title: Well-Defined Multivalent Ligands for Hepatocytes Targeting via Asialoglycoprotein Receptor.
abstract: Targeted delivery of therapeutic agents to hepatocytes is a particularly attractive strategy for the treatment of hepatocellular carcinoma and other liver diseases. The asialoglycoprotein receptor (ASGP-R) is abundantly expressed on hepatocytes and minimally found on extra-hepatic cells, making it an ideal entry gateway for hepatocyte-targeted therapy. Numerous multivalent ligands have been developed to target ASGP-R, among which well-defined multivalent ligands display especially high binding affinity to the receptor. Recently, several gene delivery systems based on such ligands for ASGP-R showed encouraging clinical results, drawing increasing interest in the scientific community and eventually promoting the improvement of current treatment for liver diseases. Here, we review ASGP-R targeting with a special emphasis on well-defined systems and properties such as the linker's length, hydrophilic-hydrophobic balance of the linker, and the spatial geometry of the scaffold. The present manuscript provides important guidelines for the design of multivalent ligands for ASGP-R.
authors.affiliation: Institute of Pharmaceutical Sciences, Department of Chemistry and Applied Biosciences, ETH Zurich , Vladimir-Prelog-Weg 1-5/10, 8093 Zurich, Switzerland.
authors.forename: Xiangang
authors.identifier: 0000-0001-8948-7879
authors.initials: X
authors.lastname: Huang
authors.affiliation: Institute of Pharmaceutical Sciences, Department of Chemistry and Applied Biosciences, ETH Zurich , Vladimir-Prelog-Weg 1-5/10, 8093 Zurich, Switzerland.
authors.forename: Jean-Christophe
authors.initials: JC
authors.lastname: Leroux
authors.affiliation: Department of Pharmacology and Therapeutics, McGill University , 3655 Prom. Sir-William-Osler, Montréal, Québec H3G 1Y6, Canada.
authors.forename: Bastien
authors.initials: B
authors.lastname: Castagner
mesh_terms: D000818:Animals; D037263:Asialoglycoprotein Receptor / Q000378:metabolism*; D004337:Drug Carriers / Q000737:chemistry* / Q000378:metabolism*; D022781:Hepatocytes / Q000378:metabolism*; D006801:Humans; D008024:Ligands
chemical_list: D037263:Asialoglycoprotein Receptor; D004337:Drug Carriers; D008024:Ligands