Well-Defined Multivalent Ligands for Hepatocytes Targeting via Asialoglycoprotein Receptor
- PMID: 27966887
- DOI: 10.1021/acs.bioconjchem.6b00651
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.
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