 nm CeONP, whereas Fe‐doping of CeONP abrogated antioxidant protection. Neuronal death associated with Αβ 1‐42 was reduced 65% by CEONP (10 nm). Our results suggest that 1) CeONP exhibit potent antioxidant activity, which is dependent on size, composition, & particle surface area and 2) CeONP protect neurons from free radical damage & Αβ 1‐42 toxicity.