Mitochondria-Targeting Ceria Nanoparticles as Antioxidants for Alzheimeŕs Disease

Hyek Jin Kwon, Moon Yong Cha, Dokyoon Kim, Dong Kyu Kim, Min Soh, Kwangsoo Shin, Taeghwan Hyeon, Inhee Mook-Jung

Research output: Contribution to journalArticlepeer-review

522 Scopus citations

Abstract

Mitochondrial oxidative stress is a key pathologic factor in neurodegenerative diseases, including Alzheimeŕs 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 Alzheimeŕs 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 Alzheimeŕs disease.

Original languageEnglish
Pages (from-to)2860-2870
Number of pages11
JournalACS Nano
Volume10
Issue number2
DOIs
StatePublished - 23 Feb 2016
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2016 American Chemical Society.

Keywords

  • Alzheimeŕs disease
  • ceria nanoparticles
  • mitochondria
  • reactive oxygen species
  • therapeutic agents

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