Advances in the Study of Cerium Oxide Nanoparticles: New Insights into Antiamyloidogenic Activity.

There seems to be general agreement that oxidative stress is involved in many pathological conditions including Parkinson's, Alzheimer's, and other neurodegenerative diseases, and overall aging. Cerium oxide nanoparticles, also known as nanoceria (CeO 2 -NPs), have shown promise as catalytic antioxidants, based on their ability to switch between Ce 3+ and Ce 4+ valence states. In the present work we have synthesized and characterized CeO 2 -NPs, examined the effect of CeO 2 -NPs on amyloidogenesis of insulin, and analyzed the impact of CeO 2 -NPs on oxidative stress and biocompatibility in vitro in three types of invasive cancer cells, and in vivo in the preclinical model of the chorioallantoic membrane (CAM) of quail embryos. The different experimental techniques revealed a high stability and homogeneity of the "naked" CeO 2 -NPs synthesized by precipitation from a reversal microemulsion. The CeO 2 -NPs were 5-6 nm in diameter (TEM) and monodispersed and have a ζ +46.9 mV ζ potential in Milli-Q water. We demonstrated for the first time that CeO 2 -NPs affect insulin fibrillation in a dose-dependent manner. The inhibiting, IC 50 , and disassembling, DC 50 , concentrations were calculated to be ∼100 ± 3.5 and ∼200 ± 5.5 μg/mL, respectively. Furthermore, CeO 2 -NPs demonstrated reliable biocompatibility and sufficient uptake by glioma and breast cancer cells. The presence of a high concentration of CeO 2 -NPs within the cells resulted only in local changes in metabolic activity and generation of oxidative stress at a low level. Moreover, high biocompatibility with CeO 2 -NPs was shown in vivo in the CAM.