Oligopeptide template-guided nanoconfined in situ mineralization of nanotherapeutics boosts self-sufficient immunogenic phototherapy

As a promising cancer treatment modality that has emerged, photodynamic / photothermal therapy can harness antitumor immunity by triggering immunogenic cell death in addition to direct cell ablation. However, the efficacy of this phototherapy is always limited due to the hypoxic tumor microenvironment, and the induccd immune stimulation is insufficient to achieve satisfactory cancer eradication. We herein address the above issues by nanoconfined in situ mineralization of manganese oxide (MnO₂) guided with an oligopeptide as template. The synthetic nanocomposites can be co-assembled efficiently with the photosensitiser through π-π stacking interactions. Crucially, the mineralised MnO₂ composition catalytically decomposes tumor-derived hydrogen peroxide to alleviate the hypoxic microenvironment, thereby improving the efficacy of the photosensitiser in ROS generation. In the murine model of 4 T1 xenograft tumors, the fabricated nanotherapeutics elicited robust antitumor immune responses and boost immunogenic phototherapy toward malignant tumors.