Faculty of Life Science and Technology, Kunming University of Science and Technology, Kunming, 650500, China.
Kunming Guiyan Pharmaceutical Co.Ltd, Kunming, Yunnan, 650221, China.
Eur J Med Chem. 2020 May 15;194:112229. doi: 10.1016/j.ejmech.2020.112229. Epub 2020 Mar 20.
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.
经典的铂(II)类抗癌药物是临床上广泛应用于多种癌症的化疗药物。然而，严重的全身毒性和耐药性已成为限制其应用和疗效的主要障碍。由于二价顺铂类似物在体内易被破坏，其生物利用度低，对肿瘤组织无选择性。铂(IV)前药是治疗癌症的有吸引力的化合物，因为它们具有很大的优势，例如，在生物介质中更高的稳定性、水溶性和与顺铂无交叉耐药性，可能成为下一代铂类抗癌药物。此外，铂(IV)药物可以口服，这可能更能被癌症患者接受，打破了铂(II)药物只能注射的现状。铂(IV)配合物与肿瘤靶向基团的偶联可以避免血液不稳定、与血浆蛋白不可逆结合、快速肾清除和正常组织中非特异性分布等缺点。由于上述优点，铂配合物与肿瘤靶向基团的结合已成为新型铂类药物研发中最热门的领域。这些方法大致可以分为两类：主动和被动靶向策略。本文综述了各种用于铂(IV)配合物靶向传递的策略，以提高疗效并降低铂类抗癌药物的副作用。我们对近年来有关铂(IV)靶向传递的相关文章进行了总结。我们相信，本综述中描述的研究结果将为铂类药物的开发提供新的思路和策略。
