In vitro evaluation of anticancer nanomedicines based on doxorubicin and amphiphilic Y-shaped copolymers.
In vitro evaluation of anticancer nanomedicines based on doxorubicin and amphiphilic Y-shaped copolymers.
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基于阿霉素和两亲性Y形共聚物的抗癌纳米药物的体外评价
DOI：
10.2147/ijn.s30687
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发表时间：
2012
影响因子：
8
通讯作者：
Chen XS
中科院分区：
文献类型：
--
作者：
Li D;Ding JX;Tang ZH;Sun H;Zhuang XL;Xu JZ;Chen XS
以双羟基功能化聚乙交酯为大分子引发剂，辛酸亚锡为催化剂，以L丙交酯和乙交酯为原料，通过开环聚合合成了4种单甲氧基聚乙二醇聚(L丙交酯-乙交酯共聚)2(mEg-P(LA-co-GA)2)。在pH为7.4的磷酸盐缓冲液中，共聚物自组装成纳米尺度的胶束/囊泡聚集体。将抗癌药物多柔比星(DOX)负载到胶束/囊泡纳米粒中，得到胶束/囊泡纳米药物。疏水聚酯的含量和释放介质的pH值可以调节其体外释放行为。体外细胞实验表明，P(LA-co-GA)的含量可以调节DOX在细胞内的释放，不同培养时间的纳米药物对Henrietta Lks‘s细胞表现出有效的增殖抑制作用。溶血实验表明，共聚物具有良好的血液相容性，共聚物的存在可显著降低DOX的溶血率。这些结果表明，基于DOX和两亲性Y形共聚物的新型抗癌纳米药物是有吸引力的体内肿瘤组织和细胞内靶向给药系统，具有更高的循环稳定性和靶点的药物释放速度。
Four monomethoxy poly(ethylene glycol)-poly(L-lactide-co-glycolide)2 (mPEG-P( LA-co-GA)2) copolymers were synthesized by ring-opening polymerization of L-lactide and glycolide with double hydroxyl functionalized mPEG (mPEG-(OH)2) as macroinitiator and stannous octoate as catalyst. The copolymers self-assembled into nanoscale micellar/vesicular aggregations in phosphate buffer at pH 7.4. Doxorubicin (DOX), an anthracycline anticancer drug, was loaded into the micellar/vesicular nanoparticles, yielding micellar/vesicular nanomedicines. The in vitro release behaviors could be adjusted by content of hydrophobic polyester and pH of the release medium. In vitro cell experiments showed that the intracellular DOX release could be adjusted by content of P(LA-co-GA), and the nanomedicines displayed effective proliferation inhibition against Henrietta Lacks’s cells with different culture times. Hemolysis tests indicated that the copolymers were hemocompatible, and the presence of copolymers could reduce the hemolysis ratio of DOX significantly. These results suggested that the novel anticancer nanomedicines based on DOX and amphiphilic Y-shaped copolymers were attractive candidates as tumor tissular and intracellular targeting drug delivery systems in vivo, with enhanced stability during circulation and accelerated drug release at the target sites.