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Selective disruption of mitochondrial metabolism in GBM is challenging because ETC function is also essential for normal brain cells, and many therapeutic agents show limited BBB penetration or reduced activity under oxygen\u2010limited conditions. Here, we report Ni\/LDH@M, an ultrasound\u2010responsive biomimetic Schottky nanoplatform assembled from nickel nanosheets and layered double hydroxide (LDH) nanosheets and cloaked with GL261 glioma cell membranes to enable homotypic recognition and accumulation in orthotopic glioma. Upon ultrasound irradiation, Ni\/LDH@M drives carbon monoxide (CO) generation through interfacial electron modulation, and the generated CO inhibits mitochondrial cytochrome\n                    <jats:italic>c<\/jats:italic>\n                    oxidase, disrupts ETC electron transfer, and induces mitochondria\u2010dependent apoptosis and immunogenic cell death (ICD). In mice bearing orthotopic GL261 gliomas, ultrasound\u2010activated Ni\/LDH@M suppressed tumor progression and prolonged survival, showing that controlled CO generation can reprogram tumor\u2010cell mitochondrial metabolism for GBM therapy.\n                  <\/jats:p>","DOI":"10.1002\/adma.74384","type":"journal-article","created":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T12:33:32Z","timestamp":1786365212000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Ultrasound\u2010Driven Interfacial Electron Modulation Reprograms Mitochondrial Metabolism for Glioblastoma Therapy"],"prefix":"10.1002","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-7494-4117","authenticated-orcid":false,"given":"Wen","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Neurosurgery The First Affiliated Hospital of USTC Division of Life Sciences and Medicine University of Science and Technology 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Anhui China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-4202-574X","authenticated-orcid":false,"given":"Weiyong","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Ultrasound The First Affiliated Hospital of USTC Division of Life Sciences and Medicine University of Science and Technology of China  Hefei Anhui China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuan","family":"Nie","sequence":"additional","affiliation":[{"name":"Department of Pharmacy The First Affiliated Hospital of USTC Division of Life Sciences and Medicine University of Science and Technology of China Hefei Anhui China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0319-4165","authenticated-orcid":false,"given":"Yezi","family":"You","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Precision and Intelligent Chemistry University of Science and 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