Galactosylation of chitosan-graft-spermine as a gene carrier for hepatocyte targeting in vitro and in vivo

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Galactosylation of chitosan-graft-spermine as a gene carrier for hepatocyte targeting in vitro and in vivo
J H Kim; Y K Kim; M T Arash; S H Hong; J H Lee; B N Kang; Y B Bang; C S Cho; Dae Yeul Yu; H L Jiang; M H Cho
Bibliographic Citation
Journal of Nanoscience and Nanotechnology, vol. 12, no. 7, pp. 5178-5184
Publication Year
Polyethyleneimine (PEI) has been described as a highly efcient gene carrier due to its efcient proton sponge effect within endosomes. However, many studies have demonstrated that PEI is toxic and associated with a lack of cell specicity despite high transfection efciency. 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 efciency. However, this compound also had limited target cell specicity. In the present study, we synthesized galactosylated CHI-g-SPE (GCS) because this modied GCS could be delivered specically into the liver due to hepatocyte-specic 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 signicant DNA-binding ability and efciently protected DNA from nuclease attack. Using energy-ltered 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 specically 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 efcient carrier for hepatocyte-targeted gene delivery.
Galactosylated Chitosan-Graft-SpermineGene TherapyHepatocyte TargetingNon-Viral Gene Delivery
Amer Scientific Publishers
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