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Suppression of tumor growth in H-ras12V liver cancer mice by delivery of programmed cell death protein 4 using galactosylated poly(ethylene glycol)-chitosan-graft-spermine

Cited 26 time in Web of Science Cited 31 time in Scopus
Authors
Kim, Ji-Hye; Minai-Tehrani, Arash; Kim, You-Kyoung; Shin, Ji-Young; Hong, Seong-Ho; Kim, Hye-Joon; Lee, Hee-Do; Chang, Seung-Hee; Yu, Kyeong-Nam; Bang, Yong-Bin; Cho, Chong-Su; Yoon, Tae-Jong; Yu, Dae-Yeul; Jiang, Hu-Lin; Cho, Myung-Haing
Issue Date
2012-02
Citation
Biomaterials, Vol.33 No.6, pp.1894-1902
Keywords
Gene therapyNon-viral gene deliveryHepatocyte targetingGalactosylated poly(ethylene glycol)-chitosan-graft-spermine
Abstract
Non-viral gene delivery systems based on polyethyleneimine (PEI) are efficient due to their proton-sponge effect within endosomes, but they have poor physical characteristics such as slow dissociation, cytotoxicity, and non targeted gene delivery. To overcome many of the problems associated with PEI, we synthesized a galactosylated poly(ethylene glycol)-chitosan-graft-spermine (GPCS) copolymer with low cytotoxicity and optimal gene delivery to hepatocytes using an amide bond between galactosylated poly(ethylene glycol) and chitosan-graft-spermine. The GPCS copolymer formed complexes with plasmid DNA, and the GPCS/DNA complexes had well-formed spherical shapes. The GPCS/DNA complexes were nanoscale size with homogenous size distribution and a positive zeta potential by dynamic light scattering (DLS). The GPCS copolymer had lower cytotoxicity than that of PEI 25K in HepG2, HeLa, and A549 cell lines at various concentrations and showed good hepatocyte-targeting ability. Furthermore, GPCS/DNA complexes showed higher levels of GFP expression in the liver in model mice after intravenous injection than naked DNA and metoxy-poly(ethylene glycol)-chitosan-graft-spermine as controls without remarkable fibrosis, inflammation, lipidosis, or necrosis. In a tumor suppression study, an intravenous injection of the GPCS/Pdcd4 complexes significantly suppressed tumor growth, activated apoptosis, and suppressed proliferation and angiogenesis in liver tumor-bearing H-ras12V mice. Our results indicate that the GPCS copolymer has potential as a hepatocyte-targeting gene carrier. (C) 2011 Elsevier Ltd. All rights reserved.
ISSN
0142-9612
URI
https://hdl.handle.net/10371/172330
DOI
https://doi.org/10.1016/j.biomaterials.2011.11.024
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College of Veterinary Medicine (수의과대학)Dept. of Veterinary Medicine (수의학과)Journal Papers (저널논문_수의학과)
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