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首页> 外文期刊>Advanced drug delivery reviews >Pluronic block copolymers for overcoming drug resistance in cancer.
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Pluronic block copolymers for overcoming drug resistance in cancer.

机译：用于克服癌症耐药性的Pluronic嵌段共聚物。

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摘要

Pluronic block copolymers have been used extensively in a variety of pharmaceutical formulations including delivery of low molecular mass drugs and polypeptides. This review describes novel applications of Pluronic block copolymers in the treatment of drug-resistant tumors. It has been discovered that Pluronic block copolymers interact with multidrug-resistant cancer (MDR) tumors resulting in drastic sensitization of these tumors with respect to various anticancer agents, particularly, anthracycline antibiotics. Furthermore, Pluronic affects several distinct drug resistance mechanisms including inhibition of drug efflux transporters, abolishing drug sequestration in acidic vesicles as well as inhibiting the glutathione/glutathione S-transferase detoxification system. All these mechanisms of drug resistance are energy-dependent and therefore ATP depletion induced by Pluronic block copolymers in MDR cells is considered as one potential reason for chemosensitization of these cells. Following validation using in vitro and in vivo models, a formulation containing doxorubicin and Pluronic mixture (L61 and F127), SP1049C, has been evaluated in phase I clinical trials. Further mechanistic studies and clinical evaluations of these systems are in progress.
机译：Pluronic嵌段共聚物已广泛用于包括低分子量药物和多肽的输送在内的多种药物制剂中。这篇综述描述了Pluronic嵌段共聚物在抗药性肿瘤治疗中的新应用。已经发现，Pluronic嵌段共聚物与多药抗性癌症（MDR）肿瘤相互作用，导致这些肿瘤对各种抗癌剂，特别是蒽环类抗生素的急剧敏化。此外，Pluronic影响几种独特的耐药机制，包括抑制药物外排转运蛋白，废除酸性囊泡中的药物螯合以及抑制谷胱甘肽/谷胱甘肽S-转移酶解毒系统。所有这些耐药性机制都是能量依赖性的，因此Pluronic嵌段共聚物在MDR细胞中诱导的ATP消耗被认为是这些细胞化学增敏的潜在原因之一。使用体外和体内模型进行验证后，已在I期临床试验中评估了含有阿霉素和Pluronic混合物（L61和F127）SP1049C的制剂。这些系统的进一步机理研究和临床评估正在进行中。

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