title: Custom cerium oxide nanoparticles protect against a free radical mediated autoimmune degenerative disease in the brain.
abstract: Cerium oxide nanoparticles are potent antioxidants, based on their ability to either donate or receive electrons as they alternate between the +3 and +4 valence states. The dual oxidation state of ceria has made it an ideal catalyst in industrial applications, and more recently, nanoceria's efficacy in neutralizing biologically generated free radicals has been explored in biological applications. Here, we report the in vivo characteristics of custom-synthesized cerium oxide nanoparticles (CeNPs) in an animal model of immunological and free-radical mediated oxidative injury leading to neurodegenerative disease. The CeNPs are 2.9 nm in diameter, monodispersed and have a -23.5 mV zeta potential when stabilized with citrate/EDTA. This stabilizer coating resists being 'washed' off in physiological salt solutions, and the CeNPs remain monodispersed for long durations in high ionic strength saline. The plasma half-life of the CeNPs is ∼4.0 h, far longer than previously described, stabilized ceria nanoparticles. When administered intravenously to mice, the CeNPs were well tolerated and taken up by the liver and spleen much less than previous nanoceria formulations. The CeNPs were also able to penetrate the brain, reduce reactive oxygen species levels, and alleviate clinical symptoms and motor deficits in mice with a murine model of multiple sclerosis. Thus, CeNPs may be useful in mitigating tissue damage arising from free radical accumulation in biological systems.
authors.affiliation: Departments of Biology and ‡Psychology, St. Lawrence University , Canton, New York 13617, United States.
authors.forename: Karin L
authors.initials: KL
authors.lastname: Heckman
authors.forename: William
authors.initials: W
authors.lastname: DeCoteau
authors.forename: Ana
authors.initials: A
authors.lastname: Estevez
authors.forename: Kenneth J
authors.initials: KJ
authors.lastname: Reed
authors.forename: Wendi
authors.initials: W
authors.lastname: Costanzo
authors.forename: David
authors.initials: D
authors.lastname: Sanford
authors.forename: James C
authors.initials: JC
authors.lastname: Leiter
authors.forename: Jennifer
authors.initials: J
authors.lastname: Clauss
authors.forename: Kylie
authors.initials: K
authors.lastname: Knapp
authors.forename: Carlos
authors.initials: C
authors.lastname: Gomez
authors.forename: Patrick
authors.initials: P
authors.lastname: Mullen
authors.forename: Elle
authors.initials: E
authors.lastname: Rathbun
authors.forename: Kelly
authors.initials: K
authors.lastname: Prime
authors.forename: Jessica
authors.initials: J
authors.lastname: Marini
authors.forename: Jamie
authors.initials: J
authors.lastname: Patchefsky
authors.forename: Arthur S
authors.initials: AS
authors.lastname: Patchefsky
authors.forename: Richard K
authors.initials: RK
authors.lastname: Hailstone
authors.forename: Joseph S
authors.initials: JS
authors.lastname: Erlichman
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000737:chemistry; D001327:Autoimmune Diseases / Q000188:drug therapy / Q000517:prevention & control*; D001812:Blood-Brain Barrier; D001921:Brain / Q000187:drug effects*; D002563:Cerium / Q000737:chemistry*; D004195:Disease Models, Animal; D004337:Drug Carriers; D005260:Female; D005609:Free Radicals; D007477:Ions; D008099:Liver / Q000187:drug effects; D053768:Metal Nanoparticles / Q000737:chemistry*; D051379:Mice; D008810:Mice, Inbred C57BL; D008833:Microcirculation; D009048:Motor Skills; D009103:Multiple Sclerosis / Q000188:drug therapy / Q000517:prevention & control; D050997:Nanomedicine; D019636:Neurodegenerative Diseases / Q000188:drug therapy / Q000517:prevention & control*; D018384:Oxidative Stress; D051381:Rats; D017207:Rats, Sprague-Dawley; D026361:Reactive Nitrogen Species; D017382:Reactive Oxygen Species; D013154:Spleen / Q000187:drug effects; D014018:Tissue Distribution
chemical_list: D000975:Antioxidants; D004337:Drug Carriers; D005609:Free Radicals; D007477:Ions; D026361:Reactive Nitrogen Species; D017382:Reactive Oxygen Species; D002563:Cerium; C030583:ceric oxide