title: A dual-functionally modified chitosan derivative for efficient liver-targeted gene delivery.
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, (1) H 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.
authors.affiliation: Advanced Biomaterials and Tissue Engineering Center, Huazhong University of Science and Technology, Wuhan 430074, People's Republic of China.
authors.forename: Bo
authors.initials: B
authors.lastname: Xiao
authors.forename: Xiaoyu
authors.initials: X
authors.lastname: Wang
authors.forename: Zhiye
authors.initials: Z
authors.lastname: Qiu
authors.forename: Jun
authors.initials: J
authors.lastname: Ma
authors.forename: Lei
authors.initials: L
authors.lastname: Zhou
authors.forename: Ying
authors.initials: Y
authors.lastname: Wan
authors.forename: Shengmin
authors.initials: S
authors.lastname: Zhang
mesh_terms: D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D048271:Chitosan / Q000031:analogs & derivatives* / Q000737:chemistry* / Q000378:metabolism; D003460:Crystallization; D004247:DNA / Q000008:administration & dosage / Q000235:genetics; D004587:Electrophoresis, Agar Gel; D018390:Gene Targeting / Q000379:methods*; D018014:Gene Transfer Techniques / Q000295:instrumentation*; D006367:HeLa Cells; D006801:Humans; D007202:Indicators and Reagents; D008099:Liver / Q000502:physiology*; D009682:Magnetic Resonance Spectroscopy; D010316:Particle Size; D017550:Spectroscopy, Fourier Transform Infrared; D014162:Transfection; D014961:X-Ray Diffraction
chemical_list: D007202:Indicators and Reagents; D004247:DNA; D048271:Chitosan