Engineered Bacteria Labeled with Iridium(III) Photosensitizers for Enhanced Photodynamic Immunotherapy of Solid Tumors

Despite metal-based photosensitizers showing great potential in photodynamic therapy for tumor treatment, the application of the photosensitizers is intrinsically limited by their poor cancer-targeting properties. Herein, we reported a metal-based photosensitizer-bacteria hybrid, Ir-HEcN, via covalent labeling of an iridium(III) photosensitizer to the surface of genetically engineered bacteria. Due to its intrinsic self-propelled motility and hypoxia tropism, Ir-HEcN selectively targets and penetrates deeply into tumor tissues. Importantly, Ir-HEcN is capable of inducing pyroptosis and immunogenic cell death of tumor cells under irradiation, thereby remarkably evoking anti-tumor innate and adaptive immune responses in vivo and leading to the regression of solid tumors via combinational photodynamic therapy and immunotherapy. To the best of our knowledge, Ir-HEcN is the first metal complex decorated bacteria for enhanced photodynamic immunotherapy. An iridium (III) photosensitizer-bacteria hybrid (Ir-HEcN) targets the solid tumors and produces reactive oxygen species in situ upon photoirradiation, which induces pyroptosis of tumor cells and spontaneous self-elimination of Ir-HEcN. The resulting debris further evokes innate and adaptive anti-tumor immune responses. Therefore, Ir-HEcN-mediated treatment remarkably eradicates solid tumors via enhanced photodynamic immunotherapy.+image

Automated summary

Ir-HEcN is a metal complex decorated bacteria that targets tumor tissues and induces pyroptosis and immunogenic cell death of tumor cells under irradiation. It evokes anti-tumor immune responses and leads to the regression of solid tumors via enhanced photodynamic immunotherapy.