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A dual-functionally modified chitosan derivative for efficient liver-targeted gene delivery

Authors

  • Bo Xiao,

    1. Advanced Biomaterials and Tissue Engineering Center, Huazhong University of Science and Technology, Wuhan 430074, People's Republic of China
    2. Department of Biology, Center for Diagnostics and Therapeutics, Georgia State University, Atlanta, Georgia 30302
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  • Xiaoyu Wang,

    1. Advanced Biomaterials and Tissue Engineering Center, Huazhong University of Science and Technology, Wuhan 430074, People's Republic of China
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  • Zhiye Qiu,

    1. Advanced Biomaterials and Tissue Engineering Center, Huazhong University of Science and Technology, Wuhan 430074, People's Republic of China
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  • Jun Ma,

    1. Advanced Biomaterials and Tissue Engineering Center, Huazhong University of Science and Technology, Wuhan 430074, People's Republic of China
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  • Lei Zhou,

    1. Advanced Biomaterials and Tissue Engineering Center, Huazhong University of Science and Technology, Wuhan 430074, People's Republic of China
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  • Ying Wan,

    Corresponding author
    1. College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, People's Republic of China
    • College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, People's Republic of China
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  • Shengmin Zhang

    Corresponding author
    1. Advanced Biomaterials and Tissue Engineering Center, Huazhong University of Science and Technology, Wuhan 430074, People's Republic of China
    • Advanced Biomaterials and Tissue Engineering Center, Huazhong University of Science and Technology, Wuhan 430074, People's Republic of China
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  • How to cite this article: Xiao B, Wang X, Qiu Z, Ma J, Zhou L, Wan Y, Zhang S. 2013. A dual-functionally modified chitosan derivative for efficient liver-targeted gene delivery. J Biomed Mater Res Part A 2013:101A:1888–1897.

Abstract

Galactosylated chitosan-hydroxypropyltrimethylammonium (gal-HTCC) was synthesized by galactosylating and quaternizing chitosan to endue chitosan with targeting specificity for potential applications as gene vectors. The composition and physicochemical properties of gal-HTCC were characterized by FT-IR, 1H NMR, elemental analysis, X-ray diffraction, and turbidity measurement. It was found that water-soluble gal-HTCC showed a more amorphous structure than chitosan, and it also had a much better plasmid condensation capability than galactosylated chitosan. Cytotoxicity measurements revealed that gal-HTCC showed significantly lower cytotoxicity in HepG2 and HeLa cell lines compared to branched polyethylenimine (bPEI, 25 kDa) which was used as a positive control. The nanoparticles (NPs) consisted of gal-HTCC and plasmid DNA had desirable particle size (around 250 nm) with a narrow size distribution. Confocal laser scanning microscopy confirmed that NPs could be internalized and transported to the nucleus efficiently within 6 h. In vitro gene transfection results indicated that gal-HTCC had significantly higher transfection efficiency (7- to 32-fold) compared to chitosan and gal-chitosan for targetable delivery of pGL3 luciferase plasmid to HepG2, and its transfection efficiency was highly inhibited in the presence of galactose (20 mM). All these results suggest that gal-HTCC can function as a promising nonviral gene vector for efficient liver-targeted gene delivery. © 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2013.

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