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用于癌症治疗的刺激激活型金属前药的最新进展。

Recent progress in stimuli-activable metallo-prodrugs for cancer therapy.

作者信息

Liang Jinzhe, Wei Fangmian, Chao Hui

机构信息

MOE Key Laboratory of Bioinorganic and Synthetic Chemistry Guangdong Basic Research Center of Excellence for Functional Molecular Engineering School of Chemistry Sun Yat-Sen University Guangzhou China.

State Key Laboratory for the Chemistry and Molecular Engineering of Medicinal Resources MOE Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources Collaborative Innovation Center for Guangxi Ethnic Medicine School of Chemistry and Pharmaceutical Sciences Guangxi Normal University Guilin China.

出版信息

Smart Mol. 2024 Aug 29;2(3):e20240030. doi: 10.1002/smo.20240030. eCollection 2024 Sep.

DOI:10.1002/smo.20240030
PMID:40625908
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12118304/
Abstract

The clinical approval of platinum-based drugs has prompted the development of novel metallo-complexes during the last several decades, while severe problems, especially for poor water solubility, drug resistance and toxicity in patients, greatly hindered the clinical trials and curative efficacy. To address these issues, the concept of metallo-prodrugs has been proposed for oncology. Some stimuli-activable metallo-prodrugs provide new insights for designing and preparing site-specific prodrugs with maximized therapeutic efficacy and negligible unfavorable by-effects. In this review, recent progress in stimuli-activable metallo-prodrugs in the past 20 years has been overviewed, where endogenous and exogenous stimuli have been involved. Typical examples of smart stimuli-activable metallo-prodrugs are discussed regarding to their molecular structure, activation mechanism, and promising biomedical applications. In the end, challenges and future perspectives in metallo-prodrugs have been discussed.

摘要

在过去几十年中，铂类药物的临床获批推动了新型金属配合物的研发，然而严重的问题，尤其是水溶性差、耐药性以及患者毒性，极大地阻碍了临床试验和治疗效果。为解决这些问题，金属前药的概念已被引入肿瘤学领域。一些可刺激激活的金属前药为设计和制备具有最大治疗效果且副作用可忽略不计的位点特异性前药提供了新的思路。在本综述中，概述了过去20年中可刺激激活的金属前药的最新进展，其中涉及内源性和外源性刺激。讨论了智能刺激激活金属前药的典型例子，包括它们的分子结构、激活机制以及有前景的生物医学应用。最后，讨论了金属前药面临的挑战和未来展望。

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