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Development of nanodevices to monitoR bladder cAncer proGressiOn and drug resistaNce through extracellular vesicles delivered cargoes and activity

Acronym : DRAGON

Call : NanoTecMec 2024

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Topic

Bladder cancer (BC) has become a common cancer globally, with a significant social and financial burden, due to a necessity of continuous monitoring and recurrence treatment. Standard diagnostic workup relying on cystoscopy is invasive, expensive, and suboptimal in predicting the evolution to an aggressive or drug resistant disease. Diagnostic delays and errors cause avoidable patients invalidity and death and constitute a bottleneck in access to effective therapies.

DRAGON project targets the acute need for improving the status quo of BC management by proposing novel molecular markers for non-invasive–affordable-early-accurate disease prognosis/prediction based on multiparametric profiling of BC derived Extracellular Vesicles (EVs) from urine. EVs are complex, nanometer-scale biological systems that naturally multiplex diverse categories of biomolecules including active modulators of tumour growth. Their potential is largely unexplored as their size, complexity and heterogeneity evade the state-of-art analytical technologies.

 In DRAGON we will combine multiple EV molecules, including methylated DNA, regulatory RNAs, enzymes and metabolites, to capture heterogeneity of BC phenotypes and formulate informative panel(s) that will be validated for prognostic/predictive accuracy in prospective/retrospective cross-sectional multicentre study on selected BC cohorts. Multiomic EV fingerprints identified in BC progression models, will be integrated with miniaturized devices developed for EV separation and enrichment based on depleted zone isotachophoresis (dzITP), and optical biosensors based on nanoparticle-enhanced digital interferometric Reflective Phantom Interface.

These advanced nanotechnologies will reconnect high multiplex and (femtomolar) sensitivity, user-friendliness, and cost-effectiveness in a close-to patient diagnostics platform that will allow tailored surveillance and earlier, more targeted and conservative therapeutic measures.

  • Coordinator:

    Marco MOSCHINI, San Raffaele Hospital, Italy

  • Partners:
    • Marco BUSCAGLIA, Università degli Studi di Milano, Italy;
    • Lourdes MENGUAL, The Clinic Foundation for Biomedical Research-August Pi Sunyer Biomedical Research Institute, Spain;
    •  Thomas HANKEMEIER, Leiden University, The Netherlands
  • Collaborators:
    • (*) Yuliya SHAKALISAVA, EXIT071 B.V., The Netherlands
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