Mitochondria-Targeting Ceria Nanoparticles as Antioxidants for Alzheimer’s Disease

• Published in: ACS nano 2016-02, Vol.10 (2), p.2860-2870
• Main Authors: Kwon, Hyek Jin, Cha, Moon-Yong, Kim, Dokyoon, Kim, Dong Kyu, Soh, Min, Shin, Kwangsoo, Hyeon, Taeghwan, Mook-Jung, Inhee
• Format: Article
• Language: English
• Subjects: Alzheimer Disease - drug therapy; Animals; Antioxidants - administration & dosage; Antioxidants - pharmacology; Antioxidants - therapeutic use; Cerium - administration & dosage; Cerium - pharmacology; Cerium - therapeutic use; HeLa Cells; Humans; Metal Nanoparticles - chemistry; Mice; Mitochondria - drug effects; Mitochondria - metabolism; Organophosphorus Compounds - chemistry; Oxidative Stress
• ISSN: 1936-0851; 1936-086X
• DOI: 10.1021/acsnano.5b08045

Mitochondrial oxidative stress is a key pathologic factor in neurodegenerative diseases, including Alzheimer’s disease. Abnormal generation of reactive oxygen species (ROS), resulting from mitochondrial dysfunction, can lead to neuronal cell death. Ceria (CeO2) nanoparticles are known to function as strong and recyclable ROS scavengers by shuttling between Ce3+ and Ce4+ oxidation states. Consequently, targeting ceria nanoparticles selectively to mitochondria might be a promising therapeutic approach for neurodegenerative diseases. Here, we report the design and synthesis of triphenylphosphonium-conjugated ceria nanoparticles that localize to mitochondria and suppress neuronal death in a 5XFAD transgenic Alzheimer’s disease mouse model. The triphenylphosphonium-conjugated ceria nanoparticles mitigate reactive gliosis and morphological mitochondria damage observed in these mice. Altogether, our data indicate that the triphenylphosphonium-conjugated ceria nanoparticles are a potential therapeutic candidate for mitochondrial oxidative stress in Alzheimer’s disease.