Custom‐Made Ceria Nanoparticles Show a Neuroprotective Effect by Modulating Phenotypic Polarization of the Microglia

• Published in: Angewandte Chemie International Edition 2018-05, Vol.57 (20), p.5808-5812
• Main Authors: Zeng, Feng, Wu, Yingwei, Li, Xinwei, Ge, Xiaojiao, Guo, Qinghua, Lou, Xiaobing, Cao, Zhonglian, Hu, Bingwen, Long, Nicholas J., Mao, Ying, Li, Cong
• Format: Article
• Language: English
• Subjects: Animals; Antioxidants; Brain; Cell Survival - drug effects; central nervous system; cerium; Cerium oxides; Immune system; immunotherapy; Inflammation; Mice; Microglia; Microglia - drug effects; Microglia - immunology; Microglia - metabolism; Nanoparticles; Nanoparticles - chemistry; Neuroprotection; Neuroprotective Agents - chemistry; Neuroprotective Agents - pharmacology; Particle Size; Phenotype; Phenotypes; Polarization; Pretreatment; Reactive oxygen species; Reactive Oxygen Species - metabolism; Surface Properties
• ISSN: 1433-7851; 1521-3773
• DOI: 10.1002/anie.201802309

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. Remodeling the immuno‐environment in brain disorders: Custom‐made ceria nanoparticles (CeNP‐PEG) can simultaneously eradicate diverse reactive oxygen species (ROS) with high efficiency and velocity and shift microglial polarization from a pro‐inflammatory M1‐phenotype to an anti‐inflammatory M2‐phenotype after stress stimuli. In this way, the pro‐inflammatory signaling pathway in neuronal cells is blocked and the immuno‐environment is converted from detrimental to protective.