Asymmetric A‐DA′D‐A′′ Molecular Configuration Type‐I Photosensitizer with Two Complementary Reactive Oxygen Species for Efficient Imaging and Photodynamic Therapy

Abstract Type‐I photosensitizers (PSs) can efficiently generate reactive oxygen species (ROS) in the hypoxia condition of tumors, which show less oxygen dependence and are considered better candidates for photodynamic therapy (PDT). However, relatively few efficient type‐I organic PSs simultaneously generating two or more type‐I ROS under irradiation are reported. Herein, new alternate donor (D)‐acceptor (A) type molecules containing ladder‐type core (DA′D) fused with an electron‐deficient benzothiadiazole core are reported, which show symmetrical A‐DA′D‐A ( QY1 ) and asymmetrical A‐DA′D‐A′′ ( QY2 ) configurations, respectively. As these ROSs possess complementary properties of strong oxidizing ability (•OH) and long radical lifetime (O 2 •− ), in vitro and in vivo experiments demonstrate that QY1 and QY2 show excellent PDT effects for tumor cells under normoxia or hypoxia, and can achieve remarkable tumor growth inhibition (TGI) rate of 90% for the QY2 . More importantly, the generation of •OH in these PSs is revealed by experiments both in aqueous and in vitro, including the well‐known transformation of O 2 •− and direct electron transition from water to excited triplet PS. It thus provides a comprehensive understanding of the O 2 dependence property of •OH radical and deep insights into the mechanism of type‐I PS.