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

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.