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首页> 外文期刊>Journal of biomedical materials research. Part B, Applied biomaterials. >Distinctive polymer micelle designed for siRNA delivery and reversal of MDR1 MDR1 gene‐dependent multidrug resistance
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Distinctive polymer micelle designed for siRNA delivery and reversal of MDR1 MDR1 gene‐dependent multidrug resistance

机译:专为siRNA递送和逆转MDR1 MDR1基因依赖性多药耐性而设计的独特聚合物胶束

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摘要

Abstract P‐glycoprotein (P‐gp) plays an importantrole in multidrug resistance (MDR), proved to be one of the major obstacles in cancer chemotherapy. Cationic polymers could specifically deliver siRNA to tumor cells and thus reverse MDR by the downregulation of P‐gp. In this study, a triblock copolymer micelle was prepared based on the polymer of N ‐succinyl‐chitosan–poly‐ l ‐lysine–palmitic acid (NSC–PLL–PA) to deliver siRNA–P‐gp (siRNA‐micelle) or doxorubicin (Dox‐micelle). The resulting micelle exhibited an efficient binding ability for siRNA and high encapsulation efficiency for Dox, with an average particle size of ~170?nm. siRNA‐micelle and Dox‐micellewere instable at low pH, thereby enhancing tumor accumulation and intracellular release of the encapsulated siRNA and Dox. siRNA‐micelle micelles could enhance the knockdown efficacy of siRNA by improving the transfection efficiency, downregulating P‐gp expression, and passing the drug efflux transporters, thereby improving the therapeutic effects of Dox‐micelle. However, P‐gp could transfer from HepG2/ADM to HepG2 cells independent of the expression of mdr1, and the acquired resistance could permit tumor cells to survive and develop intrinsic P‐gp‐mediated resistance, thereby limiting the desired efficiency of chemotherapeutics. This study demonstrated the effectiveness of siRNA‐micelle for tumor‐targeted delivery, MDR reversal, and provided an effective strategy for the treatment of cancers that develop MDR. ? 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 2093–2106, 2017.
机译:摘要p-糖蛋白(P-GP)在多药耐药性(MDR)中起着重要的是,证明是癌症化疗的主要障碍之一。阳离子聚合物可以专门将siRNA递送至肿瘤细胞,从而通过P-GP的下调反转MDR。在该研究中,基于N-索琥珀酰 - 壳聚糖 - 多溶胶 - 棕榈酸(NSC-PLL-PA)的聚合物制备三嵌段共聚物胶束,以递送siRNA-P-GP(siRNA-胶束)或多柔比星(DOX-MICELLE)。所得到的胶束表现出具有SiRNA的高效结合能力和用于DOX的高封装效率,平均粒度为约170μm。 SiRNA-MICELLE和DOX-MICELLEWERE在低pH下稳定,从而提高肿瘤积聚和包封的siRNA和DOX的细胞内释放。 SiRNA-MICELLE胶束可以通过改善转染效率,下调P-GP表达和通过药物流出转运蛋白来增强siRNA的敲低疗效,从而提高DOX-MICELLE的治疗效果。然而,P-GP可以独立于MDR1的表达转移到HepG2细胞,并且所获得的抗性可以允许肿瘤细胞存活并发展内在的P-GP介导的抗性,从而限制了化学治疗剂的所需效率。本研究表明siRNA-胶束用于肿瘤靶向递送,MDR逆转的有效性,并为制定MDR的癌症提供了有效的策略。还2016 Wiley期刊,Inc.J生物保解员B部分B:Appl Biomater,105B:2093-2106,2017。

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  • 作者单位

    Department of Pharmaceutics College of Pharmaceutical SciencesSoochow UniversitySuzhou People's;

    Department of Pharmaceutics College of Pharmaceutical SciencesSoochow UniversitySuzhou People's;

    Department of Pharmaceutics College of Pharmaceutical SciencesSoochow UniversitySuzhou People's;

    Department of Pharmaceutics College of Pharmaceutical SciencesSoochow UniversitySuzhou People's;

    Department of Pharmaceutics College of Pharmaceutical SciencesSoochow UniversitySuzhou People's;

    Department of Pharmaceutics College of Pharmaceutical SciencesSoochow UniversitySuzhou People's;

    Department of Pharmaceutics College of Pharmaceutical SciencesSoochow UniversitySuzhou People's;

    Department of Pharmaceutics College of Pharmaceutical SciencesSoochow UniversitySuzhou People's;

    College of Radiological Medicine and ProtectionSoochow UniversitySuzhou People's Republic of China;

    The Hospital of Suzhou People's Hospital Affiliated to Nanjing Medical UniversitySuzhou People's;

    Department of Pharmaceutics College of Pharmaceutical SciencesSoochow UniversitySuzhou People's;

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  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 医用一般科学;
  • 关键词

    cationic triblock copolymer; siRNA; multidrug resistance; micelle;

    机译:阳离子三嵌段共聚物;siRNA;多药耐药;胶束;

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