Photothermal probiotics delivery of photodynamic agents for enhanced immunogenic cell death within hypoxia center of solid tumors

Resulting from harsh hypoxic environmental conditions, central cells in the core of solid tumors are usually more aggressive and malignant with a less stable genome. Therefore, therapeutic agents with improved penetration for the activation of immunity in tumor centers exhibit promising potential in immunotherapies. Here, polydopamine-coated Escherichia coli Nissle 1917 (EcN) bearing chlorin e6 (Ce6)-loaded and polyethyleneimine (PEI)-coated hollow manganese dioxide (shorted as EP-ChP) are applied for enhanced immunotherapy in deep tumors. After accumulation in tumor center through hypoxia targeting, manganese dioxide is degradated under the tumor microenvironment with released Ce6 and thus generates reactive oxygen species (ROS) upon 660 nm laser irradiation, which can further lower thermal-resistance of cancer cells via HSP90α downregulation. Owing to that, heating induced by polydopamine upon 808 nm laser irradiation can achieve effective tumor ablation. Phototherapy upon dual laser induces enhanced immunogenic cell death, while bacterial infections in tumor tissues also trigger innate immunity. This bacteria-based approach provides enhanced antitumor immune responses in deep tumors with great potential in the reshaping of immunosuppression tumor microenvironment.