TY - JOUR
T1 - NFκB decoy delivery using dendritic poly(l-lysine) for treatment of endotoxin-induced hepatitis in mice
AU - Sugao, Yusuke
AU - Watanabe, Kazuto
AU - Higuchi, Yuriko
AU - Kurihara, Ryohsuke
AU - Kawakami, Shigeru
AU - Hashida, Mitsuru
AU - Katayama, Yoshiki
AU - Niidome, Takuro
N1 - Funding Information:
This research was supported by a Grant-in-Aid for Exploratory Research (No. 18650124) and a Grant-in-Aid for Scientific Research (B) (No. 19300172) from the Japan Society for the Promotion of Science (JSPS).
Copyright:
Copyright 2009 Elsevier B.V., All rights reserved.
PY - 2009/7/15
Y1 - 2009/7/15
N2 - Mono-dispersed, 6th generation dendritic poly(l-lysine) (KG6) forms a stable complex with plasmid DNA and this complex can circulate in vivo for extended times before the DNA finally accumulates in the liver. In this study, we attempted to use KG6 as a carrier of NFκB decoy oligonucleotide to the liver to treat hepatitis, induced by lipopolysaccharide and d-galactosamine. KG6 formed a complex with the NFκB decoy. Serum aspartate aminotransferase and alanine aminotransferase were dramatically suppressed in the hepatitis mouse model after intravenous injection of KG6/NFκB decoy complexes. Expression levels of several cytokines and proteins related to the inflammatory reaction were also suppressed by intravenous administration of KG6/NFκB decoy complexes. Because [32P] NFκB decoy was found in non-parenchymal cells after intravenous injection, KG6 has been shown to be a promising carrier molecule of various oligonucleotides to non-parenchymal liver cells, including Kupffer cells.
AB - Mono-dispersed, 6th generation dendritic poly(l-lysine) (KG6) forms a stable complex with plasmid DNA and this complex can circulate in vivo for extended times before the DNA finally accumulates in the liver. In this study, we attempted to use KG6 as a carrier of NFκB decoy oligonucleotide to the liver to treat hepatitis, induced by lipopolysaccharide and d-galactosamine. KG6 formed a complex with the NFκB decoy. Serum aspartate aminotransferase and alanine aminotransferase were dramatically suppressed in the hepatitis mouse model after intravenous injection of KG6/NFκB decoy complexes. Expression levels of several cytokines and proteins related to the inflammatory reaction were also suppressed by intravenous administration of KG6/NFκB decoy complexes. Because [32P] NFκB decoy was found in non-parenchymal cells after intravenous injection, KG6 has been shown to be a promising carrier molecule of various oligonucleotides to non-parenchymal liver cells, including Kupffer cells.
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U2 - 10.1016/j.bmc.2009.05.081
DO - 10.1016/j.bmc.2009.05.081
M3 - Article
C2 - 19539484
AN - SCOPUS:67650046793
SN - 0968-0896
VL - 17
SP - 4990
EP - 4995
JO - Bioorganic and Medicinal Chemistry
JF - Bioorganic and Medicinal Chemistry
IS - 14
ER -
