中文摘要：

本研究证明了一种以季戊四醇衍生物为核的新型聚酰胺-胺型树状大分子（G5 PD dendrimer）可以有效介导融合胞嘧啶脱氨酶（cytosine deamniase,CD）自杀基因在多种肿瘤细胞内表达并诱导其发生凋亡。通过研究G5 PD dendrimer与融合基因形成复合物的性质,筛选出最优处方对肿瘤细胞进行转染,并观察自杀基因促肿瘤细胞凋亡的作用。结果显示,G5 PD dendrimer和质粒的最佳复合比为0.2∶1,复合物的粒径为（100±5）nm。实验中,以G5 PD dendrimer和质粒按质量比1∶1形成的复合物分别对3种肿瘤细胞进行转染,其效果均高于商用转染试剂。抑制肿瘤细胞增殖实验发现转染了CD基因的细胞可以在很短的时间内将少量5-氟胞嘧啶（5-FC）高效地转化为氟尿嘧啶（5-FU）并抑制癌细胞增殖,而且该结果也呈现出一定的细胞选择性。上述结果表明,该类新型的CD/5-FC自杀基因传递系统具有较好的应用前景。

英文摘要：

This study demonstrates efficacy of a novel polyamidoamine dendrimers（PAMAM dendrimers） with pentaerythritol derivatives as the core（G5 PD dendrimer） in deliver of the cytosine deaminase（CD） gene and EGFP gene fusion plasmid into different tumor cell lines to induce apoptosis. The physical and chemical properties of G5 PD dendrimers in terms of DNA complexation, particulate properties and transfection efficiencies were investigated and compared with commercial gene vectors PEI 25 k Da. The optimum ratio of G5 PD dendrimer complexed with plasmid DNA was 0.2∶1, and the particle size of the complex was（100 ± 5） nm. Compared with the commercial gene carriers PEI, G5 PD dendrimer exhibited a higher transfection efficiency at the weight ratio of 1∶1 in three different cell lines, given the fact that PEI are different from PAMAM dendrimers in terms of molecular structure. Furthermore, the cytotoxicity assays of the cell lines transfected with G5 PD dendrimer/p CD-EGFP-N1 followed by exposure to various concentrations of 5-fluorocytosine（5-FC） also showed that the transfected cell lines could generate a very low amount of 5-FC to 5-fluorouracil（5-FU） in a short period of time, which indicating the high expression level of CD gene in the cell line. These results indicate that the CD/5FC system of G5 PD dendrimer has an excellent efficacy in gene delivery.