The Next Generation of Platinum Drugs: Targeted Pt(II) Agents, Nanoparticle Delivery, and Pt(IV) Prodrugs.
The Next Generation of Platinum Drugs: Targeted Pt(II) Agents, Nanoparticle Delivery, and Pt(IV) Prodrugs.
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DOI：
10.1021/acs.chemrev.5b00597
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发表时间：
2016-03-09
期刊：
影响因子：
62.1
通讯作者：
Lippard SJ
中科院分区：
文献类型：
--
作者：
Johnstone TC;Suntharalingam K;Lippard SJ
铂类药物顺铂、卡铂和奥沙利铂在癌症治疗中占主导地位，但新的铂类药物进入临床的速度很慢。然而，最近，基于大量的机制信息，开发非经典铂配合物的活动激增，其作用机制与已批准的药物不同。纳米递送装置的使用也在增长，并且已经探索了许多不同的策略来将铂弹头纳入纳米医学结构中。在这篇综述中，我们讨论了这些努力，以创造下一代铂抗癌药物。引言为读者提供了使用的简要概述，发展，以及批准的铂类药物的作用机制，以提供最近研究蓬勃发展的背景。然后，我们描述了探索具有反几何和单功能配位模式的非经典铂（II）配合物、多核铂（II）化合物、铂（IV）前药、双重治疗剂和光活化铂（IV）配合物的方法。设计用于递送铂（IV）配合物的纳米递送粒子也将被讨论，包括碳纳米管、碳纳米粒子、金纳米粒子、量子点、上转换纳米粒子和聚合物胶束。其他纳米配方，包括超分子自组装结构，蛋白质，肽，金属有机框架和配位聚合物将被描述。最后，综述了铂（II）药物纳米颗粒制剂的重要临床进展。我们预计，这种不同研究成果的综合不仅有助于产生新的药物开发思路和策略，而且也反映了我们对下一代铂类抗癌药物即将到来的乐观态度。
The platinum drugs, cisplatin, carboplatin, and oxaliplatin, prevail in the treatment of cancer,, but new platinum agents have been very slow to enter the clinic. Recently, however, there has been a surge of activity, based on a great deal of mechanistic information, aimed at developing non-classical platinum complexes that operate via mechanisms of action distinct from those of the approved drugs. The use of nanodelivery devices has also grown and many different strategies have been explored to incorporate platinum warheads into nanomedicine constructs. In this review, we discuss these efforts to create the next generation of platinum anticancer drugs. The introduction provides the reader with a brief overview of the use, development, and mechanism of action of the approved platinum drugs to provide the context in which more recent research has flourished. We then describe approaches that explore non-classical platinum(II) complexes with trans geometry and with a monofunctional coordination mode, polynuclear platinum(II) compounds, platinum(IV) prodrugs, dual-treat agents, and photoactivatable platinum(IV) complexes. Nanodelivery particles designed to deliver platinum(IV) complexes will also be discussed, including carbon nanotubes, carbon nanoparticles, gold nanoparticles, quantum dots, upconversion nanoparticles, and polymeric micelles. Additional nanoformulations including supramolecular self-assembled structures, proteins, peptides, metal-organic frameworks, and coordination polymers will then be described. Finally, the significant clinical progress made by nanoparticle formulations of platinum(II) agents will be reviewed. We anticipate that such a synthesis of disparate research efforts will not only help to generate new drug development ideas and strategies, but also reflect our optimism that the next generation of platinum cancer drugs is about to arrive.