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目的对比研究胆固醇上以酯键、醚键的不同连接方式修饰穿膜肽TAT(源于Tat蛋白碱性结构域的短肽)脂质体的体内外特性。方法以Rho-PE为荧光标记物,制备在胆固醇上以酯键、醚键的不同连接方式修饰穿膜肽TAT的脂质体,用激发光散射粒度仪测定其粒径;在小鼠血清中考察两种衍生物材料72 h稳定性;以HUVEC、C6、C26细胞为受试细胞,对标记Rho-PE的两种脂质体进行细胞摄取的定量分析;以DID为荧光标记物,以荷瘤小鼠(C26)为受试动物,考察肿瘤部位定量摄取。结果以酯键、醚键不同连接方式的胆固醇上修饰/未修饰有穿膜肽TAT的脂质体的粒径分别为114.50±12.31、113.80±6.74、103.10±1.91、105.10±2.06 nm;多分散系数(PDI)分别为0.227±0.029、0.207±0.039、0.203±0.009、0.216±0.016;小鼠血清中以醚键连接的胆固醇衍生物材料具有良好的稳定性。胆固醇上以不同连接方式修饰的TAT脂质体中,以醚键连接方式制备的脂质体的体外细胞摄取以及体内肿瘤摄取均优于酯键连接方式制备的脂质体。结论醚键修饰的胆固醇衍生物材料所制备的连接TAT的脂质体相较于酯键连接者,有较好的体内外摄取效果。
OBJECTIVE: To compare the in vivo and in vitro characteristics of liposomes with transmembrane peptide TAT (short peptide derived from the basic domain of Tat protein) modified by different linkages of cholesterol ester and ester bond. Methods Rho-PE was used as a fluorescent marker to prepare liposomes with different attachment of ester and ether linkages, and the particle size of TAT was modified by using excitation light scattering particle size analyzer. In mouse serum The stability of the two derivatives was investigated for 72 h. The cellular uptake of Rho-PE was quantified using HUVEC, C6 and C26 cells as the test cells. Using DID as fluorescent marker, Tumor mice (C26) were tested animals and examined for quantitative ingestion of tumor sites. Results The liposomes with and without TTV modified by ester linkages and ether linkages were 114.50 ± 12.31, 113.80 ± 6.74, 103.10 ± 1.91 and 105. ± 2.06 nm, respectively. The polydispersity (PDI) were 0.227 ± 0.029, 0.207 ± 0.039, 0.203 ± 0.009 and 0.216 ± 0.016, respectively. The ether bond-linked cholesterol derivatives in mouse serum had good stability. In TAT liposomes modified with different linkages in cholesterol, liposomes prepared by ether linkage were better in in vitro cellular uptake and in vivo tumor uptake than liposomes prepared by ester bond. Conclusion The TAT-linked liposomes prepared by the ether bond-modified cholesterol derivatives have better in vivo and in vitro uptake than the ester-linked ones.