Development of Mitochondria-Targeting BODIPY-NHC-Silver Complex for Synergistic Chemo-Photodynamic Therapy in Red Light

Abstract Treatment of cancer is often hindered by drug resistance and severe side effects associated with conventional chemotherapy. To address these limitations, multimodal therapeutic strategies, such as chemo-photodynamic therapy combining chemotherapy and photodynamic therapy, have emerged as a promising alternative. In this study, we report the design, synthesis, and evaluation of BODIPY–N-heterocyclic carbene (NHC)–silver complexes as chemophototheranostic agents for synergistic cancer treatment. A series of four BODIPY–NHC–silver complexes were synthesized and fully characterized using different spectroscopic techniques. These complexes integrate the imaging capability of BODIPY dyes with the chemotherapeutic potential of silver, while also acting as efficient photosensitizers for the generation of reactive oxygen species (ROS) upon light irradiation. Biological investigations revealed significant anticancer activity under dark conditions, confirming the chemotherapeutic activity of the silver complexes. Among the four BODIPY–NHC–silver complexes, di-iodo-di-styryl-BODIPY-NHC-silver complex 15 showed enhanced cytotoxicity to cancer cells upon photoactivation, confirming synergistic chemo-photodynamic therapeutic effects. Mechanistic studies indicated mitochondrial localization and ROS-mediated mitochondrial network disruption due to the chemo-photodynamic therapeutic effect successfully activating the apoptotic pathway, leading to efficient cancer cell death. Overall, this work highlights the potential of BODIPY–NHC–silver complexes as synthetically accessible and effective platforms for multimodal cancer therapy.