Electrogenic HfO2/TiO2 Living Biointerface Dismantles Metabolic Radioresistance for Amplified Radio-Immunotherapy

Radiotherapy (RT) efficacy in aggressive solid tumors is hindered by lactate-driven metabolic radioresistance and an immunosuppressive microenvironment. Here, we engineer a living biointerface (SHT) via in situ biomineralization of HfO 2 /TiO 2 onto an electrogenic Shewanella oneidensis chassis to address this multifaceted challenge. This structural integration bridges the bacterial metabolism with interfacial radiocatalysis. The TiO 2 shell acts as an efficient electron acceptor to accelerate bacterial extracellular electron transfer, driving rapid intratumoral lactate depletion, while the high-Z HfO 2 core enhances the X-ray energy deposition. Under irradiation, this synergistic biointerface initiates an oxidative burst and irreversible DNA damage, dismantling the lactate-associated antioxidant defense. In radioresistant triple-negative breast cancer models, this localized physicochemical disruption translates into tumor suppression, accompanied by immunogenic cell death and cGAS-STING pathway activation, reprogramming the immunosuppressive niche. Furthermore, the SHT platform demonstrates systemic biocompatibility, alongside RT-gated self-limiting clearance. Collectively, this work establishes a bioelectrogenic material platform that integrates metabolic barrier dismantling, radiocatalytic sensitization, and immune remodeling for refractory cancer therapy.