Hypoxia‐tolerant photodynamic therapy: Bridging oxygen limitation and cancer immunity

Tumor hypoxia severely compromises conventional photodynamic therapy (PDT) and immunotherapy (IT) by restricting oxygen‐dependent reactive oxygen species (ROS) generation and upregulating immune inhibition‐related factors. Type‐I photosensitizers (PSs) offer an effective solution for PDT by producing radical species through electron‐transfer pathways under oxygen‐deficient conditions. Additionally, hypoxia‐tolerant PDT‐induced irreversible cell damage causes immunogenic cell death (ICD) that could initiate an immune response. In the hypoxic tumor environment, Type‐I PSs have achieved the simultaneous enhancement of PDT and IT effects. This perspective summarizes recent advances in hypoxia‐tolerant PDT and photoimmunotherapy. We also summarize several methods for enhancing intramolecular charge transfer in Type‐I PSs through structural adjustment, the pathways for inducing immune responses by Type‐I PSs, as well as highly biologically safe phototherapy strategies. Finally, another perspective is proposed for advanced Type‐I PSs with high therapeutic efficacy and low toxicity.