载阿霉素普朗尼克化聚酰胺-胺树状聚合物对乳腺癌多药耐药细胞株MCF-7/ADR的抑制作用

Inhibition of MCF-7/ADR cells by DOX-loaded pluronic-attached PAMAM dendrimer conjugate

本文合成了普朗尼克修饰的聚酰胺-胺聚合物(PF127-PAMAM),以阿霉素(DOX)为模型药物,考察了该载药复合物对乳腺癌多药耐药细胞株MCF-7/ADR的抑制作用。核磁共振图谱及红外图谱表明聚合物成功合成,元素分析法测得每个聚酰胺-胺分子伯氨基的普朗尼克化程度为27.63%(PAMAM∶PF127,1∶35.37,摩尔比)。PF127-PAMAM较PAMAM水合粒径增大,zeta电位有所降低。较低的电位及PF127的保护作用使得PF127-PAMAM有较低的溶血性和细胞毒性。每个PF127-PAMAM分子可以负载19.58个DOX分子,载药复合物的释放具有缓慢释放及pH敏感的特性。对于乳腺癌细胞株MCF-7,PF127-PAMAM/DOX的细胞毒性较游离DOX稍弱;而对于乳腺癌多药耐药细胞株MCF-7/ADR,PF127-PAMAM/DOX则表现出较强的逆转耐药性的效果,其耐药逆转指数(RRI)高达33.15。

Pluronic modified polyamidoamine （PAMAM） conjugate （PF127-PAMAM） was prepared and the inhibiting effect of MDR against MCF-7/ADR was investigated with doxorubicin （DOX） as model drug. 1H NMR and FTIR spectra showed that the conjugate was synthesized successfully. Element analysis accurately measured that 27.63% amino of per PAMAM was modified by pluronic （PAMAM ： PF127, 1 ： 35.37 mole ratio）. PF127-PAMAM showed an increased size and a reduced zeta potential compared to PAMAM. PF127-PAMAM had lower hemolytic toxicity and cytotoxicity due to the reduced zeta potential and the protection of PF127. Each PF127-PAMAM molecular could load 19.58 DOX molecules, and the complex exhibited sustained and pH-sensitive release behavior. PF127-PAMAM/DOX exhibited weaker cytotoxicity than free DOX in MCF-7 cells; while the complex showed much stronger reverse effect of drug resistance in MCF-7/ADR cells, and resistance reversion index （RRI） was as high as 33.15.