Ruimin Xue, Chaojie Yu, Tao Wang, Yi Yang, Shibo Wang, Yanfang Zhu, Wanning Jin, Tingting Hu, Chaoliang Tan, Ruizheng Liang
ABSTRACT Photosynthetic hydrogen (H 2 )‐generating microbes represent a highly promising H 2 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 H 2 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 H 2 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 H 2 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 H 2 generation, advancing a promising paradigm for precision‐targeted tumor immunotherapy.