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Synthesis and characterization of folate-poly(ethylene glycol) chitosan graft-polyethylenimine as a non-viral carrier for tumor-targeted gene delivery
The use of chitosan and chitosan derivatives for gene delivery is limited due to the low transfection efficiency and difficulty in transfecting into a variety of cell types, including some cancer cells overexpressing folate receptor (FRs). In order to solve this problem, folate (FA) and poly(ethylen...
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Published in: | African journal of biotechnology 2011-07, Vol.10 (32), p.6120-6129 |
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Main Authors: | , , , , , , , |
Format: | Article |
Language: | English |
Online Access: | Get full text |
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Summary: | The use of chitosan and chitosan derivatives for gene delivery is limited due to the low transfection efficiency and difficulty in transfecting into a variety of cell types, including some cancer cells overexpressing folate receptor (FRs). In order to solve this problem, folate (FA) and poly(ethylene glycol) (PEG) was conjugated to chitosan-graft-polyethylenimine (CHI-g-PEI) to enhance water-solubility and the transfection efficiency. In the present study, a cell specific targeting molecule FA was linked on PEG and then grafted the FA-PEG onto CHI-g-PEI. The FA-PEG-grafted CHI-g-PEI (FA-PEG-CHI-g-PEI) effectively condensed the plasmid DNA (pDNA) into nanoparticles with positive surface charge under the suitable nitrogen/phosphorus (N/P) ratio. In vitro, transfection efficiency of the FA-PEG-CHI-g-PEI /pDNA complex in 293T cells and LoVo cells (FRs over-expressing cell lines) increased with increasing N/P ratio under N/P = 15 and was more than 50%, but no significant difference in human lung carcinoma cells (A549) cells (FRs deficient cell lines). Importantly, in vivo luciferase expression showed that the efficiency of FA-PEG-CHI-g-PEI -mediated transfection (50 mu g luciferase plasmid (pLuc), N/P ratio = 15) was comparable to that of adenovirus-mediated luciferase transduction (1 x 10 super(9) pfu) in melanoma-bearing mice. It was concluded that FA-PEG-CHI-g-PEI, which has improved transfection efficiency and FRs specificity in vitro and in vivo, may be useful in gene therapy. |
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ISSN: | 1684-5315 1684-5315 |