High hepatocyte specificity of YSK13-C3-MEND by sensitivity toward activity of lipase. (a) A plot of ED50 for in vivo gene silencing of YSK05-MEND and YSK13-C3-MEND in hepatocytes and LSECs. For YSK13-C3-MEND, ED50 dose was not achieved in LSECs, this is indicated by the open circle representing the highest dose tested. (b) Effect of lipase inhibitors on CD31 gene-silencing activity in liver. Mice were i.p. injected with GSK264220A (30 mg/kg), orlistat (30 mg/kg), or vehicle and i.v. injected with siCD31 formulated in the YSK05-MEND or the YSK13-C3-MEND at a dose of 1 mg/kg. CD31 mRNA expression in liver tissue was quantified in 24 hours. Data are represented as the mean ± SD (n = 3). **P < 0.01 (by two-tail unpaired t-test). ED50, median effective dose; FVII, factor VII; LSEC, liver sinusoidal endothelial cell; MEND, multifunctional envelope-type nanodevice; PBS, phosphate-buffered saline.