Advances in Platinum(IV) Functional Axial Ligand Research: A Prospective Perspective

Malignant tumors have become the second leading cause of death after cardiovascular and cerebrovascular diseases, with their incidence and mortality rates remaining persistently high. Since the discovery of cisplatin's potent antitumor effects, platinum-based drugs have become a cornerstone in cancer therapy. However, the development of resistance and toxicity to normal cells following long-term use of platinum-based drugs poses significant challenges for patients. This has spurred researchers to actively explore novel platinum-based anticancer agents. Among these, platinum(IV) compounds offer a promising solution to the aforementioned issues and are gradually emerging as a viable approach in cancer treatment. This study provides an in-depth review of recent advancements in this field, emphasizing the critical need for developing strategies to control intracellular reduction of Pt(IV) prodrugs. Additionally, it explores how the axial ligands of platinum(IV) prodrugs enhance the cancer-targeting properties of platinum(IV) prodrugs and achieve synergistic effects through controlled release via external mechanisms in cancer cells, thereby reducing the toxic side effects of platinum drugs and lowering drug resistance. Furthermore, this review addresses current challenges in the field and offers insights into potential future research directions. Its analysis aims to assist researchers in rationally designing safe and efficient platinum(IV) prodrugs for precision cancer therapy.