H 2 S-Activable BiFeO 3– x Nanocatalysts for Ferroptosis-Driven Cancer Immunotherapy

Controlling ferroptosis through material redox dynamics represents a frontier in the field of catalytic nanomedicine. Here, we introduce nonstoichiometric bismuth ferrite (BiFeO 3– x ) as an H 2 S-activable semiconductor that couples oxygen-vacancy-enabled charge modulation with endogenous sulfur chemistry to achieve spatiotemporally controlled immunogenic ferroptosis. Upon exposure to tumor-enriched gasotransmitter H 2 S, BiFeO 3– x undergoes a transformation into Bi 2 S 3 while releasing Fe 2+ ions to trigger Fenton-like lipid peroxidation. The material’s mixed-valence Fe redox pair amplifies reactive oxygen species generation under 808 nm excitation, coupling photothermal energy dissipation with catalytic ferroptotic stress. Biologically, this multiresponse process initiates mitochondrial collapse, glutathione peroxidase 4 depletion, and lipid peroxide accumulation, driving apoptosis–ferroptosis cascades. In vivo, photoacoustic-guided therapy and mass cytometry profiling reveal profound immune remodeling, such as dendritic cell maturation, CD8 + T cell infiltration, and M1 macrophage polarization, implying the conversion of “cold” colorectal tumors into immunogenic tumor microenvironments. This work establishes a defect-chemistry-oriented design framework for engineering redox-programmable nano semiconductors that translate lattice instability into biological selectivity, bridging ferroelectric materials science and immune oncology.