双抗体靶向阿霉素纳米药物的研制及其靶向抗骨肉瘤作用  

Experimental study on the development and targeting effect of nanoparticles of double-antibody complex and adriamycin loaded

作　　者：郑亦静[1] 张小磊[1] 林焱[1] 武垚森[1] 张琼[1] 

机构地区：[1]温州医科大学附属第二医院骨科,浙江温州325027

出　　处：《温州医学院学报》2015年第8期547-551,共5页Journal of Wenzhou Medical College

基　　金：浙江省自然科学基金资助项目(Y2110466;Y2110467);温州市科技局科技计划项目(S20100048)

摘　　要：目的:合成双抗体(抗壳聚糖抗体、抗HER2抗体)-阿霉素-壳聚糖纳米粒,研究其体外肿瘤细胞摄取实验及骨肉瘤裸鼠体内的靶向特性。方法:采用壳聚糖衍生物乙二醇壳聚糖制备双抗体-阿霉素-壳聚糖(Abc-GC-Dox)纳米粒、阿霉素-壳聚糖纳米粒。在体外将药物作用于HER2+裸鼠骨肉瘤细胞系MG-63细胞,研究体外肿瘤细胞摄取实验,并采用免疫荧光的方法对其进行研究;14只骨肉瘤裸鼠随机分为2组,尾静脉注射不同药物,观察裸鼠体内皮下骨肉瘤的靶向分布差异。结果:本实验制得了稳定的双抗体靶向阿霉素纳米粒,包封率为89.73%,载药量为9.96%。通过体内外实验,双抗体纳米靶向药物的靶向聚集浓度明显高于无抗体纳米药物,差异有统计学意义(P<0.05)。结论:本实验成功制备了双抗体靶向阿霉素纳米药物(Abc-GC-Dox),并证明该双抗体纳米粒提高了抗肿瘤药物在骨肉瘤细胞内的靶向分布,明显提高了药物浓度,并降低了药物的不良反应,为临床治疗骨肉瘤提供了一种新的治疗方法。Objective：To synthesize double antibody complex-glycol chitosan doxorubicin nanoparticles（Abc-GC-Dox） and study its targeting effect of osteosarcoma in mice.Methods：Abc-GC-Dox and GC-Dox were prepared by emulsion polymerization method,in vitro immunofluorescence was used to study the intake test of HER2＋carried MG-63 cells in Abc-GC-Dox and GC-Dox.Fourteen mice with osteosarcoma were randomly divided into 2 groups.After corresponding treatment,different drugs（Abc-GC-Dox and GC-Dox） were given via tailvein,and the targeting effect was observed.Results：Stable Abc-GC-Dox and the quantity of drug · loading and entrapment were gotten.Compare to GC-Dox,there was a better drug concentration in osteosarcoma in mice,which showed a well targeting effect in vivo.Conclusion：Abc-GC-Dox is successfully developed and the nanoparticles demonstrated targeting aggregating distribution.In future,Abc-GC-Dox can be a potential drug for the clinical treatment of tumors.

关 键 词：双抗体联合 阿霉素 乙二醇壳聚糖 纳米粒 靶向治疗 骨肉瘤 裸鼠 

分 类 号：R730.53[医药卫生—肿瘤]