文献类型：期刊文献

英文题名：Nano Proton Scavengers Modulate Endosomal pH to Inhibit Microglial Activation and Enhance Stroke Recovery

作者：Wang, Xuanlin[1,2];Shi, Yujing[1,2];Gao, Zehua[1,2];Wang, Jing[1,2];Liu, Changsheng[2,3]

机构：[1]East China Univ Sci & Technol, State Key Lab Bioreactor Engn, Shanghai, Peoples R China;[2]East China Univ Sci & Technol, Sch Mat Sci & Engn, Engn Res Ctr Biomed Mat, Minist Educ, Shanghai, Peoples R China;[3]East China Univ Sci & Technol, Frontiers Sci Ctr Materiobiol & Dynam Chem, Shanghai, Peoples R China

年份：2026

外文期刊名：ADVANCED SCIENCE

收录：;Scopus(收录号：2-s2.0-105047910146);WOS:【SCI-EXPANDED(收录号:WOS:001854791700001)】；

基金：This work was supported by the Key Program of the National Natural Science Foundation of China (No. 32230059), the Basic Science Center Program of the National Natural Science Foundation of China (No. T2288102), the National Natural Science Foundation of China (No. 32471406), the Foundation of Frontiers Science Center for Materiobiology and Dynamic Chemistry (No. JKVD1211002), and the Shandong Province Key Research and Development Project (No. 2023CXPT103).

语种：英文

外文关键词：endosomes; inflammation; ischemic stroke; microglia; toll-like receptors

摘要：Endosomes play a crucial role in immune regulation, yet their effect on microglial behavior in ischemic stroke is not well-documented. While drug-loaded nanoparticles can modulate microglial inflammation, their intrinsic biological effects on microglial activation are underexplored. We demonstrate that inhibiting endosomal acidification reduces pro-inflammatory microglial polarization, limits pathological engulfment of neurons, and reduces neuronal apoptosis. To achieve the same effects in vivo, building on a validated dual-site buffering mechanism of sulfonated chitosan, we develop sulfonated Nano Proton Scavengers (sNPS) as a materials-based strategy to modulate endo/lysosomal pH. After cerebral ischemia, sNPS showed greater fluorescence-associated enrichment in the ipsilateral than in the contralateral hemisphere and was associated with brain-resident and infiltrating immune-cell populations. In the injured brain, sNPS alleviated endo/lysosomal acid stress, suppressed TLR3/4-linked inflammatory signaling, and normalized inflammation-driven endo/lysosomal remodeling and proton-loading machinery, thereby restraining maladaptive microglial activation. This immunomodulation was accompanied by improved neural structural preservation and post-stroke survival and functional outcomes. These findings identify endosomal pH homeostasis as a tractable intracellular cue for material-driven immunoregulation and suggest that sNPS offers a complementary therapeutic direction for ischemic stroke.