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首页> 外文期刊>Acta biomaterialia >Polypeptide-based combination of paclitaxel and cisplatin for enhanced chemotherapy efficacy and reduced side-effects
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Polypeptide-based combination of paclitaxel and cisplatin for enhanced chemotherapy efficacy and reduced side-effects

机译：紫杉醇和顺铂基于多肽的组合可增强化疗效果并减少副作用

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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：制备了一种新型的甲氧基聚（乙二醇）-b-聚（1-谷氨酸）-b-聚（1-苯丙氨酸）（mPEG-bP（Glu）-bP（Phe））三嵌段共聚物并作为胶束载体进行了研究共同递送紫杉醇（PTX）和顺铂（cis-diamminedichlo-platinum，CDDP）。 PTX和CDDP分别装载在疏水性P（Phe）内核内部并螯合到中间P（Glu）壳中，而mPEG为延长循环提供了外部电晕。载有PTX + CDDP的胶束的体外释放曲线表明，CDDP螯合交联阻止了PTX的初始爆发释放。载有PTX + CDDP的胶束在72 h的孵育过程中对A549人肺癌细胞系增殖具有抑制作用。对于异种移植人肺肿瘤的体内治疗，载有PTX + CDDP的胶束具有明显的抑瘤作用，抑瘤率（TSR％）为83.1％，显着高于游离药物组合或胶束结合的抑瘤率。单一药物。另外，更重要的是，载有PTX + CDDP的胶束的增强的抗肿瘤功效具有减少的副作用。在载有PTX + CDDP的胶束处理A549荷瘤小鼠期间，没有出现明显的体重减轻。因此，PTX和CDDP的基于多肽的组合可为有效和安全的癌症化疗提供有用的指导。

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