An Engineered Bacterial Platform Combining Photothermal Ablation with Immunogenic Cell Death and Microenvironment Remodeling for Synergistic Tumor Therapy.

Cancer poses a significant burden on human health and has emerged as a pressing global public health issue. Conventional cancer therapies are constrained by poor spatial precision in drug delivery, inadequate immunogenic cell death, and persistence of immunosuppressive M2-like tumor-associated macrophages. These limitations perpetuate off-target toxicity, immune evasion, and tumor recurrence. In this study, we engineered an integrated therapeutic platform, HA/IR780@Bac, through leveraging hypoxia-responsive Escherichia coli to co-deliver immunomodulating hyaluronic acid (HA) and the photothermal agent IR780 for synergistic cancer eradication. The system exploited bacterial tropism to achieve tumor-targeted accumulation, and mediated localized photothermal ablation of tumor cells while concurrently triggered robust immunogenic cell death. This immunogenic cell death cascade-initiated cancer immunogenicity and reversed immunosuppression, which was further amplified by HA-driven polarization of tumor-associated macrophages from pro-tumoral M2 to antitumoral M1 phenotype. Therefore, the HA/IR780@Bac system, which combined targeted delivery, photothermal effect, immunogenic cell death activation, and macrophage reprogramming, could establish a robust paradigm for synergistic tumor treatment.