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

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.

Dendritic poly(l-lysine) formed a complex with the NFκB decoy oligonucleotide. After intravenous injection of the complex into hepatitis mice, the inflammatory reaction was suppressed.Figure optionsDownload as PowerPoint slide