Bioimplantable Bifunctional Zinc/Magnesium–Oxygen Battery for Synergistic Gas Therapy and Hypoxia‐Activated Chemotherapy

Abstract Hydrogen (H 2 ) therapy has emerged as a promising antitumour strategy due to its selective cytotoxicity and biosafety, however, its clinical translation has been hindered by the inability to sustain H 2 release within tumours. Concurrently, hypoxia‐activated prodrugs (HAPs) rely on tumour‐specific oxygen‐depleted microenvironments for activation, nevertheless, their therapeutic efficacy is often limited by insufficient hypoxia. To address these limitations, an implantable bifunctional zinc/magnesium–oxygen (Zn/Mg–O 2 ) battery is developed, which synergistically integrates sustained H 2 generation with oxygen (O 2 ) depletion. Redox reactions are leveraged by the battery to enable continuous intratumoural H 2 release, thereby inducing mitochondrial dysfunction and impairing energy metabolism in cancer cells. Simultaneously, a profoundly hypoxic niche is established through the battery's O 2 consumption, thereby potentiating the tumour‐selective activation of HAPs. This dual‐action mechanism facilitates a combined therapeutic approach: H 2 ‐mediated metabolic disruption and hypoxia‐augmented chemotherapy. The system's robust antitumour performance is validated through in vivo studies, with a tumour inhibition rate exceeding 99% and no observable systemic toxicity. A paradigm‐shifting cancer therapy platform overcomes gas delivery and prodrug activation barriers, offering a translatable strategy for safe, effective combination treatment.