携紫杉醇和抗人表皮生长因子受体2抗体高分子造影剂的制备及体外寻靶实验研究  

Preparation of paclitaxel loaded and human epidermal growth factor receptor-2-targeted macromolecular contrast agent and targeting research in vitro

作　　者：温卿 闫国珍[1] 何俊峰[1] 刘扬[1] Wen Qing;Yan Guozhen;He Junfeng;Liu Yang(Department of Ultrasound,The First Affiliated Hospital of Baotou Medical College,Baotou 014010,China)

机构地区：[1]包头医学院第一附属医院超声科,014010

出　　处：《中华医学超声杂志（电子版）》2018年第6期473-478,共6页Chinese Journal of Medical Ultrasound(Electronic Edition)

基　　金：内蒙古自治区研究生科研创新项目[S201610127(Y04)]

摘　　要：目的制备一种携紫杉醇和抗人表皮生长因子受体2(HER-2)抗体的高分子造影剂,并考察其体外寻靶能力及体外显像效果。方法通过双乳化法及碳二亚胺法制备携紫杉醇和抗HER-2抗体的高分子造影剂,并对其一般性质进行检测,激光共聚焦显微镜观察制备的靶向载药造影剂与SKBR-3乳腺癌细胞的结合能力,并使用高频超声观察其体外显影效果。结果载药靶向羧基端乳酸(PLGA)纳米粒平均粒径为(318.07±12.51)nm,表面电位(-2.16±0.31)m V,包封率为(60.00±3.40)%,载药量为(6.00±0.34)%,粒子呈规则球形,大小均一,分散性好。激光共聚焦显微镜观察到抗HER-2抗体和羧基端乳酸-羟基乙酸共聚物(PLGA-COOH)造影剂大量结合,流式细胞术观察到两者的结合率高达(99.59±0.42)%,体外寻靶实验示靶向载药高分子超声造影剂与SBKR-3乳腺癌细胞较强的结合在一起。体外成像实验显示,靶向载药高分子造影剂显像呈细腻均匀点状强回声。结论成功制备了携抗HER-2抗体和紫杉醇高分子造影剂,该纳米粒相关性能良好,有较高的载药量及包封率,且与高表达HER-2受体的乳腺癌细胞有较强结合能力,有较好的体外显像效果。Objective To prepare a high molecular contrast agent carrying paclitaxel and anti human epidermal growth factor receptor-2(HER-2)antibody,and to investigate the target ability in vitro and its effects on ultrasonography in vitro.Methods The paclitaxel-loaded and anti HER-2 antibodies polymer contrast agents were prepared by the double emulsion technique and carbodiimide technique,and its general properties were by tested.The combination of drug-loading targeted contrast agent and SKBR-3 breast cancer cells was observed with laser confocal microscope.The effect of imaging in vitro was observed by the high frequency ultrasonography.Results The average diameter of drug-loaded targeting carboxyl terminal lactic acid(PLGA)nanoparticle was(318.07±12.51)nm,the surface potential was(-2.16±0.31)mV,the drug encapsulation efficiency was(60.00±3.40)%,the drug loading amounts was(6.00±0.34)%,and the contrast agent was spherical particles with uniform size and good dispersion.Laser confocal microscope found significant combination of anti HER-2 antibody and carboxyl terminal lactic acid/hydroxyacetic acid copolymer(PLGA-COOH)polymer contrast agent.Flow cytometry observed the combination rate was(99.59±0.42)%.Search target experiment in vitro observed drug targeting macromolecular contrast agent and SBKR-3 breast cancer cells had a high binding rate.In vitro imaging experiments showed that drug targeting macromclecular imgaging agent appeared uniform and fine dotted dense hyper-echogenicity.Conclusions A kind of her-2-targeted and paclitaxel loaded high molecular contrast agent was successfully prepared.It had good performance,high drug loading amounts and entrapment efficiency.It and SKBR-3 breast cancer cells had a high binding rate.The external imaging was better.

关 键 词：高分子造影剂 抗人表皮生长因子受体2抗体 紫杉醇 

分 类 号：R943[医药卫生—药剂学]