Platinum(IV) antitumor complexes and their nano-drug delivery

Platinum-based anticancer drugs dominate the chemotherapy field for several cancers, but problems such as systemic toxicity and acquired resistance for some primary tumors hamper their clinical applications and therapeutic efficacy. Thus, it is necessary to explore alternative strategies to reduce the side effects and improve the pharmacokinetic profiles of platinum complexes. PtIV complexes are highly promising candidates to overcome some problems of clinically approved platinum-drugs. Reduction to toxic PtII species under the reducing intracellular environment is essential for their anticancer activity. Due to this unique mechanism, PtIV drugs can avoid the destruction by the digestive system to a large extent, making them more acceptable to cancer patients through oral treatment. In addition, the structural characteristics of PtIV drugs are different from traditional PtII drugs, such as cisplatin and carboplatin, which allows them to prevent undesired effects and overcome the resistance of cisplatin analogs. Nano-drug delivery systems have become one of the focus areas of new drug research and development because of their good biocompatibility, large drug loading, accurate tumor targeting and other advantages. This overview briefly analyzes mechanisms underlying platinum biological activity and resistance, and then is concerned with the development of PtIV complexes, especially highlighting combination therapy with nanocarriers. The progress that PtIV complexes and nanotechnology have already made will advance platinum-based chemotherapy and promote the translation to clinical applications.