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目的制备用于治疗脑部肿瘤的多功能靶向性表柔比星脂质体、对其进行理化表征并考察其对脑毛细血管内皮细胞的靶向性和对脑胶质瘤细胞的抑制效应。方法以葡萄糖类似物2-氨基-2-脱氧-β-D-吡喃葡萄糖(NH2-Glu)为靶向分子,通过与长循环胆固醇材料进行化学合成,制备针对血脑屏障毛细血管内皮细胞和脑胶质瘤细胞葡萄糖转运体的靶向性功能材料;将此靶向材料修饰到脂质体上,以表柔比星为抗癌药,制备多功能靶向性表柔比星脂质体;对该脂质体进行理化表征;在脑毛细血管内皮细胞和脑胶质瘤细胞上考察其摄取情况;在脑胶质瘤细胞上考察其抑制效应。结果由飞行时间质谱分析证实,成功制备了聚乙二醇琥珀酰亚胺酯-胆固醇(Chol-PEG2000-Glu)靶向性材料。构建的多功能靶向性表柔比星脂质体经粒径仪和原子力显微镜测定粒径均一,约125 nm,电位测量呈负电性。表柔比星的包封率约为93%。流式细胞仪测定结果显示,相对于表柔比星脂质体对照制剂,多功能靶向性表柔比星脂质体在脑毛细血管内皮细胞和2种脑胶质瘤细胞中摄取强度均显著提升。在体外细胞毒实验中,多功能靶向性表柔比星脂质体对脑胶质瘤细胞抑制效果明显增强。结论本实验合成了一种新的靶向性长循环胆固醇材料并成功构建了多功能靶向性表柔比星脂质体,该载药脂质体可被脑毛细血管内皮细胞摄取、表现出跨越血脑屏障潜能并可靶向性抑制脑胶质瘤细胞生长。
OBJECTIVE: To prepare multifunctional targeting epirubicin liposomes for the treatment of brain tumors, to investigate its physical and chemical characterization and to investigate its targeting of brain capillary endothelial cells and its inhibitory effect on glioma cells . Methods The glucose analogs 2-amino-2-deoxy-β-D-glucopyranoside (NH2-Glu) was used as a target molecule to synthesize peptides targeting blood-brain barrier capillary endothelial cells and Targeting glioma cell glucose transporter functional material; this targeting material modified to liposomes, epirubicin anticancer drug, preparation of multi-purpose targeting epirubicin liposomes The liposomes were identified by physical and chemical methods. The uptake of the liposomes was evaluated on brain capillary endothelial cells and glioma cells. The inhibitory effect was also observed on glioma cells. The results confirmed by time of flight mass spectrometry confirmed the successful preparation of polyethylene glycol succinimidyl ester-cholesterol (Chol-PEG2000-Glu) targeting material. The multifunctional targeting epirubicin liposomes were characterized by particle size analyzer and atomic force microscopy. The particle size was about 125 nm and the potential was negative. Epirubicin encapsulation efficiency of about 93%. The flow cytometry results showed that the uptake of multifunctional targeting epirubicin liposomes in brain capillary endothelial cells and two glioma cells relative to that of epirubicin liposome control Significantly improved. In vitro cytotoxicity experiments, multi-purpose targeting epirubicin liposomes on glioma cells inhibitory effect was significantly enhanced. CONCLUSIONS: A novel targeted long circulating cholesterol material was synthesized in this experiment and a multifunctional targeting epirubicin liposome was successfully constructed. The drug-loaded liposomes can be taken up by brain capillary endothelial cells and showed Cross the potential of the blood-brain barrier and can target the growth of glioma cells.