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Here, we present a materials\u2010driven strategy for \u201ctransmembrane ATP flux reprogramming\u201d that actively exploits extracellular ATP efflux to induce tumor\u2010selective bioenergetic collapse. An octopus\u2010like biomimetic nanomachine (named HSA\u2010ABC) equipped with ATP\u2010responsive modules that enable synchronized photodynamic membrane disruption and apoptosis\u2010triggered ATP release. Multivalent cholesterol anchors guide precise membrane localization, initiating a self\u2010amplifying therapeutic cycle: localized photodynamic membrane perturbation induces ATP release, which in turn gates the synchronized discharge of Chlorin e6 and doxorubicin, amplifying apoptosis and subsequent ATP leakage. This feedforward loop induces a selective bioenergetic crisis in malignant cells while sparing normal cells. In contrast to conventional metabolic interventions, this approach exploits the intrinsic adaptability of cancer cells to provoke self\u2010driven metabolic collapse. This work establishes a new class of metabolically adaptive nanomaterials capable of reprogramming energy flux dynamics, offering a versatile platform for precision anticancer therapy.<\/jats:p>","DOI":"10.1002\/adma.202522412","type":"journal-article","created":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T10:04:01Z","timestamp":1774951441000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A Biomimetic Nanomachine Reprograms Transmembrane ATP Flux to Induce Tumor\u2010Selective Bioenergetic Crisis"],"prefix":"10.1002","volume":"38","author":[{"given":"Feng","family":"Cheng","sequence":"first","affiliation":[{"name":"Chongqing Science and Technology Bureau College of Pharmaceutical Sciences Key Laboratory of Biomedical Analytics (Southwest University) Southwest University Chongqing 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