title: Galactosylation of chitosan-graft-spermine as a gene carrier for hepatocyte targeting in vitro and in vivo.
abstract: 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.
authors.affiliation: Department of Nano Science and Techonology, Graduate School of Convergence Science and Technology, Seoul National University, Suwon 443-270, Korea.
authors.forename: Ji-Hye
authors.initials: JH
authors.lastname: Kim
authors.forename: You-Kyoung
authors.initials: YK
authors.lastname: Kim
authors.forename: Minai-Tehrani
authors.initials: MT
authors.lastname: Arash
authors.forename: Seong-Ho
authors.initials: SH
authors.lastname: Hong
authors.forename: Jae-Ho
authors.initials: JH
authors.lastname: Lee
authors.forename: Bit Na
authors.initials: BN
authors.lastname: Kang
authors.forename: Yong-Bin
authors.initials: YB
authors.lastname: Bang
authors.forename: Chong-Su
authors.initials: CS
authors.lastname: Cho
authors.forename: Dae-Yeul
authors.initials: DY
authors.lastname: Yu
authors.forename: Hu-Lin
authors.initials: HL
authors.lastname: Jiang
authors.forename: Myung-Haing
authors.initials: MH
authors.lastname: Cho
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D048271:Chitosan / Q000737:chemistry*; D004247:DNA / Q000008:administration & dosage / Q000493:pharmacokinetics*; D004337:Drug Carriers / Q000138:chemical synthesis; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000378:metabolism*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D053769:Nanocapsules / Q000737:chemistry*; D013096:Spermine / Q000737:chemistry*; D014162:Transfection / Q000379:methods*
chemical_list: D004337:Drug Carriers; D053769:Nanocapsules; D013096:Spermine; D004247:DNA; D048271:Chitosan