Targeting drug delivery system for platinum(Ⅳ)-Based antitumor complexes

Classical platinum(II) anticancer agents are widely-used chemotherapeutic drugs in the clinic against a range of cancers. However, severe systemic toxicity and drug resistance have become the main obstacles which limit their application and effectiveness. Because divalent cisplatin analogues are easily destroyed in vivo, their bioavailability is low and no selective to tumor tissues. The platinum(IV) prodrugs are attractive compounds for cancer treatment because they have great advantages, e.g., higher stability in biological media, aqueous solubility and no cross-resistance with cisplatin, which may become the next generation of platinum anticancer drugs. In addition, platinum(IV) drugs could be taken orally, which could be more acceptable to cancer patients, breaking the current situation that platinum(II) drugs can only be given by injection. The coupling of platinum(IV) complexes with tumor targeting groups avoids the disadvantages such as instability in blood, irreversible binding to plasma proteins, rapid renal clearance, and non-specific distribution in normal tissues. Because of the above advantages, the combination of platinum complexes and tumor targeting groups has become the hottest field in the research and development of new platinum drugs. These approaches can be roughly categorized into two groups: active and passive targeted strategies. This review concentrates on various targeting and delivery strategies for platinum(IV) complexes to improve the efficacy and reduce the side effects of platinum-based anticancer drugs. We have made a summary of the related articles on platinum(IV) targeted delivery in recent years. We believe the results of the studies described in this review will provide new ideas and strategies for the development of platinum drugs. • Platinum(IV) emerges as promising candidate for overcoming the shortcomings of platinum(II). • Various DTD systems for platinum(IV) is a hotspot of platinum anticancer chemotherapeutic drugs. • This review provides new ideas and strategies for the development of platinum drugs.