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

Abstract

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 HfO2/TiO2 onto an electrogenic Shewanella oneidensis chassis to address this multifaceted challenge. This structural integration bridges the bacterial metabolism with interfacial radiocatalysis. The TiO2 shell acts as an efficient electron acceptor to accelerate bacterial extracellular electron transfer, driving rapid intratumoral lactate depletion, while the high-Z HfO2 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.