中文摘要：

将羧基化的水溶性葡聚糖（Dex）与紫杉醇（PTX）化学偶联,制得载药纳米胶束M（PTX）,再将M（PTX）与嗜神经性病毒衍生肽（RVG29）化学偶联,得到RVG29靶向的载药纳米胶束M（RVG,PTX）.采用核磁共振氢谱（1H NMR）测定了Dex-PTX及RVG-Dex-PTX键合物的分子量,并对2种胶束进行了表征,考察了2种胶束对肿瘤细胞的抑制效果及细胞凋亡情况,观察了C6细胞对荧光标记M（RVG,PTX）和M（PTX）的摄取情况.结果表明,羧基化葡聚糖-紫杉醇键合物的分子量约为16500,紫杉醇的质量约为葡聚糖的20%,RVG29的质量约为葡聚糖的10%.2种胶束的粒径在45～60 nm之间;M（RVG,PTX）胶束对C6细胞的抑制作用具有浓度和时间依赖性,细胞抑制率随着作用时间和药物浓度增加而增加,且M（RVG,PTX）胶束对C6细胞的抑制作用强于M（PTX）胶束.细胞摄取实验结果表明,与M（PTX）相比,C6细胞摄取了更多的M（RVG,PTX）胶束.如果先用游离的RVG29处理C6细胞,再进行细胞实验,则M（RVG,PTX）胶束对C6细胞生长的抑制作用及被C6细胞摄取的比率显著降低,与M（PTX）相当.表明靶向载药胶束M（RVG,PTX）中的RVG29保留了游离RVG29的活性,对C6细胞依然具有靶向效应,从而介导了M（RVG,PTX）被C6细胞的摄取,增强了对C6细胞的生长抑制作用.由于M（RVG,PTX）胶束只使用水溶性葡聚糖作载体,不涉及疏水高分子链段,不需要分别制备载药高分子和靶向高分子然后再共组装,因而制备过程比较简单,同时具有载药和靶向功能.

英文摘要：

Starting with water soluble dextran（ Dex）,paclitaxel（ PTX）-carrying micelles M（ PTX） and Rabies-virus-derived peptide（ RVG29）-targeted and PTX-carrying micelles M（ RVG,PTX） were prepared,by carboxylation of dextran and subsequently by conjugating PTX and RVG29 onto the carboxylated dextran. The products were characterized with nuclear magnetic resonance（1H NMR） spectroscopy,transmission electron microscopy（ TEM）,and dynamic light scattering（ DLS）. The uptakes of the micelles by C6 cells and the inhibition rates of C6 cell growth by the micelles were measured by 3-（ 4,5-dimethyl-2-thiazolyl）-2,5-diphenyl-2-H-tetrazolium bromide（ MTT） assay,by confocal laser scanning microscopy（ CLSM）,and by flow cytometry（ FCM）. The results showed that molecular weight of Dex-PTX was about 16500 and that of RVG-Dex-PTX was about 19800. Micelles M（ PTX） and M（ RVG,PTX） assumed a shape of spheres with a diameter of 45—60 nm. The mass ratio of Dex,PTX and RVG29 was about 100 ∶ 20 ∶ 10. M（ RVG,PTX） exhibited higher cell growth inhibition rate against C6 cells than M（ PTX） and C6 cells took in more M（ RVG,PTX） than M（ PTX） under the same experimental conditions. When C6 cells were treated with free RVG29 prior to cellular experiments,the inhibition rate against C6 cells and the uptake by C6 cells of M（ RVG,PTX） were significantly decreased and came to a level of M（ PTX）. This implied that the enhanced inhibition of C6 cell growth by M（ RVG,PTX） and the enhanced uptake of M（ RVG,PTX） by C6 cells were mediated by RVG29,and the RVG29 species after conjugation with Dex reserved the targeting ability of RVG29 itself to a reasonable extent.Furthermore,in the preparation of M（ RVG,PTX） micelles,only Dex was used as a carrier polymer,no hydrophobic polymer segments were involvd and there was no need of preparing drug-carrying copolymers and targeting copolymers,separately,and then doing co-assembling of them. In short,the manufacturing of M（ RVG