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.