College of Chemistry and Molecular Engineering , Nanjing Tech University , Nanjing 211816 , P. R. China.
State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences , Nanjing University , Nanjing 210023 , P. R. China.
Chem Rev. 2019 Jan 23;119(2):1138-1192. doi: 10.1021/acs.chemrev.8b00209. Epub 2018 Oct 9.
The success of platinum-based anticancer agents has motivated the exploration of novel metal-based drugs for several decades, whereas problems such as drug-resistance and systemic toxicity hampered their clinical applications and efficacy. Stimuli-responsiveness of some metal complexes offers a good opportunity for designing site-specific prodrugs to maximize the therapeutic efficacy and minimize the side effect of metallodrugs. This review presents a comprehensive and up-to-date overview on the therapeutic stimuli-responsive metallodrugs that have appeared in the past two decades, where stimuli such as redox, pH, enzyme, light, temperature, and so forth were involved. The compounds are classified into three major categories based on the nature of stimuli, that is, endo-stimuli-responsive metallodrugs, exo-stimuli-responsive metallodrugs, and dual-stimuli-responsive metallodrugs. Representative examples of each type are discussed in terms of structure, response mechanism, and potential medical applications. In the end, future opportunities and challenges in this field are tentatively proposed. With diverse metal complexes being introduced, the foci of this review are pointed to platinum and ruthenium complexes.
几十年来，基于铂的抗癌药物的成功激发了人们对新型金属药物的探索，然而，耐药性和全身毒性等问题阻碍了它们的临床应用和疗效。一些金属配合物的刺激响应性为设计针对特定部位的前药提供了很好的机会，以最大限度地提高治疗效果并最小化金属药物的副作用。本综述全面概述了过去二十年中出现的治疗性刺激响应型金属药物，其中涉及到氧化还原、pH 值、酶、光、温度等刺激。根据刺激的性质，这些化合物分为三类，即内刺激响应型金属药物、外刺激响应型金属药物和双重刺激响应型金属药物。每种类型的代表性实例都根据结构、响应机制和潜在的医学应用进行了讨论。最后，本文还初步提出了该领域的未来机遇和挑战。随着多种金属配合物的引入，本综述的重点是铂和钌配合物。
