BODI-Pt, a Green-Light-Activatable and Carboplatin-Based Platinum(IV) Anticancer Prodrug with Enhanced Activation and Cytotoxicity

Platinum drugs are widely used in clinics to treat various types of cancer. However, a number of severe side effects induced by the nonspecific binding of platinum drugs to normal tissues limit their clinical use. The conversion of platinum­(II) drugs into more inert platinum­(IV) derivatives is a promising strategy to solve this problem. Some platinum­(IV) prodrugs, such as carboplatin-based tetracarboxylatoplatinum­(IV) prodrugs, are not easily reduced to active platinum­(II) species, leading to low cytotoxicity in vitro. In this study, we report the design and synthesis of a carboplatin-based platinum­(IV) prodrug functionalized with a boron dipyrromethene (bodipy) ligand at the axial position, and the ligand acts as a photoabsorber to photoactivate the platinum­(IV) prodrug. This compound, designated as BODI-Pt, is highly stable in the dark but quickly activated under irradiation to release carboplatin and the axial ligands. A cytotoxic study reveals that BODI-Pt is effective under irradiation, with cytotoxicity 11 times higher than that in the dark and 39 times higher than that of carboplatin in MCF-7 cells. Moreover, BODI-Pt has been proven to kill cancer cells by binding to the genomic DNA, arresting the cell cycle at the G₂/M phase, inducing oncosis, and generating ROS upon irradiation. In summary, we report a green-light-activatable and carboplatin-based Pt­(IV) prodrug with improved cytotoxicity against cancer cells, and our strategy can be used as a promising way to effectively activate carboplatin-based platinum­(IV) prodrugs.