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穿膜肽TAT和脑肿瘤靶向肽T7双修饰脂质体的制备和体外靶向性评价

发布时间:2018-01-19 06:05

  本文关键词: 脂质体 穿膜肽 血脑屏障 脑肿瘤 出处:《药学学报》2015年01期  论文类型:期刊论文


【摘要】:本文旨在制备T7肽和穿膜肽TAT双修饰的脂质体(T7 and TAT dual modified liposomes,T7-TAT-LIP)用于血脑屏障和脑肿瘤细胞双级靶向药物递送。研究以CFPE为荧光探针,T7修饰的PEG-DSPE、TAT修饰的PEG-DSPE、卵磷脂、PEG-DSPE和胆固醇为材料,采用成膜水化法制备脂质体,对T7浓度、TAT浓度、连接T7和TAT的PEG长度进行优化,表征其粒径、zeta电位、形态和稳定性。以b End.3细胞和C6细胞为模型,考察T7-TAT-LIP的细胞摄取能力,表征其穿过血脑屏障和脑肿瘤细胞靶向能力。结果表明,T7用量为脂质的6%、修饰T7所用PEG链长为2000、TAT用量为脂质的0.5%、修饰TAT所用PEG链长为1000时所得到的双修饰脂质体被C6细胞摄取能力最强。优化后T7-TAT-LIP粒径为118 nm,zeta电位为-6.32 m V,透射电镜下形态圆整。脂质体在PBS中较为稳定,37℃放置24 h,浊度和粒径无明显变化;4~8℃放置1个月,粒径和PDI无明显变化。在不同时间点,b End.3和C6细胞摄取T7-TAT-LIP的强度均高于单配体修饰脂质体,且随着孵育时间提高,摄取浓度逐渐提高。这些结果说明,双修饰脂质体具有血脑屏障和脑肿瘤细胞双级靶向能力,且效果优于单配体修饰脂质体。
[Abstract]:The aim of this study was to prepare T7 and TAT dual modified liposomes (T7 and dual modified liposomes) modified by T7 peptide and transmembrane peptide TAT. T7-TAT-LIPs were used for the delivery of dual-level targeted drugs in blood-brain barrier and brain tumor cells. The PEG-DSPE modified with CFPE as fluorescence probe was studied. TAT modified PEG-DSPE, phosphatidylcholine PEG-DSPE and cholesterol were used to prepare liposomes by membrane hydration. The length of PEG connecting T7 and TAT was optimized to characterize the particle size, morphology and stability of T7 and TAT. The model was b End.3 cells and C6 cells. The cell uptake ability of T7-TAT-LIP was investigated, and the targeting ability of T7-TAT-LIP through the blood-brain barrier and brain tumor cells was characterized. The results showed that the dosage of T7-TAT-LIP was 6% of lipid. The PEG chain length of modified T7 was 0.5% of that of lipid. When the PEG chain length of modified TAT was 1000, the double modified liposomes were the most capable of uptake by C6 cells. The optimized T7-TAT-LIP particle size was 118nm. The zeta potential was -6.32 MV, and the morphology of liposomes was round under transmission electron microscope. The turbidity and particle size of liposomes remained stable at 37 鈩,

本文编号:1442931

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