神经炎症
免疫系统
小胶质细胞
炎症
黑质
细胞生物学
胞外囊泡
趋化因子
神经科学
化学
免疫学
生物
生物化学
微泡
多巴胺
多巴胺能
小RNA
基因
作者
Chuan Zhang,Zhiqiang Zhang,Hao Yuan,Ru Xiao,Ya-Ru Zhang,Wei Chen,Xiong Ni,Ning He,Guangliang Chen,Shuangying Gui,Zitong Cheng,Qi Wang
出处
期刊:ACS Nano
[American Chemical Society]
日期:2024-08-15
标识
DOI:10.1021/acsnano.4c04674
摘要
Although conventional intervention to microglia can mitigate neuroinflammation in the short term, immune disorders by peripheral inflammatory cells can infiltrate continuously, resulting in an overactivated immune microenvironment of Parkinson's disease (PD). Here, we design engineered extracellular vesicle-based nanoformulations (EVNs) to address multiple factors for the management of PD. Specifically, EVN is developed by coating CCR2-enriched mesenchymal stem cell-derived extracellular vesicles (MSCCCR2 EVs) onto a dihydrotanshinone I-loaded nanocarrier (MSeN-DT). The MSCCCR2 EVs (the shell of EVN) can actively show homing to specific chemokines CCL2 in the substantia nigra, which enables them to block the infiltration of peripheral inflammatory cells. Interestingly, MSeN-DT (the core of EVN) can promote the Nrf2–GPX4 pathway for the suppression of the source of inflammation by inhibiting ferroptosis in microglia. In the PD model mice, a satisfactory therapeutic effect is achieved, with inhibition of peripheral inflammatory cell infiltration, precise regulation of inflammatory microglia in the substantia nigra, as well as promotion of behavioral improvement and repairing damaged neurons. In this way, the combinatorial code of alleviation of inflammation and modulation of immune homeostasis can reshape the immune microenvironment in PD, which bridges internal anti-inflammatory and external immunity. This finding reveals a comprehensive therapeutic paradigm for PD that breaks the vicious cycle of immune overactivation.
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