Yang Jinrong, Chen Yu, Chao Hui
MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, State Key Laboratory of Anti-Infective Drug Discovery and Development, Guangdong Basic Research Center of Excellence for Functional Molecular Engineering, School of Chemistry, Sun Yat-Sen University Guangzhou 510006 P. R. China
MOE Key Laboratory of Theoretical Organic Chemistry and Functional Molecule, School of Chemistry and Chemical Engineering, Hunan University of Science and Technology Xiangtan 400201 P. R. China.
RSC Chem Biol. 2025 Apr 29. doi: 10.1039/d5cb00024f.
Cisplatin and its analogs are extensively utilized as metal-based anticancer agents in clinical settings due to their mechanism of action, which involves targeting genomic double-stranded DNA to induce cytotoxicity in cancer cells. However, the associated severe side effects and DNA damage repair-inducing drug resistance present significant challenges. In recent years, G-quadruplex nucleic acids, formed through the self-assembly of guanine-rich nucleic acid sequences, have emerged as a compelling target for the design of novel anticancer therapeutics. The strategic design of platinum complexes that selectively interact with, stabilize, or cleave G-quadruplex structures represents a promising approach for developing effective anticancer agents to overcome cisplatin resistance. This review will emphasize the advancements made over the past decade in interacting G-quadruplexes with platinum complexes as potential anticancer therapeutics. The ongoing development of platinum complexes spans from targeting nuclear DNA G-quadruplexes to mitochondrial DNA and cytoplasmic RNA G-quadruplexes, evolving from monotherapy approaches, such as chemotherapy and photodynamic therapy, to a combination of radiotherapy, immunotherapy, and more, highlighting the dynamic progress of platinum complexes. At the end, we have summarized 4 points of pending issues in this fast-growing field, which we hope can provide some help to the development of this field.
顺铂及其类似物因其作用机制（涉及靶向基因组双链DNA以诱导癌细胞产生细胞毒性）而在临床环境中被广泛用作金属基抗癌药物。然而，相关的严重副作用以及DNA损伤修复诱导的耐药性带来了重大挑战。近年来，由富含鸟嘌呤的核酸序列自组装形成的G-四链体核酸已成为新型抗癌疗法设计的一个引人注目的靶点。选择性地与G-四链体结构相互作用、稳定或切割G-四链体结构的铂配合物的策略性设计，是开发有效抗癌药物以克服顺铂耐药性的一种有前景的方法。本综述将重点介绍过去十年中在将G-四链体与铂配合物相互作用作为潜在抗癌疗法方面取得的进展。铂配合物的不断发展从靶向核DNA G-四链体到线粒体DNA和细胞质RNA G-四链体，从化疗和光动力疗法等单一疗法发展到放疗、免疫疗法等多种疗法的联合，突出了铂配合物的动态进展。最后，我们总结了这个快速发展领域中有待解决的4个问题，希望能为该领域的发展提供一些帮助。
