摘要
为合成一种能携带目的基因并靶向富集到肝组织中的有效载体,用还原胺化法将乳糖共价连接于羧甲基壳聚糖。成分分析表明制备出的乳糖化羧甲基壳聚糖共价结合物中乳糖与羧甲基壳聚糖的摩尔比为15:1。采用真核细胞表达载体β-半乳糖苷酶报道基因,分别观察了其在体内和体外对肝细胞的定向释放及对基因表达的影响。结果表明,DNA与Lac-CMCS的最佳质量比是1:12。体内实验证实DNA与Lac-CMCS形成复合物后能在肝组织中富集并在肝细胞中有效表达。合成的乳糖化羧甲基壳聚糖具备肝靶向导向能力,是一种有效的肝靶向载体。
To synthesize a delivery cartier targeting the designed DNA into the parenchymal liver cells, the lactose was coupled to carboxymethylchitosan by reductive amination with NaBH3CN. In vitro Eukaryotic expression reporter gene β-galactosidase was used to analyse the target delivery ability and the gene expression of the Lac-CMCS in cell culture and in mice. The analyses results of structure and composition showed that the Lac-CMCS was synthesized and its Molar ratio of lactose to CMCS was 15：1. Composite proportion of complexes can also influence the effect of delivery,and the best composite proportion of DNA to Lac-CMCS is 1 ： 12. The coupled reporter gene could be accumulated in the liver and expressed in the parenchymal liver cells. So the Lac-CMCS is an efficient delivery cartier for targeting DNA to parenchymal liver cells.
出处
《天然产物研究与开发》
CAS
CSCD
2005年第5期600-602,631,共4页
Natural Product Research and Development
关键词
乳糖化羧甲基壳聚糖
合成
肝细胞
基因表达
lactosaminated carboxymethylchitosan
synthesis
parenchymal liver cells
gene expression
