Recent Organic Photosensitizer Designs for Evoking Proinflammatory Regulated Cell Death in Antitumor Immunotherapy

Abstract

In the past decades, immunotherapy has achieved a series of clinical successes in the field of cancer. However, existing therapeutic options usually show a low immune response to solid tumors caused by immunosuppressive "cold" tumor microenvironment (TME). Several types of proinflammatory regulated cell death (RCD), mainly including ferroptosis and pyroptosis, have been studied recently, which can provide proinflammatory signals and immunogenicity necessary for remodeling TME and activating an antitumor immune response. A variety of chemotherapeutic drugs are proven to be effective in the proinflammatory RCD induction of tumor cells, but several adverse effects and intrinsic drug resistance usually occur in the therapeutic process, greatly hindering their further clinical application. The emerging organic photosensitizer (PS)-based materials open new possibilities to effectively activate proinflammatory RCD through precise spatiotemporal regulation of intracellular reactive oxygen species-associated signaling pathways, which can overcome many challenges encountered in current proinflammatory RCD-mediated immunotherapy. In this review, the recent design strategies of PS probes are detailly summarized and their potential advantages for tumor-specific proinflammatory RCD induction are discussed. Moreover, the representative examples in cancer immunotherapy are highlighted and future perspectives in this emerging field are proposed.

Keywords: antitumor immunotherapy; ferroptosis; organic photosensitizers; proinflammatory regulated cell death; pyroptosis.