Rational Design of Type‐I Photodynamic Agents

Type-I photodynamic agents can not only produce cytotoxic reactive oxygen species, but also directly damage biomolecules through electron/hydrogen transfer process, exhibiting reduced dependence on oxygen concentration in photodynamic therapy (PDT). The rational design of Type-I photodynamic agents has attracted increasing attention. This minireview provides a comprehensive overview of Type-I PDT and its advantages in treating hypoxic tumors. It systematically outlines two complementary design strategies: i) thermodynamic modulation through molecular engineering to block the Type-II energy transfer pathway, and ii) kinetic enhancement of electron/hydrogen transfer to favor the Type-I mechanism. Finally, key challenges in Type-I PDT are discussed, and future perspectives are highlighted to facilitate the clinical translation of Type-I photodynamic agents. We hope this review will stimulate further progress in the development of innovative PDT.