肿瘤靶向性聚酰胺-胺型树枝状高分子基因载体的合成及性能研究

摘要

In an attempt to investigate the effect of transferrin conjugation on the transfec-tion ability of the G5 PD PAMAM/DNA complexes, a tumor-targeted gene carriers, indicated as G5 PD PAMAM-Tf was synthesized by conjugating transferrin via reversible disulfide linkage on PAMAM surface. The important parameters for the physico-chemical properties of this delivery system were investigated and the transfection efficiencies of G5 PD PAMAM-Tf were also evaluated in different cell lines. The results showed that transferrin modification could enhance the delivery of pEGFP-C1 into tumor cells MCF-7 and HepG2. Meanwhile, the addition of free transferrin could significantly decrease the transfection efficiencies of G5 PD PAMAM-Tf in tumor cells, which indicated that the cellular uptake of such vectors is mainly based on transferrin receptor-mediated endocytosis.%通过二硫键可逆地将转铁蛋白偶联在以季戊四醇衍生物为核的第5代聚酰胺-胺型树枝状大分子(G5 PD PAMAM)载体表面上,合成出肿瘤靶向性基因载体G5 PD PAMAM-dsTf.系统研究了该载体介导绿色荧光蛋白质粒pEFGP-C1转染不同细胞的性能.结果表明,相比于G5 PD PAMAM对癌细胞MCF-7和HepG2的转染效率,G5 PD PAMAM-dsTf的转染性能均有不同程度的提高,显示出较好的肿瘤靶向性.同时,游离转铁蛋白的拮抗实验也证明了G5 PD PAMAM-dsTf可以通过癌细胞表面的转铁蛋白受体TFR介导进入细胞.