nn5b08045_si_001.pdf (4.52 MB)
Mitochondria-Targeting Ceria Nanoparticles as Antioxidants for Alzheimer’s Disease
journal contribution
posted on 2016-02-04, 00:00 authored by Hyek Jin Kwon, Moon-Yong Cha, Dokyoon Kim, Dong Kyu Kim, Min Soh, Kwangsoo Shin, Taeghwan Hyeon, Inhee Mook-JungMitochondrial 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.