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Polypeptide-based combination of paclitaxel and cisplatin for enhanced chemotherapy efficacy and reduced side-effects

机译：基于多肽的紫杉醇和顺铂的组合，增强化疗疗效和副作用减少

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摘要

A novel methoxy poly(ethylene glycol)-b-poly(l-glutamic acid)-b-poly(l-phenylalanine) (mPEG-b-P(Glu)-b-P(Phe)) triblock copolymer was prepared and explored as a micelle carrier for the co-delivery of paclitaxel (PTX) and cisplatin (cis-diamminedichlo-platinum, CDDP). PTX and CDDP were loaded inside the hydrophobic P(Phe) inner core and chelated to the middle P(Glu) shell, respectively, while mPEG provided the outer corona for prolonged circulation. An in vitro release profile of the PTX + CDDP-loaded micelles showed that the CDDP chelation cross-link prevented an initial burst release of PTX. The PTX + CDDP-loaded micelles exhibited a high synergism effect in the inhibition of A549 human lung cancer cell line proliferation over 72 h incubation. For the in vivo treatment of xenograft human lung tumor, the PTX + CDDP-loaded micelles displayed an obvious tumor inhibiting effect with a 83.1% tumor suppression rate (TSR%), which was significantly higher than that of a free drug combination or micelles with a single drug. In addition, more importantly, the enhanced anti-tumor efficacy of the PTX + CDDP-loaded micelles came with reduced side-effects. No obvious body weight loss occurred during the treatment of A549 tumor-bearing mice with the PTX + CDDP-loaded micelles. Thus, the polypeptide-based combination of PTX and CDDP may provide useful guidance for effective and safe cancer chemotherapy.
机译：一种新颖的甲氧基聚（乙二醇） - 嵌段 - 聚（L-谷氨酸） - 嵌段 - 聚（L-苯丙氨酸）（MPEG-BP（谷氨酸）-bP丙氨酸（Phe））制备三嵌段共聚物，并探讨作为胶束载体紫杉醇的共递送（PTX）和顺铂（顺式 - diamminedichlo铂，CDDP）。 PTX和CDDP分别加载疏水性P（苯丙氨酸）内芯的内部和螯合到中间P（GLU）壳，而的mPEG提供用于延长循环中的外部电晕。的PTX + CDDP加载的胶束的体外释放曲线表明，CDDP螯合交联防止PTX的初始突释。的PTX + CDDP加载胶束显示出的A549人肺癌细胞系增殖的抑制超过72小时的温育高的协同作用效果。用于体内治疗异种移植人肺肿瘤中，PTX + CDDP加载胶束显示明显的肿瘤抑制与83.1％的肿瘤抑制率（TSR％），这是显著高于游离药物组合或胶束的效果单一药物。此外，更重要的是，PTX + CDDP加载胶束的增强的抗肿瘤功效附带减少副作用。治疗A549肿瘤的小鼠与PTX + CDDP加载胶束过程中没有发生明显的体重丢失。因此，PTX和CDDP的基于多肽的组合可以提供有效而安全的癌症化疗有用的指导。

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  • 来源
    《Acta biomaterialia》 |2014年第3期|共11页
  • 作者

    SongW.; TangZ.; LiM.; LvS.; SunH.; DengM.; LiuH.; ChenX.;

  • 作者单位

    Key Laboratory of Polymer Ecomaterials Changchun Institute of Applied Chemistry Chinese Academy;

    Key Laboratory of Polymer Ecomaterials Changchun Institute of Applied Chemistry Chinese Academy;

    Key Laboratory of Polymer Ecomaterials Changchun Institute of Applied Chemistry Chinese Academy;

    Key Laboratory of Polymer Ecomaterials Changchun Institute of Applied Chemistry Chinese Academy;

    Key Laboratory of Polymer Ecomaterials Changchun Institute of Applied Chemistry Chinese Academy;

    Department of Chemistry Northeast Normal University Changchun 130022 China;

    Laboratory Animal Center Jilin University Changchun 130012 China;

    Key Laboratory of Polymer Ecomaterials Changchun Institute of Applied Chemistry Chinese Academy;

  • 收录信息
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 普通生物学;
  • 关键词

    Cisplatin; Combination chemotherapy; Paclitaxel; Polypeptide;

    机译：顺铂;组合化疗;紫杉醇;多肽;

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