Bacterial Armory: Engineering Dual Photosensitized Bacteria for a Triple‐Modal Therapy on Tumors

Abstract Bacteria‐mediated cancer therapy offers great promise for tumor targeting and immune activation but faces challenges of limited potency and biosafety. Here, a reinforced platform, E@PB, is developed by coating E. coli Nissle 1917 with polydopamine (PDA) and a cationic BODIPY‐based photosensitizer (BOD‐QAS). This dual‐photosensitized system integrates photothermal and photodynamic modalities while maintaining bacterial viability. The PDA coating enhances tumor colonization and immune stimulation through 808 nm laser‐induced hyperthermia, whereas BOD‐QAS enables 660 nm‐triggered reactive oxygen species generation for tumor cell apoptosis and bacterial growth regulation. The photosensitizer shell also provides real‐time fluorescence imaging, improving therapeutic precision. A two‐stage “green‐to‐red light” strategy allows spatiotemporal control of bacterial activity, maximizing both efficacy and safety. E@PB accumulates rapidly at tumor sites within 8 h and remains for extended periods, enabling sustained therapeutic action. In vivo evaluation demonstrates an 89.8% reduction in tumor volume, highlighting the potential of this triple‐modal system to synergize phototherapy and immune activation in bacteria‐based cancer treatment.