Ir(III)-Based Photosensitizer-Loaded M1 Macrophage Exosomes for Synergistic Photodynamic Therapy

The synthesis of organic photosensitizers with effective reactive oxygen species (ROS) generation remains one of the urgent needs for cancer therapy. In this study, a simple strategy is developed to endow the intrinsic non-photosensitizer fluorophores with profound ROS-generating ability upon light irradiation. This strategy is featured by introducing donor-acceptor (D-A) structured fluorophores as auxiliary ligands into the Ir(III) metal complex, which provides the Ir(III) metal center-based triplet state (T1) as an energy level springboard to efficiently enhance the energy transition to the D-A ligand-based triplet state (T1'). The energy level difference between T1 and T1' can be regulated through altering the cyclometalated ligands of Ir(III), facilitating the energy transfer from T1 to T1' for augmented ROS generation. To improve the pharmacological properties of the obtained D-A coordinated Ir(III) complex, it is incorporated with the exosomes extracted from M1 phenotype macrophages (M1-Exos). The generated nanocomplexes are able to trigger synergistic photodynamic therapy, facilitating the reprogramming of tumor-associated macrophages and eradicating the tumors in mice. This study provides a general strategy to transform non-photosensitizer fluorophores into effective photosensitizers for biomedical applications. In this work, a universal strategy is provided for transforming non-photosensitizer D-A fluorophores with ultra-poor ROS generation into effective photosensitizers and demonstrate their therapeutic potency using M1 macrophage exosomes as the delivery vesicle for photodynamic therapy. image