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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 1H 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. [ABSTRACT FROM AUTHOR]

Polyethylenimine (PEI) is the polymer most commonly used for transferring plasmids into eukaryotes, but its gene-transfer efficiency is lower compared to viral vectors. Receptors targeting PEI combined with ligands can enhance efficiency of gene transfer into the corresponding receptor-positive cells. Using the double-receptor-mediated pathway of viral infection, in this study we synthesized a novel non-viral vector based on PEI combined with two peptides recognizing FGF receptors (peptide YC25) and integrins (peptide CP9) on the cell surface. The dual targeting vector showed a physicochemical character similar to that of PEI, such as pDNA formation, particle size, zeta potential and lower toxicity. In vitro gene transfer showed that the dual-receptor targeted vector (YC25-PEI-CP9) exhibited a markedly higher transgene efficiency in cell lines with positive expression of FGF receptors and integrins, compared with single-peptide-modified PEI or unmodified PEI. In the cells with only integrin-positive expression, YC25-PEI-CP9 mediated a higher transgene expression than PEI but lower than CP9-PEI. The corresponding free peptides could inhibit the transgene efficiency of the peptide-coupled PEI. In vivo gene transfer in tumor-bearing nude mice also demonstrated that the dual-targeting vectors showed a significantly enhanced transfection efficiency in tumors with positive expression of FGF receptors and integrins. The synthesized polymer YC25-PEI-CP9 has the prospect to act as a novel kind of non-viral vector in gene therapy. [ABSTRACT FROM AUTHOR]