Project description
Nanoparticles light the way to ovarian cancer for early detection and treatment
Glycosylation (attachment of a polysaccharide) is a ubiquitous and highly regulated mechanism of secondary protein processing in cells. It modulates both the structure and function of the proteins and is intricately involved in signalling and ligand-receptor interactions. Alterations in glycosylation of secreted glycoproteins is associated with ovarian cancer, yet until now there were no selective assays to differentiate among the subtle differences in glycan chains. The EU-funded EARLYDETECT project has a patented platform to do just that. Scientists are using it to functionalise fluorescent nanoparticles with 'locks' for the cancer-associated glycan 'keys' they have identified. The result will be highly sensitive and selective detection of serum-associated glycosylation biomarkers of ovarian cancer simplified further with a fluorescent readout.
Objective
Every year, ovarian cancer (OC) kills more than 40 000 women in Europe and 150 000 worldwide. In large part this is due to the fact that most women are not diagnosed until advanced stages. There is an urgent unmet clinical need for screening tools for the early, accurate identification of OC. OC is associated with alterations in glycosylation of secreted glycoproteins, and as such, they can serve as early OC biomarkers. However, this knowledge has still not been translated into clinic due to the lack of assays that can differentiate subtle differences between glycan chains. For the first time, under the ERC consolidator grant-GLYCOSURF, we developed a synthetic glycan recognition platform that can sharply discriminate between different overall glycan structures (Patent No: WO2015/118294). Capitalizing on the knowledge of glycosylation variations in OC and our unique glycan recognition technology, we will be developing and clinically validating a new glycan-based test for detecting OC earlier and more effectively through a simple serum test. OC-associated glycans will be molecularly casted on fluorescent nanoparticles to create surface nanopockets with glycan receptors in a specific spatial arrangement to fit only OC-associated glycans. A microplate immunoassay with high sensitivity, selectivity and reproducibility will be developed, wherein the glycan-casted nanoparticles will provide a means for selectivity, signal amplification and fluorescent readout. Serum samples from OC patients and controls from women with benign tumours will be tested. The assay will be minimally-invasive, cost-effective and will be suitable for rapid, easily automatable, high-throughput screening, promoting swift translation into the clinical setting. This project offers therefore the potential to radically change the diagnostic standard of care for OC, ultimately saving lives and reducing the health, social and economic burden imposed by OC.
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Programme(s)
Funding Scheme
ERC-POC - Proof of Concept GrantHost institution
B15 2TT Birmingham
United Kingdom