键合靶向纳米胶束对脑胶质瘤细胞的组织相容性和靶向性

Biocompatibility and brain-targeting ability of nanomicelles on glioma cells

目的:探讨转铁蛋白受体的单克隆抗体(OX26)与聚乳酸聚乙二醇(PEG-PLA)键合靶向纳米胶束(copolymer/OX26)的生物相容性和安全性,阐明其作为脑胶质瘤靶向治疗载体的可行性。方法:体外培养C6胶质瘤细胞,用不同浓度(10.0、20.0、40.0和80.0mg·L-1)纳米胶束作为实验组,不含胶束的培养液作为对照组;台盼蓝染色法检测靶向纳米胶束对胶质瘤C6细胞的增殖抑制作用;流式细胞术检测靶向纳米胶束作用后C6胶质瘤细胞凋亡和细胞周期变化;激光共聚焦显微镜观察肿瘤细胞对靶向胶束的摄入情况。结果:与对照组比较,OX26靶向纳米胶束作用后C6细胞数无明显改变(P>0.05),各组细胞凋亡率和细胞周期细胞比例差异亦无统计学意义(P>0.05);靶向纳米胶束组细胞内的荧光强度明显高于空白胶束组和空白对照组(P<0.05),并且这种作用随药物作用时间和浓度的增加而增加。结论:OX26靶向纳米胶束对C6细胞增殖和凋亡无影响,键合OX26提高了C6细胞对胶束的摄入量。

Objective To investigate the biocompatibility and safety of nanoscale brain-targeting-carrier micelles＆amp;nbsp;[poly （ethylene）-b-poly （lactic acid）/OX26 conjugate micells （copolymer/OX26）],and to explore its possibility as brain-targeted-drug carrier for brain glioma.Methods The C6 glioma cells were cultured in vitro and divided into experimental groups with different concentrations （10, 20, 40, 80 mg · L-1 ）of nano micelle, and the medium without micelle was used as control group.The inhibitory effect of nano-micelles on the rat brain glioma C6 cells was examined by Trypan blue cell counting assay.Flow cytometry （FCM）was used to detect the changes of apoptosis and cell cycle of C6 cells,and confocal laser scanning microscope （CLSM）was performed to analyze the distribution of copolymer/OX26 into C6 cells. Results The results of Trypan blue cell counting assay showed copolymer/OX26 didn’t affect the growth of C6 cells,and there were no significant differences in the number of C6 cells between control group and expreimental groups （P 〉0.05）.The results of FCM showed that the cell cycle and and the apoptotic rates of C6 cells had no changes compared with control group （P 〉 0.05）.The results of CLSM showed that the fluorescence intensities in experimental groups were higher than those in blank micelles group and blank control group （P 〈 0.05 ）, and they were increased in dose- and time-dependent manner （P 〈0.05）.Conclusion Copolymer/OX26 has no effect on the growth and apoptosis of glioma cells.By bonding OX26,copolymer/OX26 can significantly increase the intake of C6 cells on the nano micelles.