Recent Progress of Molecular Design in Organic Type I Photosensitizers

Photodynamic therapy (PDT) represents a high-efficient and non-invasive therapeutic modality for current and future tumor treatments, drawing extensive attention in the fields of antitumor drug and clinical phototherapy. In recent years, the photosensitizer (PS) market and PDT clinical applications have expanded to address various cancers and skin diseases. However, hypoxic environment within tumors poses a substantial challenge to the therapeutic capability of reactive oxygen species-dependent PDT. Consequently, researches have increasingly focus from the type II to type I PDT mechanism, which relies on radical production with less or no oxygen dependence. Despite significant progress in the development of type I PSs, a holistic understanding regarding the design principles for these molecules remains elusive. Specifically, electron transfer-mediated type I PDT are extensively studied in recent years but is insufficiently addressed in existing reviews. This review systematically summarizes recent advancements in the molecular design rationales of organic type I PSs, categorizing them into three key fundamental strategies: modulating PS charge distribution, singlet oxygen forbidden via low triplet excited state, and accelerating PS radical formation via inducing electron transfer. This review aims to offer valuable insights for the future type I PS design and the advancement of anti-hypoxia PDT.