Journal
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
Volume 57, Issue 20, Pages 5808-5812Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/anie.201802309
Keywords
central nervous system; cerium; immunotherapy; microglia; nanoparticles
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Funding
- National Basic Research Program of China (973 Program) [2015CB755500]
- National Natural Science Foundation of China [81571741, 81771895, 81572483, 81611130223, 21522303]
- Shanghai Foundation for Development of Science and Technology [15140901300]
- Shanghai Science and Technology Committee [13411950201, 16JC1420100]
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The neuroprotective effect of ceria nanoparticles in the context of brain disorders has been explained by their antioxidant effect. However, the in-depth mechanism remains unknown. As resident immune cells in the brain, microglia exert a variety of functional reprogramming termed as polarization in response to stress stimuli. Herein, custom-made ceria nanoparticles were developed and found to scavenge multiple reactive oxygen species with extremely high efficiency. These nanoparticles drove microglial polarization from a pro-inflammatory phenotype to an anti-inflammatory phenotype under pathological conditions. Pretreatment of these nanoparticles changed the microglial function from detrimental to protective for the neuronal cells by blocking the pro-inflammatory signaling. This work not only helps to elucidate the mechanism of ceria-nanoparticle-mediated neuroprotection but also provides a new strategy to rebalance the immuno-environment by switching the equilibrium of the phenotypic activation of microglia.
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