Song Wantong, Tang Zhaohui, Li Mingqiang, Lv Shixian, Sun Hai, Deng Mingxiao, Liu Huaiyu, Chen Xuesi
Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, People's Republic of China.
Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, People's Republic of China.
Acta Biomater. 2014 Mar;10(3):1392-402. doi: 10.1016/j.actbio.2013.11.026. Epub 2013 Dec 6.
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.
制备了一种新型的甲氧基聚（乙二醇）-b-聚（L-谷氨酸）-b-聚（L-苯丙氨酸）（mPEG-b-P(Glu)-b-P(Phe)）三嵌段共聚物，并将其作为紫杉醇（PTX）和顺铂（顺二氨二氯铂，CDDP）共递送的胶束载体进行研究。PTX和CDDP分别负载在疏水的P(Phe)内核中并螯合到中间的P(Glu)壳层上，而mPEG提供外层冠层以实现延长循环。负载PTX+CDDP的胶束的体外释放曲线表明，CDDP螯合交联阻止了PTX的初始突释。负载PTX+CDDP的胶束在72小时孵育期间对A549人肺癌细胞系增殖的抑制中表现出高协同效应。对于异种移植人肺肿瘤的体内治疗，负载PTX+CDDP的胶束显示出明显的肿瘤抑制作用，肿瘤抑制率（TSR%）为83.1%，显著高于游离药物组合或单药胶束。此外，更重要的是，负载PTX+CDDP的胶束增强的抗肿瘤功效伴随着副作用的减少。在用负载PTX+CDDP的胶束治疗携带A549肿瘤的小鼠期间，未发生明显的体重减轻。因此，基于多肽的PTX和CDDP组合可为有效且安全的癌症化疗提供有用的指导。
