Molecular Dipole Moment Regulation of NIR‐Ir(III) Complex for Boosting Tumor Phototheranostics

Abstract The development of highly efficient near‐infrared (NIR) photosensitizers capable of boosting triplet excitons population represents a critical pursuit in photodynamic therapy. Although iridium‐based photosensitizers have exhibited excellent photocatalytic performance, the in vivo applications are still hindered by the insufficient NIR light harvesting. The design of a single Ir(III) complex that synchronously possesses remarkable absorption intensity in NIR region, potent reactive oxygen species generating ability remains highly desirable yet challenging. In this work, inspired by the optimization strategies in photocatalysis, a mash‐up strategy combining ligand regulation is established with molecular dipole moment manipulation to construct an NIR‐Ir(III) complex, C6‐Ir‐N, for high‐performance tumor therapy. Density functional theory calculations demonstrate that variation in the molecular dipole moment significantly suppresses the intramolecular charge transfer, thereby amplifying ROS production. Eventually, under the NIR light irradiation, fluorescence imaging‐guided photodynamic/photothermal therapy in a 4T1 tumor‐bearing mouse model is accomplished utilizing the optimized C6‐Ir‐N nanoparticles, showing excellent antitumor efficacy outcomes and good biocompatibility.