Organelle-targeted BODIPY-conjugated platinum(IV) anticancer prodrugs for overcoming drug resistance

Platinum-based chemotherapy, despite being a cornerstone of cancer treatment, faces significant challenges due to acquired drug resistance. To address this issue, we have designed three organelle-targeting platinum(IV) prodrugs conjugated with BODIPY fluorophores, enabling spatiotemporal control through green light irradiation. These BODIPY-Pt(IV) conjugates exhibit excellent stability in PBS buffer, demonstrating resilience under physiological conditions. Upon light exposure, these prodrugs undergo rapid activation, releasing axial ligands and generating cytotoxic platinum(II) species at specific cellular locations. In vitro studies across various cancer cell lines, including those resistant to conventional platinum therapies, show high efficacy of these prodrugs, attributed to their organelle-targeted delivery and fast photoactivation. Furthermore, the intrinsic fluorescence of these Pt(IV) prodrugs enables real-time tracking of their cellular distribution, providing valuable insights into their mechanism of action. Overall, our research presents a novel strategy that combines photoactivation of Pt(IV) prodrugs with organelle-specific targeting to overcome platinum drug resistance, enhancing the therapeutic efficacy of platinum-based prodrugs and offering a promising avenue for precision cancer therapy.