Galactosylated liposomes as oligodeoxynucleotides carrier for hepatocyte-selective targeting
Galactosylated liposomes as oligodeoxynucleotides carrier for hepatocyte-selective targeting
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DOI：
10.1691/ph.2007.7.6232
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发表时间：
2007-07-01
期刊：
影响因子：
1.6
通讯作者：
Wang, Siling
中科院分区：
文献类型：
--
作者：
Yu, Fengbo;Jiang, Tongying;Wang, Siling
选择能抑制Survivin基因表达的18聚脱氧核苷酸(ODN)作为模型基因药物。通过1，5-内酯(LA)的内酯与2-(胆甾氧甲酰氨基)乙胺(CHE)的氨基反应，合成了针对表达半乳糖受体的细胞的特异性糖脂(5-胆烷-3-β-基)-1-[2-(乳生物酰胺基)乙基酰胺]甲酸酯(CHE-LA)。以SPC、胆固醇、ChE-LA和寡聚脱氧核苷酸为原料，采用薄膜水合法制备了含ChE-LA寡聚脱氧核苷酸的半乳糖化脂质体。以高氯酸盐(1，1‘-Dioctadecyl-3，3，3’，3‘tetramethylindocarbocyanine perlorate，DIL)作为脂质体制剂的标志物。与常规脂质体(CL)相比，半乳糖基化脂质体(GL)在体内肝组织中的分布显著增加，并且含有寡核苷酸(GLO)的半乳糖基化脂质体在体外也比含有寡脱氧核苷酸(CLO)的常规脂质体更有效地诱导HepG2细胞的凋亡。此外，GLO代表了ODN包封率的提高。
18mer oligodeoxynucleotides (ODNs) which can inhibit survivin gene expression were selected as a model gene drug. The glycolipid (5-cholestan-3 beta-yl)-1-[2-(lactobionyl amido) ethylamido] formate, (CHE-LA) which specific target to the cells expressing galactose receptors was synthesized through the reaction of lactone of lactobiono-1,5-lactone (LA) and the amino-group of 2-(cholesteryloxycarbonylamino) ethylamine (CHE). The galactosylated liposome incorporated with CHE-LA containing oligodeoxynucleotides was prepared with SPC, cholesterol, CHE-LA and oligodeoxynucleotides by the thin-film hydration method. 1,1'-Dioctadecyl-3,3,3',3'tetramethylindocarbocyanine perchlorate (Dil) was used as a marker for all the liposome preparations. Compared with conventional liposomes (CL), the galactosylated liposomes (GL) exhibited a drastically increased distribution to the liver in vivo and the galactosylated liposomes containing oligodeoxynucleotides (GLO) can also more efficiently induced an apoptosis of HepG2 cells in vitro than the conventional liposome containing oligodeoxynucleotides (CLO). In addition, the GLO represented an improving of the ODNs entrapment efficiency.