A Rationally Engineered Ru(II) Complex with Long Triplet Lifetime and High Emission Quantum Yield for Imaging-Guided Type I/II Photodynamic Therapy

Abstract Traditional Ru(II)-based photosensitizers (PSs) face a critical dilemma: short triplet metal-to-ligand charge-transfer (3MLCT) lifetimes limit reactive oxygen species (ROS) generation, while long-lived ligand-centered (3LC) states quench 3MLCT emission, hindering desirable imaging-guided PDT. Herein, fused thiophene rings were introduced to finely regulate the photophysical properties of Ru(II)-based PSs. Ru-DTT achieves a precisely engineered excited-state equilibrium between the 3LC state and the 3MLCT state, which simultaneously affords an exceptionally prolonged triplet lifetime (3780 ± 5 ns in H2O) and a considerable luminescence quantum yield (Φem = 0.092 ± 0.005 in H2O). This enables efficient Type I/II ROS generation, facilitating bio-imaging and potent PDT activity under both normoxic and hypoxic conditions in vitro. Furthermore, loading Ru-DTT onto BSA (Ru-DTT@BSA) achieved efficient imaging-guided PDT in vivo by inducing ferroptosis and immunogenic cell death (ICD). Overall, this work highlights that rational excited-state engineering endows Ru(II)-based PSs with appealing theranostic capability.