Fucose-appended dendrimer/α-cyclodextrin conjugate as a novel NF-κB decoy carrier to Kupffer cells infulminant hepatitis mice induced by lipopolysaccharide

摘要

Fulminant hepatitis is a serious, life-threatening disorder andis associated with inflammatory cytokines produced by Kupffercells. However, a number of clinical trials for the treatment offulminant hepatitis did not show enough substantial benefits.Since NF-κB is a key mediator of inflammatory responsein Kupffer cells, NF-κB decoy would be an attractive candidatefor the treatment of fulminant hepatitis. Recently,Opanasopit et al. revealed that fucosylated protein is preferentiallytaken up by Kupffer cells via a fucose receptor (Fuc-R). Therefore, the fucosylation to NF-κB decoy carrier is one ofthe prominent approaches for Kupffer cell-selective delivery.We recently reported that thioalkylated mannose-modified starburst polyamidoamine (PAMAM) dendrimer/α-cyclodextrin conjugates(Man-S-α-CDE (G3)) has the potential for a novel antigenpresenting cell-selective siRNA carrier [1]. However, there is noreport on fucose-appended α-CDE as a Kupffer cell-selectiveNF-κB decoy carrier. Therefore, in the present study, we newlysynthesized fucosyl-oxypropyl-thio-propionylated α-CDE(Fuc-S-α-CDE (G2) (Fig. 1A)) and evaluated the potential of Fuc-S-α-CDE (G2)/NF-κB decoycomplex for the treatment of fulminanthepatitis [2].