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

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• 作者：Hyek Jin Kwon ; Moon-Yong Cha ; Dokyoon Kim ; Dong Kyu Kim ; Min Soh ; Kwangsoo Shin ; Taeghwan Hyeon ; Inhee Mook-Jung
• 刊名：ACS Nano
• 出版年：2016
• 出版时间：February 23, 2016
• 年：2016
• 卷：10
• 期：2
• 页码：2860-2870
• 全文大小：666K
• ISSN：1936-086X

文摘

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.