载紫杉醇肝素纳米粒-微泡复合物优化构建及对于不同乳腺癌细胞株超声作用条件的筛选  

Optimal preparation of the complex of paclitaxel loaded heparin nanoparticles and microbubbles and screening for the optimized ultrasound condition for different breast cancer cells

作　　者：罗婉贤 王冬晓 张霞 杨莉[2] 王莺[3] 张丽[1] 马菲[1] 张世玉[1] 李颖嘉[1] 

机构地区：[1]南方医科大学南方医院超声科,广州510515 [2]南方医科大学南方医院药剂科,广州510515 [3]南方医科大学南方医院肿瘤研究所,广州510515 [4]不详

出　　处：《中华超声影像学杂志》2016年第4期356-361,共6页Chinese Journal of Ultrasonography

基　　金：国家自然科学基金面上项目，广东省科技计划项目(2011B010400018,2013B010404024)National Natural Science Foundation of China General Program，Science and Technology Planning Project of Guangdong Province of China

摘　　要：目的探讨构建载紫杉醇肝素纳米粒-微泡复合物体系的优化条件，筛选该体系作用于高侵袭性人乳腺癌细胞株MDA-MB-231及低侵袭性人乳腺癌细胞株MCF-7的适宜超声辐照参数。方法以肝素为原料制备生物素化的载紫杉醇肝素纳米粒，机械震荡法制备生物素化脂质微泡，选取不同浓度的载紫杉醇纳米粒借助生物素-亲和素桥与脂质微泡结合形成载紫杉醇肝素纳米粒-微泡复合物，计算其载药量，得出其最佳配比。不同的超声辐照声强及辐照时间分别作用于高侵袭性人乳腺癌细胞株MDA—MB-231及低侵袭性人乳腺癌细胞株MCF-7，荧光显微镜下观察纳米粒摄取情况，筛选不同乳腺癌细胞株适宜超声辐照条件。结果载紫杉醇纳米粒的浓度为2mg／ml时，载紫杉醇肝素纳米粒-微泡复合物的载药量最高，每10^8个复合物载紫杉醇106．7μg。载紫杉醇肝素纳米粒-微泡复合物作用于MDA-MB-231细胞的最佳超声辐照条件为辐照声强1．0W／cm2，辐照时间40S；作用于MCF-7细胞的最佳超声辐照条件为辐照声强1．5w／cm2，辐照时间40S。结论成功构建具有较好药物运载性能的载紫杉醇肝素纳米粒-微泡复合物体系，该体系作用于不同性能的乳腺癌细胞株，超声作用条件存在差异。Objective To investigate the optimal preparation of the complex of paclitaxel- loaded heparin nanoparticles and microbubbles and screen the optimized ultrasound （US） condition for highly aggressive breast cancer cells MDA-MB-231 and less aggressive breast cancer cells MCF-7. Methods Paclitaxel-loaded nanoparticles were prepared using heparin as nanocarrier, and biotinlyated microbubbles were prepared by mechanical shaking. Paclitaxel-loaded nanoparticles was conjugated with microbubbles to prepare the complex using avidin-biotin system. The optimized method was screened. Breast cancer cell MDA-MB-231 and MCF-7 were treated with the prepared complex and different ultrasonic parameters including irradiation intensity and exposure duration were evaluated by cellular uptake experiments. Results The drug loading in the complex was 106.7 μg/108 microbubbles when the paclitaxel-nanoparticle concentration was 2 mg/ml. For MDA-MB-231 cells, the optimal irradiation intensity was 1.0 W/cm2 and the optimal exposure duration was 40 s, and they were 1.5W/cm2 and 40s for MCF-7 cells, respectively. Conclusions The complex with high drug loading weight, composed of paclitaxelqoaded heparin nanoparticles and microbubbles, was successfully prepared, and it was found the optimal ultrasound condition was different in two breast cancer cells.

关 键 词：超声检查 紫杉醇纳米粒 微气泡 肿瘤细胞 

分 类 号：R73-3[医药卫生—肿瘤] R445.1[医药卫生—临床医学]