Functional study of dextran-graft-poly((2-dimethyl amino)ethyl methacrylate) gene delivery vector for tumor therapy

Abstract

The obstacle of gene therapy is the shortage of efficient delivery system. The development of the gene delivery system with high transfection efficiency and low toxicity appears to be crucial. Recently, we reported that the dextran-graft-poly((2-dimethyl amino)ethyl methacrylate) (DPD) can be potentially used as efficient gene vector. Herein, DPD was systematically studied for its potential in tumor gene therapy. DPD was synthesized and characterized by agarose gel electrophoresis, particle size and zeta potential. The particle size and zeta potential of the DPD/enhanced green fluorescent protein (pEGFP-C1) plasmid complexes at various N/P ratios were 130-150 nm and about 40 mV, respectively. The results showed that DPD exhibit a higher transfection effect compared with Lipofectamine 2K (Lipo 2K), a commercialized vector. The possibility of DPD in gene therapy was evaluated using p53, a gene that has been wildly applied in the research of cancer gene therapy. DPD/pEGFP-C1-p53 complex was found to be able to inhibit tumor cell proliferation through cell cycle arrest and apoptosis. Moreover, the tumor growth was found to be restrained when DPD/pEGFP-C1-p53 complex was used in a xenograft MCF7 tumor model invivo. These observations indicated that DPD/pEGFP-C1-p53 complex may be considered to be an efficient delivery system for tumor gene therapy.