Synthesis and characterization of folate-PEG-grafted-hyperbranched-PEI for tumor-targeted gene delivery

A great challenge for gene therapy is to develop a high efficient gene delivery system with low toxicity. Nonviral vectors are still attractive although the current agents displayed some disadvantages (i.e., low transfection efficiency, high toxicity). To overcome the high toxicity of poly(ethylene...

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Bibliographic Details
Published in:Biochemical and biophysical research communications 2008-03, Vol.367 (4), p.874-880
Main Authors: Liang, Bing, He, Ming-Liang, Xiao, Zhong-Peng, Li, Yi, Chan, Chu-yan, Kung, Hsiang-Fu, Shuai, Xin-Tao, Peng, Ying
Format: Article
Language:English
Subjects:
Biocompatible Materials - chemistry
DNA - administration & dosage
DNA - chemistry
DNA - genetics
Drug Carriers - chemistry
FA-PEG-g-hy-PEI
FA-receptor
Folic Acid - chemistry
Gene Targeting - methods
Imines - chemistry
In vitro gene transfer
Materials Testing
Polyethylene Glycols - chemistry
Polyethylenes - chemistry
Transfection - methods
Transfection efficiency
Tumor targeting
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Summary:A great challenge for gene therapy is to develop a high efficient gene delivery system with low toxicity. Nonviral vectors are still attractive although the current agents displayed some disadvantages (i.e., low transfection efficiency, high toxicity). To overcome the high toxicity of poly(ethylene imine) (PEI) and low transfection efficiency of PEGylated PEI (PEG-PEI), we linked a cell specific target molecule folate (FA) on poly(ethylene glycol) (PEG) and then grafted the FA-PEG onto hyperbranched PEI 25 kDa. The FA-PEG- grafted-hyperbranched-PEI (FA-PEG-PEI) effectively condensed plasmid DNA (pDNA) into nanoparticles with positive surface charge under a suitable N/P ratio. Tested in deferent cell lines (i.e., HEK 293T, glioma C6 and hepatoma HepG2 cells), no significant cytotoxicity of FA-PEG-PEI was added to PEG-PEI. More importantly, significant transfection efficiency was exhibited in FA-targeted cells. Reporter assay showed that FA-PEG-PEI/pDNA complexes had significantly higher transgene activity than that of PEI/pDNA in folate-receptor (FR) positive (HEK 293T and C6) cells but not FR-negative (HepG2) cells. These results indicated that FA-PEG-PEI might be a promising candidate for gene delivery with the characteristics of good biocompatibility, potential biodegradability, and relatively high gene transfection efficiency.
ISSN:0006-291X
1090-2104
DOI:10.1016/j.bbrc.2008.01.024