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过渡金属配合物抗肿瘤级联靶向策略

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以顺铂为代表的铂类药物在临床上的成功,使金属配合物的抗肿瘤特性逐渐进入大众视野,但靶向性缺失与多药耐药性制约了金属药物的发展.因此,如何获得高效低毒的新型抗肿瘤金属配合物是目前研究的关键.过渡金属结构易修饰,可以通过合理引入不同功能的有机配体,改变金属配合物的亚细胞器分布及生物分子靶标,激活与经典铂药不同的抗肿瘤机制.本文综述了近年来通过级联靶向策略实现从亚细胞器富集到生物大分子靶向及干预的金属配合物,并对其抗肿瘤机制进行了归纳总结,希望通过本文可以对未来靶向金属药物的设计提供新的研究基础与启发.
Cascade targeting strategy for antitumor transition metal complexes
The clinical efficacy of platinum drugs,such as cisplatin,has gradually attracted public attention to the anti-tumor properties of metal complexes.However,the lack of targeted delivery and development of multi-drug resistance have impeded the progress in metal-based therapeutics.The current research focus is on obtaining novel antitumor metal complexes that demonstrate high efficacy and low toxicity.One crucial aspect being explored is the facile modification characteristic inherent to transition metal structures.By strategically introducing diverse organic ligands,it becomes possible to modulate sub-organelle localization and biomolecular targets of these metal complexes,thereby activating distinct anti-tumor mechanisms compared to platinum drugs.This review aims to summarize recent advancements in cascade targeting strategies for achieving sub-organelle enrichment and biomacromolecule targeting with metal complexes while elucidating their respective anti-tumor mechanisms.It is anticipated that this paper will provide a new research foundation and inspiration for future design endeavors focused on targeted metal-based therapeutics.

transition metal complexessubcellular targetingbiomolecular regulationantitumor therapy

郑越、刘文婷、曹乾、谭彩萍、夏炜、毛宗万

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中山大学化学学院,生物无机与合成化学教育部重点实验室,广州 510006

过渡金属配合物 亚细胞器靶向 生物分子调控 抗肿瘤治疗

国家重点研发计划国家自然科学基金资助项目国家自然科学基金资助项目广州市科技计划项目

2022YFB380450222293053221071242024A04J4511

2024

中国科学(化学)
中国科学院

中国科学(化学)

CSTPCD北大核心
影响因子:0.685
ISSN:1674-7224
年,卷(期):2024.54(9)