AIM:To develop a hepatocyte targeting pH-sensitiveliposome for drug delivery based on active targetingtechnology mediated by asialoglycoprotein receptors.METHODS:Four types of targeting molecules with galactoseresidue were synthesized and mixed with pH-sensitive lipidsDC-chol/DOPE to prepare liposome with integrated propertyof hepatocyte specificity and pH sensitivity.Liposome 18-gal was selected with the best transfection activity throughcellular uptake experiment.Property analysis was madethrough experiments of competitive inhibition of receptors,red blood cell hemolysis,in vitro cytotoxicity test by MTSassay and mediation of inhibitory effects of antisensephosphorothioate ODN on gene expression,etc.RESULTS:Liposome 18-gal had the desired properties ofhepatocyte specificity,pH sensitivity,low cytotoxicity,andhigh transfection efficiency.CONCLUSION:Liposome 18-gal can be further developedas a potential hepatocyte- targeting delivery system. AIM: To develop a hepatocyte targeting pH-sensitive liposomes for drug delivery based on active targeting technology mediated by asialoglycoprotein receptors. METHODS: Four types of targeting molecules with galactose residue were synthesized and mixed with pH-sensitive lipids DC-chol / DOPE to prepare liposomes with integrated propertyof hepatocyte specificity and pH sensitivity. Liposome 18-gal was selected with the best transfection activity throughcellular uptake experiment. Property analysis was made through experiments of competitive inhibition of receptors, red blood cell hemolysis, in vitro cytotoxicity test by MTS Assay and mediation of inhibitory effects of antisense phosphorothioate ODN on gene expression, etc.RESULTS: Liposome 18-gal had the desired properties of hepatopecificity, pH sensitivity, low cytotoxicity, and high transfection efficiency. CONCLUSION: Liposome 18-gal can be further developedas a potential hepatocyte-targeting delivery system.