The construction of a novel kind of non-viral gene delivery vector based on protein as core backbone

被引:2
作者
Li, D. [2 ]
Kong, Y. [1 ]
Yu, H. [3 ]
Lehtinen, A. [4 ]
Huang, H. [3 ]
Shen, F. [3 ]
Min, L. [1 ]
Zhou, J. [1 ]
Tang, G. [1 ]
Wang, Q. [3 ]
机构
[1] Zhejiang Univ, Inst Chem Biol & Pharmaceut Chem, Hangzhou 310028, Peoples R China
[2] Zhejiang Univ, Sir Run Run Shaw Hosp, Sch Med, Dept Oncol, Hangzhou 310003, Peoples R China
[3] Zhejiang Univ, Inst Immunol, Hangzhou 310031, Peoples R China
[4] Helsinki Univ Technol, Dept Chem Technol, FIN-02015 Helsinki, Finland
关键词
gene delivery; polyethylenimine; transferring; vector;
D O I
10.1111/j.1423-0410.2007.01025.x
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Background and Objectives A novel kind of non-viral gene delivery vector based on transferrin (Tf) as the core component was constructed with high transfection efficiency and low toxicity. Materials and Methods The synthesis vector of Tf-PEI600 was confirmed by different physicochemical methods, including H-1 nuclear magnetic resonance, gel permeation chromatography, X-ray and thermogravimetric analysis. The cytotoxicity and gene delivery efficiency of the synthesized vector were verified by in vitro experiments. Results The agarose gel electrophoresis assay indicated that the novel copolymer Tf-PEI600 could efficiently condense plasmid DNA and the condensed nanoparticles exhibited a spherical shape. As the weight ratio of Tf-PEI600 to DNA reached 15.0, the particle size (about 200 nm) and the zeta potential (about 20 mV) of the nanoparticles became optimal for gene delivery. The methylthiazolyl tetrazolium (MTT) assay showed the cytotoxicity of Tf-PEI600 to be similar to that of PEI600 and much lower than that of PEI25kDa. In gene-delivery experiments with COS-7 cells and HepG2 cells, the Tf-PEI600 showed about a 30- to 53-fold higher efficiency than PEI600 and nearly equal to that of PEI25kDa. Conclusions These data suggest that Tf-PEI600, with the advantages of low toxicity and high gene-delivery efficiency, might have great prospects in the practice of gene delivery. The core-shell structure of Tf-PEI600 also provided a novel strategy for the construction of non-viral gene delivery vectors.
引用
收藏
页码:234 / 241
页数:8
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