The hypoxia-tolerant iridium (Ⅲ) based photosensitizer induces immunogenic death of melanoma by producing hydroxyl radicals

Traditional photosensitizers produce highly oxygen-dependent type-Ⅱ ROS singlet oxygen to kill tumors, but the anoxic microenvironment of tumors limits the effectiveness of these photosensitizers, so it is necessary to develop hypoxic-tolerant photosensitizers. In this study, compared with the commercial photosensitizer Ce6, the novel iridium (Ⅲ)-based photosensitizer Ir-1 produced type-Ⅰ ROS hydroxyl radicals to kill murine melanoma B16-F10 cells and induce apoptosis, pyroptosis and ferroptosis under hypoxia condition. Furthermore, it induces immunogenic death of B16-F10 cells and thus induces dendritic cell maturation in vitro. Moreover, Ir-1-mediated photodynamic therapy inhibited the growth of murine subcutaneous implanted melanoma and induced the anti-tumor immune response. Therefore, Ir-1 can effectively kill melanoma cells and induce anti-tumor immune response by producing hydroxyl free radicals under hypoxia condition.