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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。
This study demonstrated that a novel polyamide-amine dendrimer with pentaerythritol derivatives as nucleus can effectively mediate the fusion of cytosine deamniase (CD) suicide gene in many kinds of tumors Intracellular expression and induction of apoptosis. By studying the properties of G5 PD dendrimer and the fusion gene, the optimal prescriptions were screened for transfection of tumor cells, and the effect of suicide gene on the apoptosis of tumor cells was observed. The results showed that the best composite ratio of Gd PD dendrimer and plasmid was 0.2:1, and the particle size of the complex was (100 ± 5) nm. In the experiment, three kinds of tumor cells were transfected with the complex of G5 PD dendrimer and plasmid at a mass ratio of 1: 1, respectively, and the effect was higher than that of commercial transfection reagent. Inhibition of Tumor Cell Proliferation It was found that cells transfected with the CD gene efficiently converted small amounts of 5-fluorocytosine (5-FC) to fluorouracil (5-FU) and inhibited cancer cell proliferation in a short period of time, The results also showed a certain degree of cell selectivity. The above results show that this new type of CD / 5-FC suicide gene delivery system has a good prospect.