文献类型：期刊文献

英文题名：Chemotaxis-guided nanoplatform for non-alcoholic steatohepatitis therapy via macrophage reprogramming, hepatoprotection and gut microbiome modulation

作者：Pan, Xier[1];Chen, Xinyi[1];Ma, Ying[1];Zou, Jiafeng[1];Lin, Yiting[1];Zhao, Xinlin[1];Wang, Yanwen[1];Tang, Yun[1];Gao, Feng[1,2,3]

机构：[1]East China Univ Sci & Technol, Shanghai Frontier Sci Ctr Optogenet Tech Cell Meta, Sch Pharm, Shanghai 200237, Peoples R China;[2]East China Univ Sci & Technol, Pharmaceut Engn & Proc Chem Engn Res Ctr, Sch Pharm, Shanghai Key Lab New Drug Design,Minist Educ, Shanghai 200237, Peoples R China;[3]East China Univ Sci & Technol, Shanghai Key Lab Funct Mat Chem, Shanghai 200237, Peoples R China

年份：2026

卷号：326

外文期刊名：BIOMATERIALS

收录：;EI(收录号：20253719167378);WOS:【SCI-EXPANDED(收录号:WOS:001573471500001)】；

基金：This work was financially supported by Development Program of China (grant 2019YFA0904800) ; Joint Funds of the National Natural Science Foundation of China (U23A20530) ; National Natural Science Foundation of China (grant 32150030, 32030065, 32121005, and 92049304) ; Shanghai Frontiers Science Center of Optogenetic Techniques for Cell Metabolism; Natural Science Foundation of Shanghai (grant 22ZR1415500) ; and Research Unit of New Techniques for Live-cell Metabolic Imaging (Chinese Academy of Medical Sciences, grant 2019-I2M-5-013)We thank the exceptional experimental environment of the State Key Laboratory of Bioreactor Engineering (Shanghai) , the Fundamental Research Funds for the Central Universities, and the innovative research team of high-level local universities in Shanghai. We also thank Prof. Yuzheng Zhao (Y.Z., ECUST) for his help and financial support.

语种：英文

外文关键词：M2 macrophage-derived membrane; Nanoplatform; Obeticholic acid; Non-alcoholic steatohepatitis; Macrophage reprogramming; Gut microbiome modulation

摘要：Non-alcoholic steatohepatitis (NASH), characterized by hepatic steatosis, inflammation, and varying degrees of fibrosis, has become a growing global health burden. Obeticholic acid (OCA, a farnesoid X receptor agonist) has shown limited efficacy due to poor solubility, single-target mechanisms, and off-target side effects, notwithstanding the great promise of this agent in NASH clinical trials. Here, we designed M2 macrophage-derived membrane (M2M)-camouflaged poly (lactic-co-glycolic acid) (PLGA) nanoparticles (O@PLGA@M) to achieve targeted OCA delivery to the inflamed liver niche for recovering hepatic homeostasis in NASH. The M2M improved the inflamed liver-targeting of the nanoplatforms via chemotaxis and promoted M1-to-M2 macrophage repolarization, as evidenced by a 2.5-fold increase in CD206 expression and 45 % reduction in CD86 expression in the liver. In a methionine/choline-deficient (MCD) diet-induced murine NASH model, O@PLGA@M exhibited excellent biosafety and multifaceted anti-NASH efficacy, including anti-steatosis, anti-inflammatory, and antifibrotic effects. Mechanistically, O@PLGA@M reprogrammed macrophages by modulating macrophage polarization and inhibiting recruitment of immune cells to reduce the inflammatory cascade. They also exerted hepatoprotection effects by reducing steatosis and hepatocyte damage. Moreover, O@PLGA@M modulated the gut microbiome by redirecting it towards a beneficial state, which further relieved NASH through the gut-liver axis. These findings demonstrated that the biomimetic nanoplatforms could be employed as promising strategies that integrated targeted delivery and multimodal synergistic therapy for NASH management.