Advances in technical strategies for monitoring the reduction of platinum(iv) complexes

Platinum(iv) prodrugs have emerged as highly promising candidates for next-generation anticancer drugs. The activation of these prodrugs heavily relies on the critical step of chemical reduction of platinum, which determines their ultimate efficacy as potent anticancer agents. Therefore, it is essential to employ effective strategies to monitor the reduction of Pt(iv) complexes and the generation of active Pt(ii) counterparts. These strategies not only unravel the intracellular mechanisms but also facilitate the design of novel Pt(iv) prodrugs for cancer therapy and enable the prediction of their anticancer performance. In this review, we summarize recent advances in strategies used to monitor the reduction profiles of Pt(iv) complexes from an introductory yet comprehensive viewpoint. We first delve into the principles underlying the reduction of Pt(iv) prodrugs to Pt(ii) species, with a focus on the detection foundations that rely on changes in molecular weight, electronic arrangement, and coordination patterns. We subsequently summarize the strategies employed to investigate the reduction progress of Pt(iv) complexes in both aqueous solutions and at the cellular level, while highlighting the scope of applications, advantages, and disadvantages of each method. Finally, we provide a concise summary and a critical assessment of the discussed approaches. We hope this account will empower researchers with a deeper understanding of the strategies for monitoring the activation of Pt(iv) prodrugs and shed light on the underlying mechanism of prodrug activation. © 2024 The Royal Society of Chemistry.