Custom-Made Ceria Nanoparticles Show a Neuroprotective Effect by Modulating Phenotypic Polarization of the Microglia
Custom-Made Ceria Nanoparticles Show a Neuroprotective Effect by Modulating Phenotypic Polarization of the Microglia
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定制的二氧化铈纳米颗粒通过调节小胶质细胞的表型极化显示出神经保护作用
DOI：
10.1002/anie.201802309
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发表时间：
2018
期刊：
影响因子：
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通讯作者：
Li Cong
中科院分区：
文献类型：
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作者：
Zeng Feng;Wu Yingwei;Li Xinwei;Ge Xiaojiao;Guo Qinghua;Lou Xiaobing;Cao Zhonglian;Hu Bingwen;Long Nicholas J;Mao Ying;Li Cong
二氧化铈纳米颗粒在脑疾病背景下的神经保护作用已经通过其抗氧化作用来解释。然而，其深层机制仍然未知。作为大脑中的常驻免疫细胞，小胶质细胞对应激刺激产生多种功能重编程，称为极化。在此，开发了定制的二氧化铈纳米颗粒，并发现其以极高的效率吸收多种活性氧。这些纳米颗粒在病理条件下驱动小胶质细胞从促炎表型极化为抗炎表型。这些纳米颗粒的预处理通过阻断促炎信号传导将小胶质细胞功能从有害改变为对神经元细胞的保护。这项工作不仅有助于阐明二氧化铈纳米颗粒介导的神经保护机制，而且还提供了一种新的策略，通过切换小胶质细胞表型激活的平衡来重新平衡免疫环境。
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.