S-Space College of Veterinary Medicine (수의과대학) Dept. of Veterinary Medicine (수의학과) Journal Papers (저널논문_수의학과)
Galactosylation of Chitosan-Graft-Spermine as a Gene Carrier for Hepatocyte Targeting In Vitro and In Vivo
- Kim, Ji-Hye; Kim, You-Kyoung; Arash, Minai-Tehrani; Hong, Seong-Ho; Lee, Jae-Ho; Kang, Bit Na; Bang, Yong-Bin; Cho, Chong-Su; Yu, Dae-Yeul; Jiang, Hu-Lin; Cho, Myung-Haing
- Issue Date
- Journal of Nanoscience and Nanotechnology, Vol.12 No.7, pp.5178-5184
- Gene Therapy; Non-Viral Gene Delivery; Hepatocyte Targeting; Galactosylated Chitosan-Graft-Spermine
- Polyethyleneimine (PEI) has been described as a highly efficient gene carrier due to its efficient proton sponge effect within endosomes. However, many studies have demonstrated that PEI is toxic and associated with a lack of cell specificity despite high transfection efficiency. In order to minimize the toxicity of PEI, we prepared chitosan-graft-spermine (CHI-g-SPE) in a previous study. CHI-g-SPE showed low toxicity and high transfection efficiency. However, this compound also had limited target cell specificity. In the present study, we synthesized galactosylated CHI-g-SPE (GCS) because this modified GCS could be delivered specifically into the liver due to hepatocyte-specific galactose receptors. The DNA-binding properties of GCS at various copolymer/DNA weight ratios were evaluated by a gel retardation assay. The GCS copolymer exhibited significant DNA-binding ability and efficiently protected DNA from nuclease attack. Using energy-filtered transmission electron microscopy (EF-TEM), we observed dense spherical, nano-sized GCS/DNA complexes with a homogenous distribution. Most importantly, GCS was associated with remarkably low cytotoxicity compared to PEI in HepG2, HeLa, and A549 cells. Moreover, GCS carriers specifically delivered the gene-of-interest into hepatocytes in vitro as well as in vivo. Our results suggest that the novel GCS described here is a safe and highly efficient carrier for hepatocyte-targeted gene delivery.
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