新型负载多柔比星纳米基因载体的研制及其对骨肉瘤细胞的抑制效应  

Development of novel adriamycin-loaded nanoparticles and its inhibitory effect on osteosarcoma cells

作　　者：孙廓[1] 陈统一[2] 王靖[3] 张键[2] 

机构地区：[1]南昌大学第二附属医院骨科,南昌330006 [2]复旦大学附属中山医院骨科,上海200032 [3]华东理工大学材料与工程学院,上海200237

出　　处：《中国新药杂志》2016年第9期1061-1068,共8页Chinese Journal of New Drugs

基　　金：江西省科技厅科技社会发展项目(20122BBG70107-3);江西省卫生计生委科技计划(20155278)

摘　　要：目的:研究制备葡聚糖(DEX)-多柔比星(ADM)-聚乙烯亚胺(PEI)纳米材料,同时将livinshRNA质粒和ADM转入骨肉瘤细胞,观察其对骨肉瘤的抑制效应。方法:制备了纳米基因载体并进行了表征,用紫外光谱、核磁共振和红外光谱分析测定了这些纳米颗粒的组合物,倒置荧光显微镜和流式细胞术证实了转染效率。应用MTT法检测了ADM和livin基因介导的协同作用,及其纳米颗粒对骨肉瘤细胞的抑制作用。结果:紫外光谱和核磁共振显示纳米载体出现ADM的特征峰,ADM的载药率为(17.43±0.548)%,该载体能有效地将livin shRNA质粒转入骨肉瘤细胞中。转染后骨肉瘤细胞存活率显著低于游离ADM组和纳米基因载体组(P<0.05)。纳米基因载体组对骨肉瘤细胞的增殖抑制作用显著高于ADM组(P<0.05)。结论:本研究中DEX-ADM-PEI纳米能有效地将ADM和livin shRNA质粒同时转入骨肉瘤细胞中,对骨肉瘤细胞增殖的协同抑制作用显著高于ADM。Objective： To construct gene vector of dextran-adriamycin and transfect livin-shRNA plasmid into osteosarcoma cells,then study the inhibitory effect on osteosarcoma. Methods： The gene vector of dextran-adriamycin was constructed. The composition of these nanoparticles was determined by ultraviolet spectrum analysis,1H nuclear magnetic resonance,and infrared spectroscopic analysis. The transfection efficiency was confirmed by converted fluorescence microscope and flow cytometry. The synergistic effects of adriamycin and livin gene silencing mediated by these nanoparticles on the inhibition of osteosarcoma cells were detected by MTT assays. Results：DEX-ADM-PEI conjugation was synthesized successfully. Compared with pure dextran,noticeable absorption peak was shown at 490 nm in the ultra-violet spectrum,comfirming the existence of ADM moiety in the DEX-ADM-PEI conjugation. In addition,the coupling efficiency of ADM in the DEX-ADM-PEI conjugation was（ 17. 43 ±0. 548） %. The proton peaks of PEI and ADM indicated that PEI and ADM were grafted to the dextran chain. Thesynergistic effects of livin shRNA and Adriamycin on inhibiting the growth of osteosarcoma cells were significantly better than that of sole livin-shRNA or adriamycin（ P〈0. 05）. Conclusion： DEX-ADM-PEI nanoparticles efficiently and selectively deliver both livin shRNA and adriamycin into osteosarcoma cells with low cytotoxicity. These nanoparticles could generate synergistic inhibitory effects on the growth of osteosarcoma cell lines.

关 键 词：葡聚糖 聚乙烯亚胺 骨肉瘤 多柔比星 凋亡抑制蛋白 

分 类 号：R979.1[医药卫生—药品]