NFκB decoy delivery using dendritic poly(l-lysine) for treatment of endotoxin-induced hepatitis in mice

Yusuke Sugao, Kazuto Watanabe, Yuriko Higuchi, Ryohsuke Kurihara, Shigeru Kawakami, Mitsuru Hashida, Yoshiki Katayama, Takuro Niidome

Research output: Contribution to journalArticlepeer-review

13 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)4990-4995
Number of pages6
JournalBioorganic and Medicinal Chemistry
Volume17
Issue number14
DOIs
Publication statusPublished - Jul 15 2009

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

Fingerprint Dive into the research topics of 'NFκB decoy delivery using dendritic poly(l-lysine) for treatment of endotoxin-induced hepatitis in mice'. Together they form a unique fingerprint.

Cite this