Receptor-mediated delivery of lactosylated PEG siRNA conjugate (Lac-PEG–siRNA) complexed with poly-L-lysine (PLL). (A) Chemical structure of Lac-PEG–siRNA. (B) RNAi activities against firefly luciferase gene generated in human hepatoma HuH-7 cells. A significant decrease in the firefly luciferase expression was observed after transfection with Lac-PEG–siRNA (conjugate alone) and with Lac-PEG–siRNA complexed with PLL (polyion complex, PIC micelle) (right panel). Cellular uptake via asialoglycoprotein (ASGP) receptor-mediated endocytosis was confirmed using asialofetuin (ASF), which is the inhibitor for ASGP receptor. The inhibitor of endosomal acidification, nigericin, was used to confirm that the acid-labile linkage in the conjugate contributes to RNAi activity (left panel). Reproduced from Oishi et al. (2005). Copyright (2006) American Chemical Society.
