Innovative Photosensitizers and Combination Therapies for PDT-Enhanced Antitumor Immunity

Photodynamic therapy (PDT) is a highly targeted and minimally invasive cancer treatment that utilizes light-activated photosensitizers (PSs) to generate reactive oxygen species (ROS) for localized tumor destruction. In addition to its direct cytotoxic effects, PDT can induce immunogenic cell death (ICD), stimulating systemic antitumor immunity. This paper examines recent advancements in PS design aimed at enhancing selectivity, ROS generation, and biocompatibility through molecular modifications, activatable PSs, and nanotechnology-based delivery systems. It also evaluates strategies to enhance PDT-induced immune responses, including combination therapies with cytokines, immune checkpoint inhibitors, and tumor-associated antigen vaccines. Furthermore, approaches to overcoming tumor hypoxia, modulating the tumor microenvironment, and integrating photothermal and photodynamic modalities are analyzed. By assessing the advantages and limitations of these strategies, this study provides insights into optimizing PDT for improved cancer treatment outcomes.