中文摘要：

大多数抗肿瘤药物难以穿透血脑屏障（BBB）因而无法用于脑胶质瘤的治疗。葡萄糖转运体（GLUTs）在血脑屏障和脑胶质瘤细胞上均有高度表达,这使得葡萄糖转运体相关配体修饰的药物载体跨越血脑屏障、靶向脑胶质瘤细胞成为可能。本研究之目的在于合成一种新的葡萄糖转运体配体靶向材料TPGS_（1000）-Glu、制备TPGS_（1000）-Glu修饰的表阿霉素脂质体,并评价该脂质体制剂的药物效应。评价方法主要在体外血脑屏障共培养模型和脑胶质瘤细胞上进行。TPGS_（1000）-Glu以TPGS_（1000）-COOH和4-氨基苯基-β-D-吡喃葡萄糖苷（Glu）为原料进行合成。基质辅助激光解析电离飞行时间质谱（MALDI-TOF-MS）验证结果显示,试验成功的合成了TPGS_（1000）-Glu。研制的TPGS_（1000）-Glu修饰表阿霉素脂质体具有包封率高（〉97%）、纳米粒径（90nm）、在含血清缓冲体系中药物泄漏少等理化特征。本研究还建立了血脑屏障与脑胶质瘤共培养模型,在该模型中加入TPGS_（1000）-Glu修饰表阿霉素脂质体后,该脂质体药物表现出明显的跨越血脑屏障效应、并在跨越血脑屏障后表现出较强的脑胶质瘤细胞摄取效应及抗脑胶质瘤效应。因此,合成的TPGS_（1000）-Glu为血脑屏障提供了一种新的靶向配体,而所制备的TPGS_（1000）-Glu修饰表阿霉素脂质体则为脑胶质瘤治疗提供了一种有潜力的抗肿瘤制剂。

英文摘要：

Most of antieancer agents can not be used for treatment of brain glioma due to the existence of the blood brain barrier （BBB）. The over-expression of glucose transporters （GLUTs） on the BBB and brain glioma cells enables the possibility that the GLUTs ligand modified drug carrier transports across the BBB, and targets to the brain glioma cells. The objectives of the present study were to synthesize a new glucose conjugate material, TPGS1000-Glu, develop a kind of TPGSI00o-Glu modified epirubicin liposomes, and evaluate their efficacy. The studies were performed on the BBB co-culture model and brain glioma cells in vitro. TPGS 1000-Glu was synthesized by conjugating TPGSlo00_COOH with 4-aminophenyl-[3-D-glucopyranoside （Glu）, and confirmed by MALDI-TOF-MS spectrum. TPGS~0oo-GIu modified epirubicin liposomes were prepared with a high drug encapsulation efficiency （〉97%）, a nanosize （approximately 90 nm）, and a minimal drug leakage in fetal bovine serum （FBS）-containing buffer system. The BBB co-culture model was established, and after applying TPGSl0oo-Glu modified epirubicin liposomes to the model, transport of liposomal drug across the BBB was evidenced. Besides, TPGS1000-Glu modified epirubicin liposomes showed the strongest cellular drug uptake and anti-glioma efficacy after transport across the BBB in vitro. The synthesized TPGS1000-Glu material could offer a new targeting ligand for the BBB, while the developed TPGS1000-Glu modified epirubicin liposomes might provide a potential anticancer formulation for treatment of brain glioma.