葡聚糖分子量和接枝度对阿霉素／白蛋白-葡聚糖纳米粒子体外抗肿瘤效果的影响  

In Vitro Anticancer Effects of Doxorubicin Loaded BSA-dextran Nanoparticles with Different Molecular Weights of Dextran and Different Dextran Conjugation Degrees

作　　者：郝和群[1,2] 姚萍[1] 

机构地区：[1]复旦大学聚合物分子工程国家重点实验室 高分子科学系,上海200433 [2]皖西学院基础实验中心,六安237012

出　　处：《高等学校化学学报》2014年第3期652-659,共8页Chemical Journal of Chinese Universities

基　　金：国家重点基础研究发展计划(批准号:2011CB932503);国家自然科学基金(批准号:21274026)资助~~

摘　　要：以Maillard反应制备的牛血清白蛋白-葡聚糖共价接枝物作为载体,通过调节混合溶液的pH值和温度制备负载阿霉素的白蛋白-葡聚糖纳米粒子.利用分子量为5×10^3,10×10^3和62×10^3的葡聚糖制备了多种共价接枝物,研究了共价接枝物分子量对载药纳米粒子的粒径和稳定性及载药量的影响.用短链葡聚糖（分子量5×10^3和10×10^3）制备的纳米粒子粒径为60 nm左右,用长链葡聚糖（分子量62×10^3）制备的纳米粒子粒径约为200 nm；阿霉素的包埋效率为81%-98%,包埋量为7.4%-16.9%.细胞实验结果表明,共价接枝物具有很好的生物相容性；与自由阿霉素相比,纳米粒子可以促进阿霉素进入人口腔上皮癌细胞；受缓释性质的影响,纳米粒子在低浓度时的细胞毒性要小于自由阿霉素.与长链葡聚糖纳米粒子相比,接枝度高的短链葡聚糖纳米粒子由于具有较小的粒径、密集的葡聚糖分子刷表面、一定的自由阿霉素浓度和较快的阿霉素释放速率,因而更容易进入细胞并具有更好的体外抗肿瘤活性.Bovine Sercurn albumin-dextran（ BSA-dextran） conjugates were prepared with different molecular weights of dextran and different molar ratios of BSA to dextran via Maillard reaction. Doxorubicin loaded BSA-dextran nanoparticles were fabricated by changing the pH and then temperature of the mixture. The nanoparti-cles with 5í103 and 10×10^3 dextran have a size about 60 nm, and the nanoparticles with 62×10^3 dextran have a size about 200 nm. The doxorubicin loading efficiency is in the range of 81%-98%, and the loading amount is 7.4%-16.9%. In vitro cell viability investigation confirms the excellent biocompatibility of BSA-dextran conjugates. Compared with free doxorubicin, the nanoparticles can enhance the cellular internalization of the loaded doxorubicin and they show lower anticancer activity at lower doxorubicin concentrations because of the slower release of the loaded doxorubicin. In comparison with the nanoparticles with 62×10^3 and 10×10^3 dextran, the nanoparticles with 5×10^3 dextran and higher dextran conjugation degree show better cellular inter-nalization and better anticancer activity in vitro due to their smaller size, denser dextran brush surface, certain free doxorubicin concentration, and faster release rate of the loaded doxorubicin.

关 键 词：葡聚糖 牛血清白蛋白 药物释放 纳米粒子 抗肿瘤活性 阿霉素 

分 类 号：O636[理学—高分子化学] O629[理学—化学]