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基于共递药策略的纳米药物以克服顺铂耐药性。

Nanodrugs based on co-delivery strategies to combat cisplatin resistance.

机构信息

College of Chemistry and Chemical Engineering, College of Materials Science and Engineering, Institute of Biomedical Materials and Engineering, Qingdao University, Qingdao 266071, China.

College of Chemistry and Chemical Engineering, College of Materials Science and Engineering, Institute of Biomedical Materials and Engineering, Qingdao University, Qingdao 266071, China; State Key Laboratory of Bio-Fibers and Eco-Textiles, Qingdao University, Qingdao 266071, China.

出版信息

J Control Release. 2024 Jun;370:14-42. doi: 10.1016/j.jconrel.2024.04.020. Epub 2024 Apr 17.

Abstract

Cisplatin (CDDP), as a broad-spectrum anticancer drug, is able to bind to DNA and inhibit cell division. Despite the widespread use of cisplatin since its discovery, cisplatin resistance developed during prolonged chemotherapy, similar to other small molecule chemotherapeutic agents, severely limits its clinical application. Cisplatin resistance in cancer cells is mainly caused by three reasons: DNA repair, decreased cisplatin uptake/increased efflux, and cisplatin inactivation. In earlier combination therapies, the emergence of multidrug resistance (MDR) in cancer cells prevented the achievement of the desired therapeutic effect even with the accurate combination of two chemotherapeutic drugs. Therefore, combination therapy using nanocarriers for co-delivery of drugs is considered to be ideal for alleviating cisplatin resistance and reducing cisplatin-related toxicity in cancer cells. This article provides an overview of the design of cisplatin nano-drugs used to combat cancer cell resistance, elucidates the mechanisms of action of cisplatin and the pathways through which cancer cells develop resistance, and finally discusses the design of drugs and related carriers that can synergistically reduce cancer resistance when combined with cisplatin.

摘要

顺铂(CDDP)作为一种广谱抗癌药物,能够与 DNA 结合并抑制细胞分裂。尽管自发现以来顺铂已被广泛应用,但与其他小分子化疗药物类似,其在长期化疗过程中产生的耐药性严重限制了其临床应用。癌细胞中的顺铂耐药性主要由以下三个原因引起:DNA 修复、顺铂摄取减少/流出增加以及顺铂失活。在早期的联合治疗中,即使两种化疗药物的组合准确无误,癌细胞中多药耐药性(MDR)的出现也阻止了达到理想的治疗效果。因此,使用纳米载体联合递送药物的联合治疗被认为是缓解顺铂耐药性和降低癌细胞中顺铂相关毒性的理想方法。本文概述了用于对抗癌细胞耐药性的顺铂纳米药物的设计,阐明了顺铂的作用机制以及癌细胞产生耐药性的途径,最后讨论了与顺铂联合使用时可以协同降低癌症耐药性的药物和相关载体的设计。

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