Descrizione del progetto
Le nanoparticelle illuminano la via alla diagnosi precoce e al trattamento del tumore ovarico
La glicosilazione (il legame di un polisaccaride) è un meccanismo onnipresente ed estremamente regolato di elaborazione secondaria delle proteine nelle cellule. Il meccanismo modula la struttura e la funzione delle proteine ed è strettamente coinvolto nella via di segnalazione e nelle interazioni ligando-recettore. Le alterazioni nella glicosilazione delle glicoproteine secrete sono correlate al tumore ovarico, eppure finora non vi erano test selettivi per distinguere le sottili differenze nelle catene di glicani. Il progetto EARLYDETECT, finanziato dall’UE, dispone di una piattaforma brevettata per fare proprio questo. Gli scienziati la stanno utilizzando per funzionalizzare le nanoparticelle fluorescenti con «serrature» per le «chiavi» di glicani correlate al tumore, da loro identificate. Il risultato sarà la rilevazione altamente sensibile e selettiva di biomarcatori della glicosilazione siero-correlati del tumore ovarico, ulteriormente semplificati con la lettura fluorescente.
Obiettivo
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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Meccanismo di finanziamento
ERC-POC - Proof of Concept GrantIstituzione ospitante
B15 2TT Birmingham
Regno Unito