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As an essential metabolic center of M2 macrophages, the inhibition of protein kinase RNA\u2010like endoplasmic reticulum kinase (PERK) leads to the reduction of M2 macrophages. Nevertheless, the restriction of the blood\u2010brain barrier (BBB) and non\u2010specific cell targeting hinder the application of PERK inhibitors in GBM. Herein, the optimal NP\u2010M\u2010M2pep is developed successfully, which has shown the capacity of BBB penetration and specific targeting of M2 microglia. In addition to inhibiting the polarization of M2 microglia, the administration of iPERK@NP\u2010M\u2010M2pep reprogrammed M2 microglia into M1 ones in vitro via PERK\/HIF\u20101\u03b1\/glycolysis pathway. Efficient brain accumulation of nanoparticles is achieved after tail vein injection, with effective inhibition of GBM progression after one course of treatment. The glioma\u2010associated microglia and macrophages (GAM) with M2 type are induced to M1 and the immunosuppressive TME is remodeled by upregulating immunostimulatory cells and downregulating immunosuppressive cells. In summary, the biomimetic membrane vesicles (BMVs) specifically delivered iPERK to GAMs offer an inspiring strategy to reprogram microglia polarization, re\u2010educate immunosuppressive TME, and inhibit the progression of GBM.<\/jats:p>","DOI":"10.1002\/adhm.202404782","type":"journal-article","created":{"date-parts":[[2025,1,6]],"date-time":"2025-01-06T01:01:20Z","timestamp":1736125280000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Biomimetic Membrane Vesicles Reprogram Microglia Polarization and Remodel the Immunosuppressive Microenvironment of Glioblastoma via PERK\/HIF\u20101\u03b1\/Glycolysis Pathway"],"prefix":"10.1002","volume":"14","author":[{"given":"Yinghan","family":"Guo","sequence":"first","affiliation":[{"name":"Department of Neurosurgery the Second Affiliated Hospital School of Medicine Zhejiang University  Hangzhou Zhejiang 310009 China"},{"name":"Zhejiang Key Laboratory of Research and 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