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Overcoming this dual defense established by BBB\u2010TME is a critical challenge in GBM therapy. Here, we present a glucose oxidase (GOD)\u2010powered liposomal nanobot (lipoNbot) to breach the BBB\u2010TME through self\u2010homing navigation guided by the acid and glucose in TME\u2014a mechanism rooted in the regulation of GOD activity, with optimal performance in acidic environments to actively deliver drugs for GBM chemotherapy. The lipoNbot features an asymmetric structure composed of GOD\u2010modified cancer cell membranes and \u03b3\u2010glutamylated lipids, which synergistically enhance BBB\u2010TME penetration through chemotactic diffusiophoresis and \u03b3\u2010glutamyl transferase (GGT)\u2010mediated transcytosis. The proton sponge effect facilitates lysosomal escape for BBB traversal. In vivo investigation indicates that lipoNbots achieve a 4.3\u2010fold increase in delivery efficiency. Such a lipoNbot poses the specific biochemical cues of GBM for self\u2010homing navigation, establishing a proof\u2010of\u2010concept framework utilizing the pathological features for active therapy of central nervous system diseases.<\/jats:p>","DOI":"10.1002\/anie.202512948","type":"journal-article","created":{"date-parts":[[2025,9,15]],"date-time":"2025-09-15T05:39:53Z","timestamp":1757914793000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["A Self\u2010Homing Liposomal Nanobot for Active Therapy of Glioblastoma"],"prefix":"10.1002","volume":"64","author":[{"given":"Yanfang","family":"Cheng","sequence":"first","affiliation":[{"name":"School of Medicine and Health Harbin Institute of Technology  Xidazhi Street 92 Harbin 150001 China"},{"name":"Wenzhou Institute University of Chinese Academy of Sciences  Jinlian Road 1 Wenzhou 325000 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