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Liver-Optimised Targeted Uptake System

Project description

Targeted nanoparticles for liver cancer treatment

Hepatocellular carcinoma is the most common form of liver cancer and one of the leading causes of cancer-related death worldwide. Current treatments offer limited efficacy, partly because drugs are not delivered specifically to tumour cells. The liver naturally overexpresses a receptor called ASGPR, which makes it an attractive target for precision drug delivery. With the support of the Marie Skłodowska-Curie Actions programme, the LOTUS project aims to develop liposomal nanoparticles that selectively bind ASGPR and deliver the cancer drug sorafenib directly to liver tumour cells. Combining ligand discovery, nanocarrier engineering, and preclinical validation, the project will assess targeting efficiency and therapeutic efficacy across liver cancer models with varying receptor expression levels.

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.

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HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships

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Call for proposal

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(opens in new window) HORIZON-MSCA-2025-PF

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Coordinator

UNIVERSITY COLLEGE LONDON
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 260 347,92
Address
GOWER STREET
WC1E 6BT London
United Kingdom

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Region
London Inner London — West Camden and City of London
Activity type
Higher or Secondary Education Establishments
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Total cost

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