Rhodamine-Decorated Rhodium(III) Complexes as Theragnostic Agents with Controllable ROS Generation Abilities for Mitochondria-Targeting Type I and Type II Photodynamic Therapy

Though transition metal complexes have been widely developed as potential photosensitizers in photodynamic therapy (PDT), related studies utilizing rhodium(III) complexes are rare due to their less favorable luminescence properties arising from the low-lying d–d excited states and the requirement of high excitation energy. In this work, a series of rhodamine-containing rhodium(III) complexes exhibited moderate rhodamine fluorescence in solutions under ambient conditions and sensitized a considerable amount of singlet oxygen (¹O₂) upon photoexcitation. Additionally, some of the complexes were capable of generating superoxide anion radical (O₂^•–) and hydroxyl radical (HO•) efficiently. Time-resolved transient absorption (TA) spectroscopic results suggested a long-lived dark rhodamine triplet state as a result of the incorporation of the rhodium(III) center, and this lowest-lying state is responsible for the enhanced reactive oxygen species (ROS) photogeneration ability. An energy cascade pathway from rhodamine S₁ to a rhodium-based triplet (T₁’), and subsequently to the lowest rhodamine T₁ was proposed. Interestingly, live-cell studies revealed that the complexes were localized in the mitochondria, and the photogeneration of ROS triggered a loss of mitochondrial membrane potential, leading to cell death. The complexes exhibited promising photocytotoxicity toward MCF-7 cells, via a combination of type I and type II ROS photosensitization mechanisms. This hybrid rhodamine–rhodium(III) system is anticipated to function as innovative theragnostic agents for both imaging and PDT properties.