抗肿瘤铂(Ⅳ)配合物靶向给药系统研究进展

Research Progress of Antitumor Platinum (Ⅳ) Complex Targeted Drug Delivery System

经典的铂(Ⅱ)抗肿瘤药物是临床上针对多种癌症广泛使用的化疗药物.但是,严重的全身毒性和耐药性已成为限制其应用和有效性的主要障碍.由于二价顺铂类似物在体内容易被破坏,因此其生物利用度低,对肿瘤组织没有选择性.而铂(Ⅳ)前药是有潜力的治疗癌症的化合物,它们具有很大的优势.例如,在体内生理环境中具有更高的稳定性.水溶性以及与顺铂无交叉耐药性,使得其可能成为下一代铂类抗肿瘤药.此外,由于铂(Ⅳ)药物可以口服,打破了目前只能注射铂(Ⅱ)药物的现状,这对于癌症患者来说更容易接受.铂(Ⅳ)配合物与肿瘤靶向基团的结合改善了诸如血液不稳定、与血浆蛋白不可逆结合、肾脏快速清除以及正常组织中非特异性分布等局限性.因此,铂配合物和肿瘤靶向基团的结合已成为新的铂药物研究与开发中的热门领域.抗肿瘤铂(Ⅳ)配合物靶向给药系统的构建大致可以分为两类:主动靶向和被动靶向.论文总结了近年来关于铂(Ⅳ)配合物靶向给药系统的构建,为提高治疗效果和减轻铂抗肿瘤药的副作用提供了参考方向.

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 not selective to tumor tissues.The platinum(Ⅳ)prodrugs are attractive compounds for cancer treatment because they have great advantages,like higher stability in physiological environment in vivo,aqueous solubility and no cross-resistance with cisplatin,which may become the next generation of platinum anticancer drugs.In addition,platinum(Ⅳ)drugs can be taken orally,which has broken the current situation that platinum(Ⅱ)drugs can only be given by injection,and is more acceptable for cancer patients.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.The platinum(Ⅳ)complex targeted drug delivery systems can be roughly divided into two categories:active and passive targeted strategies.This review summarizes various targeting and delivery strategies for platinum(Ⅳ)complexes in recent years,and provides a reference direction for improving the therapeutic effect and reducing the side effects of platinum antitumor drugs.