Custom Cerium Oxide Nanoparticles Protect against a Free Radical Mediated Autoimmune Degenerative Disease in the Brain

被引：256

作者：

Heckman, Karin L. ^{[1
]}

DeCoteau, William ^{[2
]}

Estevez, Ana ^{[1
]}

Reed, Kenneth J. ^{[3
]}

Costanzo, Wendi ^{[3
]}

Sanford, David ^{[3
]}

Leiter, James C. ^{[4
]}

Clauss, Jennifer ^{[1
]}

Knapp, Kylie ^{[1
]}

Gomez, Carlos ^{[1
]}

Mullen, Patrick ^{[1
]}

Rathbun, Elle ^{[1
]}

Prime, Kelly ^{[1
]}

Marini, Jessica ^{[1
]}

Patchefsky, Jamie ^{[1
]}

Patchefsky, Arthur S. ^{[5
]}

Hailstone, Richard K. ^{[6
]}

Erlichman, Joseph S. ^{[1
]}

机构：

[1] St Lawrence Univ, Dept Biol, Canton, NY 13617 USA

[2] St Lawrence Univ, Dept Psychol, Canton, NY 13617 USA

[3] Cer Enterprises LLC, Rochester, NY 14610 USA

[4] Geisel Sch Med Dartmouth, Dept Physiol & Neurobiol, Lebanon, NH 03756 USA

[5] Temple Hlth, Dept Pathol, Fox Chase Med Ctr, Philadelphia, PA 19111 USA

[6] Rochester Inst Technol, Chester F Carlson Ctr Imaging Sci, Rochester, NY 14623 USA

来源：

ACS NANO | 2013年 / 7卷 / 12期

关键词：

nanoparticles; free radicals; experimental autoimmune encephalitis; tissue distribution; blood brain barrier; TARGETED DRUG-DELIVERY; RAT SPINAL-CORD; MULTIPLE-SCLEROSIS; POLYMERIC NANOPARTICLES; OXYGEN VACANCIES; DIFFERENT SIZES; CELLULAR UPTAKE; SLICE MODEL; LIFE-SPAN; PLASMA;

D O I：

10.1021/nn403743b

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

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 similar to 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.

引用

页码：10582 / 10596

页数：15

共 79 条

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