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However, in vivo hitchhiking efficiency of NEs is severely limited by spontaneous formation of a nonspecific protein corona. Here, we present pathogen\u2010mimetic liposomes (PM\u2010Lipo) that enable efficient and precise NEs hitchhiking by programming the in vivo protein corona. PM\u2010Lipo is rationally engineered to preferentially enrich complement 3b (C3b) and inactivated C3b (iC3b), thereby recapitulating endogenous complement opsonization and promoting complement receptor 3 (CR3)\u2010mediated recognition by activated NEs. This effect arises from the synergistic integration of two functional lipids that activate distinct complement pathways, triggering a proteolytic cascade with positive feedback to amplify C3b\/iC3b deposition. Our results demonstrate that PM\u2010Lipo achieved &gt;85% targeting efficiency toward activated NEs, enabling hitchhiking\u2010mediated transport across the BBB, with 8.94% of the administered PM\u2010Lipo successfully penetrating the brain, leading to marked tumor suppression and more than a twofold extension in median survival. Our research establishes a protein corona programming strategy to harness endogenous immune cells for targeted drug delivery, offering a broadly applicable paradigm for precision nanomedicine in CNS malignancies.<\/jats:p>","DOI":"10.1002\/adma.74780","type":"journal-article","created":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T14:07:27Z","timestamp":1787580447000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Pathogen\u2010Mimetic Liposomes Customizing Protein Corona for Precision Glioblastoma Therapy"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-9643-0517","authenticated-orcid":false,"given":"Xi","family":"Chen","sequence":"first","affiliation":[{"name":"School of Medical Imaging Division of Medical Technology Tianjin Key Laboratory of Functional Imaging Tianjin Medical University  Tianjin China"},{"name":"State Key Laboratory of Medicinal Chemical Biology College of Chemistry Key Laboratory of Functional Polymer Materials (Ministry of Education) Nankai University Tianjin China"},{"name":"State Key Laboratory of Advanced Medical Materials and Devices Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine Tianjin Institutes of Health Science Institute of Radiation Medicine Chinese Academy of Medical Sciences &amp; Peking Union Medical College Tianjin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Medical Imaging Division of Medical Technology Tianjin Key Laboratory of Functional Imaging Tianjin Medical University  Tianjin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyi","family":"Cai","sequence":"additional","affiliation":[{"name":"School of Medical Imaging Division of Medical Technology Tianjin Key Laboratory of Functional Imaging Tianjin Medical University  Tianjin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingyu","family":"Zhao","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Advanced Medical Materials and Devices Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine Tianjin Institutes of Health Science Institute of Radiation Medicine Chinese Academy of Medical Sciences &amp; Peking Union Medical College Tianjin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong","family":"Ke","sequence":"additional","affiliation":[{"name":"School of Medical Imaging Division of Medical Technology Tianjin Key Laboratory of Functional Imaging Tianjin Medical University  Tianjin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuangxiu","family":"Li","sequence":"additional","affiliation":[{"name":"School of Medical Imaging Division of Medical Technology Tianjin Key Laboratory of Functional Imaging Tianjin Medical University  Tianjin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Medical Imaging Division of Medical Technology Tianjin Key Laboratory of Functional Imaging Tianjin Medical University  Tianjin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9029-8805","authenticated-orcid":false,"given":"Fan","family":"Huang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Advanced Medical Materials and Devices Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine Tianjin Institutes of Health Science Institute of Radiation Medicine Chinese Academy of Medical Sciences &amp; Peking Union Medical College Tianjin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5752-5180","authenticated-orcid":false,"given":"Yang","family":"Liu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Medicinal Chemical Biology College of Chemistry Key Laboratory of Functional Polymer Materials (Ministry of Education) Nankai University Tianjin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6136-9969","authenticated-orcid":false,"given":"Shao\u2010Kai","family":"Sun","sequence":"additional","affiliation":[{"name":"School of Medical Imaging Division of Medical Technology Tianjin Key Laboratory of Functional Imaging Tianjin Medical University  Tianjin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-0659-0125","authenticated-orcid":false,"given":"Zhanzhan","family":"Zhang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Medicinal Chemical Biology College of Chemistry Key Laboratory of Functional Polymer Materials (Ministry of Education) Nankai University Tianjin China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,24]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"crossref","first-page":"v95","DOI":"10.1093\/neuonc\/noac202","article-title":"CBTRUS Statistical Report: Primary Brain and Other Central Nervous System Tumors Diagnosed in The United States in 2015\u20132019","volume":"24","author":"Ostrom Q. 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