Immuno-photodynamic Therapy (IPDT): Organic Photosensitizers and Their Application in Cancer Ablation

[Image: see text] Photosensitizer-based photodynamic therapy (PDT) has been considered as a promising modality for fighting diverse types of cancers. PDT directly inhibits local tumors by a minimally invasive strategy, but it seems to be incapable of achieving complete eradication and fails to prevent metastasis and recurrence. Recently, increasing events proved that PDT was associated with immunotherapy by triggering immunogenic cell death (ICD). Upon a specific wavelength of light irradiation, the photosensitizers will turn the surrounding oxygen molecules into cytotoxic reactive oxygen species (ROS) for killing the cancer cells. Simultaneously, the dying tumor cells release tumor-associated antigens, which could improve immunogenicity to activate immune cells. However, the progressively enhanced immunity is typically limited by the intrinsic immunosuppressive tumor microenvironment (TME). To overcome this obstacle, immuno-photodynamic therapy (IPDT) has come to be one of the most beneficial strategies, which takes advantage of PDT to stimulate the immune response and unite immunotherapy for inducing immune-OFF tumors to immune-ON ones, to achieve systemic immune response and prevent cancer recurrence. In this Perspective, we provide a review of recent advances in organic photosensitizer-based IPDT. The general process of immune responses triggered by photosensitizers (PSs) and how to enhance the antitumor immune pathway by modifying the chemical structure or conjugating with a targeting component was discussed. In addition, future perspectives and challenges associated with IPDT strategies are also discussed. We hope this Perspective could inspire more innovative ideas and provide executable strategies for future developments in the war against cancer.