Perfluoropentane-based oxygen-loaded nanodroplets reduce microglial activation through metabolic reprogramming  

作　　者：Wanxian Luo Chuanhui Xu Linxi Li Yunxiang Ji Yezhong Wang Yingjia Li Yongyi Ye 

机构地区：[1]Department of Medicine Ultrasonics,Nanfang Hospital,Southern Medical University,Guangzhou,Guangdong Province,China [2]Institute of Neuroscience,Department of Neurosurgery,The Second Affiliated Hospital of Guangzhou Medical University,Guangzhou,Guangdong Province,China

出　　处：《Neural Regeneration Research》2025年第4期1178-1191,共14页中国神经再生研究（英文版）

基　　金：supported by the National Natural Science Foundation of China,No.82101327(to YY);President Foundation of Nanfang Hospital,Southern Medical University,No.2020A001(to WL);Guangdong Basic and Applied Basic Research Foundation,Nos.2019A1515110150,2022A1515012362(both to YY);Guangzhou Science and Technology Project,No.202201020111(to YY).

摘　　要：Microglia,the primary immune cells within the brain,have gained recognition as a promising therapeutic target for managing neurodegenerative diseases within the central nervous system,including Parkinson’s disease.Nanoscale perfluorocarbon droplets have been reported to not only possess a high oxygen-carrying capacity,but also exhibit remarkable anti-inflammatory properties.However,the role of perfluoropentane in microglia-mediated central inflammatory reactions remains poorly understood.In this study,we developed perfluoropentane-based oxygen-loaded nanodroplets(PFP-OLNDs)and found that pretreatment with these droplets suppressed the lipopolysaccharide-induced activation of M1-type microglia in vitro and in vivo,and suppressed microglial activation in a mouse model of Parkinson’s disease.Microglial suppression led to a reduction in the inflammatory response,oxidative stress,and cell migration capacity in vitro.Consequently,the neurotoxic effects were mitigated,which alleviated neuronal degeneration.Additionally,ultrahigh-performance liquid chromatography–tandem mass spectrometry showed that the anti-inflammatory effects of PFP-OLNDs mainly resulted from the modulation of microglial metabolic reprogramming.We further showed that PFP-OLNDs regulated microglial metabolic reprogramming through the AKT-mTOR-HIF-1αpathway.Collectively,our findings suggest that the novel PFP-OLNDs constructed in this study alleviate microglia-mediated central inflammatory reactions through metabolic reprogramming.

关 键 词：metabolic reprogramming microglia microglial migration nanotherapy neurodegenerative diseases NEUROINFLAMMATION oxygen-loaded nanodroplets Parkinson’s disease perfluoropentane ultra-performance liquid chromatography–mass spectrometry 

分 类 号：R741[医药卫生—神经病学与精神病学]