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

ABSTRACT

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.