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

Neural Regeneration Research 2025年第4期20卷 1178-1191页

作者： Wanxian Luo Chuanhui Xu Linxi Li Yunxiang Ji Yezhong Wang Yingjia Li Yongyi Ye Department of Medicine Ultrasonics Nanfang HospitalSouthern Medical UniversityGuangzhouGuangdong ProvinceChina Institute of Neuroscience Department of NeurosurgeryThe Second Affiliated Hospital of Guangzhou Medical UniversityGuangzhouGuangdong ProvinceChina

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

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Tumor Microenvironment-Adaptive Nanoplatform Synergistically Enhances Cascaded Chemodynamic Therapy

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Bioactive Materials 2023年第4期22卷 239-253页

作者： Yuemin Wang Duan Wang Yuyue Zhang Hong Xu Luxuan Shen Jing Cheng Xinyuan Xu Hong Tan Xingyu Chen Jianshu Li College of Polymer Science and Engineering State Key Laboratory of Polymer Materials EngineeringSichuan UniversityChengdu610065China Orthopedic Research Institution Department of OrthopedicsWest China HospitalSichuan UniversityChengdu610041China College of Medicine Southwest Jiaotong UniversityChengdu610003China State Key Laboratory of Oral Diseases West China Hospital of StomatologyMed-X Center for MaterialsSichuan UniversityChengdu610041China

Chemodynamic therapy(CDT),a noninvasive strategy,has emerged as a promising alternative to conventional chemotherapy for treating tumors.However,its therapeutic effect is limited by the amount of H_(2)O_(2),pH value,the hypoxic environment of tumors,and it has suboptimal tumor-targeting ability.In this study,tumor cell membrane-camouflaged mesoporous Fe_(3)O_(4) nanoparticles loaded with perfluoropentane(PFP)and glucose oxidase(GOx)are used as a tumor microenvironment-adaptive nanoplatform(M-mFeP@O_(2)-G),which synergistically enhances the antitumor effect of CDT.Mesoporous Fe_(3)O_(4) nanoparticles are selected as inducers for photothermal and Fenton reactions and as nanocarriers.GOx depletes glucose within tumor cells for starving the cells,while producing H2O2 for subsequent⋅OH generation.Moreover,PFP,which can carry O_(2),relieves hypoxia in tumor cells and provides O_(2) for the cascade reaction.Finally,the nanoparticles are camouflaged with osteosarcoma cell membranes,endowing the nanoparticles with homologous targeting and immune escape abilities.Both in vivo and in vitro evaluations reveal high synergistic therapeutic efficacy of M-mFeP@O_(2)-G,with a desirable tumor-inhibition rate(90.50%),which indicates the great potential of this platform for clinical treating cancer.

关键词： Chemodynamic therapy Tumor microenvironment Cell membranes Homologous targeting perfluoropentane Glucose oxidase

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