Research team: Giovanni Signore, Gianmarco Ferri, Pasquale Mastella, Elisa Ottalagana

Early diagnosis still represents a critical discriminator between poor and favourable prognosis. Most tumors are asymptomatic in their early stages, thus diagnosis is performed based on ex vivo evaluation of dysregulated biochemical parameters. Poor sensitivity of these assays can significantly delay tumor detection An intriguing alternative relies on detection of circulating biomarkers of exclusive tumor derivation. Unfortunately, these highly informative biomarkers are usually too diluted in blood to be suitable for conventional detection strategies.

The proposal aims at changing this perspective by developing a nanosensor that can quantify trace levels of tumor-secreted biomarkers in blood. The sensor will be based on a nanoparticle that spontaneously disassembles in the bloodstream upon irreversible interaction with its biomolecular target. This process generates several excretable metal reporters, easily quantifiable by mass spectrometry (ICP-MS) or luminescence assays. It is expected that sub-femtomolar detection limits could be achieved with this strategy.
Nanosensor will be engineered to detect circulating EGFRvIII. This receptor is a truncated version of EGFR and represents an ideal biomarker since it is only expressed by an aggressive subset of gliomas and is completely absent in physiologic conditions or after tumor resection. Moreover, it is present on tumor mass and on the surface of glioma-secreted exosomes, that could represent an excellent circulating target.

Sensitivity of proposed nanosensor towards EGFRvIII will be validated ex vivo by the end of the project. Additionally, suitability of the sensor as a tool for precise tumor localization and targeted delivery of contrast agents will be assessed on tumor organoids.