Liver-Optimised Targeted Uptake System

Objective

This project will deliver a lipid-based formulation that is targeted to the the asialoglycoprotein receptor (ASGPR) for effective and stratified treatment of hepatocellular carcinoma (HCC), which is one of the leading causes of cancer related deaths worldwide. We will identify high-affinity glycopeptide ligands to ASGPR and test their capacity to target HCC cells. Optimised glycopeptide hits will be conjugated to PEGylated liposomal nanocarriers for targeted delivery of the kinase inhibitor, sorafenib. The approach combines ligand discovery, peptide chemistry, nanocarrier engineering, and preclinical validation in vitro and in vivo. The project will assess receptor selective uptake, therapeutic efficacy, and stratification potential in HCC models with higher and lower ASGPR expression. The innovation of this project is in going beyond conventional peptide ligands to develop novel glycopeptide targeting motifs that improve upon existing motifs used for siRNA delivery to the liver. The project is based upon strong preliminary findings from the host lab at UCL and will serve as a springboard for a nee research theme of targeted kinase inhibitor delivery for cancer. This fellowship will enhance the researcher’s expertise in glycopeptide ligand discovery, translational drug delivery, and advanced cancer models, while strengthening UCL’s leadership in peptide-directed nanomedicine. The results will have wider impact for precision oncology and hepatic delivery of novel therapeutics. This aligns closely with MSCA’s mission of scientific excellence, mobility, and career development.