Tumor‐Resident Intracellular Bacteria Scavenger Activated In Situ Vaccines for Potent Cancer Photoimmunotherapy

In situ tumor vaccines, which utilize antigens generated during tumor treatment to stimulate a cancer patient's immune system, has become a potential field in cancer immunotherapy. However, due to the immunosuppressive tumor microenvironment (ITME), the generation of tumor antigens is always mild and not sufficient. Tumor-resident intracellular bacteria have been identified as a complete tumor microenvironment component to contribute to creating ITME. Herein, a tumor-resident intracellular bacteria scavenger is designed to induce enhanced antitumor photoimmunotherapy-driven in situ vaccines for treating hypoxic tumors. This scavenger is developed by integrating photosensitizer CyI and antibiotics Doxycycline (Doxy) into thermal-sensitive tumor-derived exosomes fused liposomes (ECDL). In vitro and in vivo results showed that ECDL could homologous target to cancer cells and restrict the respiration of mitochondrial to reduce tumor hypoxia, thus providing continuous oxygen to eliminate both tumor cells and tumor-resident intracellular bacteria, which could induce in situ vaccines for ablating the primary tumor and inhibiting the tumor metastasis and recurrence. Moreover, eliminating tumor-resident intracellular bacteria neutralizes the ITME and triggers the production of bacterial-related neoantigens, which could further strength the immunotherapy. This study provided versatile and effective in situ vaccines that are promising for local, abscopal, and metastatic tumor treatment.