Microbial-Semiconductor Hybrids Enable Near Infrared-Driven Photosynthetic Hydrogen Production for Tumor-Targeted Immunotherapy.

Photosynthetic hydrogen (H2)-generating microbes represent a highly promising H2 delivery platform for antitumor therapy due to their spontaneous tumor colonization and high catalytic selectivity. However, existing microbes suffer from inadequate near-infrared (NIR) responsiveness and photoelectron injection. Here, we engineer a microbial-semiconductor hybrid by electrostatically assembling copper sulfide-loaded layered double hydroxide (LDH/CuS) nanosheets onto the surface of Rhodopseudomonas palustris (R.P.) for NIR-driven photosynthetic H2 immunotherapy. The LDH/CuS enhances NIR capture and forms a p‒n heterojunction that weakens the electron exclusion barrier, enabling directed pumping of photogenerated electrons into R.P. Under 808 nm irradiation, the LDH/CuS heterojunction boosts photoelectron injection into the hydrogenase system of R.P. by 6.8-fold, achieving highly efficient photosynthetic H2 production. Notably, the R.P.@LDH/CuS actively colonizes hypoxic tumors with a high targeting efficiency of 73.2% and selectively converts tumor-enriched lactic acid (LA) and glycogen into H2 under NIR stimulation. Through the LA depletion and immunogenic cell death induction, the microbial-semiconductor hybrid triggers potent antitumor immune responses, increasing infiltrated CD8+ T cells by over 9-fold and achieving a remarkable tumor inhibition rate of 97.8%. This work presents an NIR-driven biohybrid system with spatially directional electron pumping for efficient photosynthetic H2 generation, advancing a promising paradigm for precision-targeted tumor immunotherapy.