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Title 

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

Authors 

J H KimY K KimM T ArashS H HongJ H LeeB N KangY B BangC S ChoDae Yeul YuH L JiangM H Cho

Publisher 

American Scientific Publishers

Issue Date 

2012

Citation 

Journal of Nanoscience and Nanotechnology, vol. 12, no. 7, pp. 5178-5184

Keywords 

Galactosylated Chitosan-Graft-SpermineGene TherapyHepatocyte TargetingNon-Viral Gene Delivery

Abstract 

Polyethyleneimine (PEI) has been described as a highly ef?cient gene carrier due to its ef?cient proton sponge effect within endosomes. However, many studies have demonstrated that PEI is toxic and associated with a lack of cell speci?city despite high transfection ef?ciency. 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 ef?ciency. However, this compound also had limited target cell speci?city. In the present study, we synthesized galactosylated CHI-g-SPE (GCS) because this modi?ed GCS could be delivered speci?cally into the liver due to hepatocyte-speci?c 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 signi?cant DNA-binding ability and ef?ciently 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 speci?cally 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 ef?cient carrier for hepatocyte-targeted gene delivery.

ISSN 

1533-4880

Link 

http://dx.doi.org/10.1166/jnn.2012.6376

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2017-04-19


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