Shewanella oneidensis Metabolically Engineered with Prussian Blue for Synergistic Tumor Microenvironment Remodeling and Photodynamic Breast Tumor Elimination.

Microorganism-based tumor therapy has attracted increasing interest due to the intrinsic tumor tropism and metabolic plasticity of certain bacterial species. However, their therapeutic efficacy is often hindered by insufficient metabolic activity within the tumor microenvironment and safety concerns associated with systemic administration. Here, we develop a biohybrid system, termed Ce6@PB@MR-1, to enhance the intrinsic tumor-targeting behavior of chlorin e6 (Ce6) and lactate-metabolizing capability of Shewanella oneidensis MR-1 (MR-1) through engineered material-microbe coupling. In this system, Prussian blue (PB) is metabolically precipitated onto the MR-1 surface during anaerobic respiration, forming an electron-mediating interface in which PB functions as an efficient exogenous electron acceptor to strengthen respiratory electron flux and accelerate the lactate metabolism of MR-1. The PB coating simultaneously attenuates bacterial immunogenicity, enabling the improved in vivo persistence and safety of MR-1. Furthermore, bioconjugated Ce6 enables 660 nm-triggered photodynamic therapy to induce immunogenic cell death and activate antitumor immune responses. In vivo, the biohybrid system achieves durable tumor eradication accompanied by a marked remodeling of the tumor microenvironment. This work establishes a metabolically assisted material-microbe hybridization framework that expands microbial functionality and offers a versatile strategy for developing safe and effective microbe-based cancer therapies.