Apoptosis induced by transferring cytosine deaminase suicide gene into kinds of cancer cells with novel polyamidoamine dendrimers / 药学学报

ABSTRACT

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 kDa. The optimum ratio of G5 PD dendrimer complexed with plasmid DNA was 0.21, 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 11 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/pCD-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.