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In this study, a lipid\u2010polymer nanoparticle is synthesized to execute compartmentalized Cas9 and sgRNA delivery for a permanent vasculature editing strategy by knocking out the signal transducer and activator of transcription 3 (STAT3). The phenylboronic acid branched cationic polymer is designed to condense sgRNA electrostatically (inner compartment) and patch Cas9 coordinatively (outer compartment), followed by liposomal hybridization with angiopep\u20102 decoration for blood\u2013brain barrier (BBB) penetration. The lipid\u2010polymer nanoparticles can reach glioblastoma within 2\u00a0h post intravenous administration, and hypoxia in tumor cells triggers charge\u2010elimination and degradation of the cationic polymer for burst release of Cas9 and sgRNA, accompanied by instant Cas9 RNP assembly, yielding \u224850% STAT3 knockout. The downregulation of downstream vascular endothelial growth factor (VEGF) reprograms vasculature normalization to improve immune infiltration, collaborating with interleukin\u20106 (IL\u20106) and interleukin\u201010 (IL\u201010) reduction to develop anti\u2010glioblastoma responses. Collectively, the combinational assembly for compartmentalized Cas9\/sgRNA delivery provides a potential solution in glioblastoma therapy.<\/jats:p>","DOI":"10.1002\/advs.202309314","type":"journal-article","created":{"date-parts":[[2024,6,23]],"date-time":"2024-06-23T04:23:25Z","timestamp":1719116605000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Lipid\u2010Polymer Nanoparticles Mediate Compartmentalized Delivery of Cas9 and sgRNA for Glioblastoma Vasculature and Immune Reprogramming"],"prefix":"10.1002","volume":"11","author":[{"given":"Huaqing","family":"Zhang","sequence":"first","affiliation":[{"name":"State Key Laboratory of Natural Medicines Department of Pharmaceutics China Pharmaceutical University  Nanjing 210009 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenxin","family":"Jiang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Natural Medicines 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