Autophagy-targeted Pt(iv) agents: a new horizon in antitumor drug development

IF 3.5 3区 化学 Q2 CHEMISTRY, INORGANIC & NUCLEAR
Suying Li, Yan Chen, Shuaiqi Feng, Zhifang Liu, Linling Gan and Qingpeng Wang
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引用次数: 0

Abstract

Pt(IV) complexes as prodrugs of Pt(II) drugs exhibit numerous advantages such as enhanced stability, reduced toxicity, increased oral bioavailability, and efficacy in overcoming the drug resistance of Pt(II) compounds, which underscore their significant potential in the advancement of novel Pt anticancer agents. Furthermore, protective autophagy is pivotal in sustaining tumor cell homeostasis and modulating the tumor microenvironment (TME), thereby representing a critical target for the development of antitumor drugs. Specific inhibition or activation of autophagy during chemotherapy would break the internal homeostasis in the TME and increase antitumor activities. Consequently, developing novel Pt(IV) antitumor agents with autophagy-targeting capabilities by incorporating autophagy-regulating moieties into the Pt(IV) framework has emerged as a hot topic in the discovery of novel Pt drugs. Herein, the research progress in novel Pt(IV) antitumor drugs with autophagy-targeted properties is systematically reviewed based on the literature. The future challenges and perspectives of this fascinating class of conjugates are also discussed, aiming to provide new insights and approaches for the future design and investigation of novel Pt antitumor drugs.

Abstract Image

靶向自噬的铂(IV)药物:抗肿瘤药物开发的新领域
Pt(IV)配合物作为Pt(II)药物的前药,具有稳定性增强、毒性降低、口服生物利用度提高、克服Pt(II)化合物耐药等诸多优点,在开发新型Pt抗癌药物方面具有重要潜力。此外,保护性自噬在维持肿瘤细胞稳态和调节肿瘤微环境(TME)中起着关键作用,因此是抗肿瘤药物开发的重要靶点。化疗过程中特异性抑制或激活自噬可打破TME内部稳态,增强抗肿瘤活性。因此,通过将自噬调节基团纳入Pt(IV)框架,开发具有自噬靶向能力的新型Pt(IV)抗肿瘤药物已成为发现新型Pt药物的热点。本文在文献综述的基础上,系统综述了具有自噬靶向特性的新型铂(IV)抗肿瘤药物的研究进展。讨论了这类极具吸引力的缀合物的未来挑战和前景,旨在为未来新型Pt抗肿瘤药物的设计和研究提供新的见解和方法。
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来源期刊
Dalton Transactions
Dalton Transactions 化学-无机化学与核化学
CiteScore
6.60
自引率
7.50%
发文量
1832
审稿时长
1.5 months
期刊介绍: Dalton Transactions is a journal for all areas of inorganic chemistry, which encompasses the organometallic, bioinorganic and materials chemistry of the elements, with applications including synthesis, catalysis, energy conversion/storage, electrical devices and medicine. Dalton Transactions welcomes high-quality, original submissions in all of these areas and more, where the advancement of knowledge in inorganic chemistry is significant.
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