Engineering Photothermal and H₂S‐Producing Living Nanomedicine by Bacteria‐Enabled Self‐Mineralization

Abstract Bacteria‐initiated cancer therapy has been demonstrated high therapeutic efficacy against cancer. However, the undesired therapeutic efficacy and induced systematic inflammation storm compromise the therapeutic effect and outcome. Herein, a thermally‐activated living nanomedicine composed of reactive biohybrid (designated as Sa@FeS) is rationally designed and engineered for enhancing hydrogen sulfide (H₂S)‐combined chemodynamic oncotherapy by biomineralizing ferrous sulfide nanoparticles (FeS NPs) onto the surface of a Salmonella typhimurium strain (Sa) without reducing bacterial activity. Ascribed to the deep penetration capability of Sa, FeS NPs facilitate photothermally‐enhanced catalytic Fenton reaction of decomposing endogenous H₂O₂ into cytotoxic hydroxyl radicals deep in tumor tissues upon near infrared irradiation. Meanwhile, Sa bacteria maintain sustained H₂S release within tumor for achieving H₂S‐induced intracellular acidosis that favors the generation of reactive oxygen species synergistically. Of note, the thermally‐triggered all‐in‐one strategy effectively inhibits bacterial viability, thus reducing the risk of systematic inflammation storm and ensuring biosafety. Therefore, the engineered nano‐bacteria living system exerts the thermally‐enhanced nanocatalytic and gas therapies to effectively eradicate tumors, providing a distinct paradigm for the combination of synthetic biology and nanomedicine in tumor therapy.