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Cancer cells maintain malignancy by regulating abnormal ATP synthesis and excretion. However, traditional ATP depletion therapy is limited by its short-term efficacy and compensatory drug resistance. This paper introduces a material-driven "transmembrane ATP flux reprogramming" strategy that actively utilizes extracellular ATP efflux to induce tumor-selective biological energy collapse. An octopus-shaped biomimetic nanomachine (named HSA-ABC) equipped with an ATP-responsive module achieves synchronous photodynamic membrane disruption and apoptosis-triggered ATP release. The multi-valent cholesterol anchors the precise positioning of the membrane, initiating a self-amplifying therapeutic cycle: local photodynamic membrane perturbation induces ATP release, which then controls the synchronous release of chlor E6 and doxorubicin, enhancing cell apoptosis and subsequent ATP leakage. This feedback loop induces selective biological energy crisis in malignant cells while preserving normal cells. Unlike traditional metabolic intervention, this method utilizes the intrinsic adaptability of cancer cells to induce self-driven metabolic collapse. This work establishes a new class of metabolic adaptive nanomaterials that can reprogram the dynamics of energy flux, providing a multifunctional platform for precise anti-cancer therapy. This research was published under the title "A Biomimetic Nanomachine Regulates Transmembrane ATP Flux to Trigger Tumor-Specific Bioenergetic Crisis" in Advanced Materials.
References:
DOI: 10.1002/adma.202522412
