PRECISE - APtameR based thEragnostiC strategy to impair the crosstalk between glIoma Stem cElls and their niche
Tipo di progetto:
Glioblastoma (GBM) has remained a disease with one of the worst prognoses and one of the most devastating outcomes over the past decades. Despite advancements in surgical methods, radiation therapy and chemotherapy, GBM patients have a current life expectancy of 14 to 15 months after diagnosis. The presence of the blood-brain-barrier (BBB) makes GBM treatment and diagnosis extremely challenging. Survival of GBM patients is seriously hampered by glioma stem cells (GSCs) due to their devastating therapy-resistance and self-replicating capacity. The properties of GSCs rely on a dynamic process of communication between them and their niches, a protective microenvironment in GBM. Extracellular vesicles (EVs) produced by GSCs are central in the inter-cellular communication with their hypoxic, vascular, and immune niches and hence maintain high intra-tumoral heterogeneity. EVs are accessible in biofluids and may contain valuable biomarkers for GBM patient diagnosis and follow-up. Aptamers, short synthetic DNA or RNA oligonucleotides are promising candidates for targeted therapies and diagnosis in brain diseases for their high specificity and stability, the ability to cross the BBB, lack of toxicity and immunogenicity. The present project (PRECISE) aspires at the development of novel therapeutic aptamer conjugates able to impair molecular mechanisms underlying the communication between GSCs and their niches. We will also exploit the possibility of a novel aptamer-based approach for the detection of GSC-derived EVs by a Surface Enhanced Raman Scattering (SERS) biosensing strategy in a microfluidic chip for early detection of GBM patients. These aims will be pursued because of a recently identified aptamer, A40s, that selectively targets GSCs and GSCs derived EVs. The investigation will increase knowledge on the mechanisms that regulate GSCs and will foster the identification of novel therapeutic (molecular and immunological) and diagnostic strategies, specifically targeting the GSCs. Finally, we will implement dissemination of the obtained results to “expert” and “non-expert” audience to promote awareness of GBM disease in the social community. To achieve these goals, skills and knowledge in different scientific fields are put in place. Three Research Units (RU) characterized by different but complementary scientific expertise will be involved. It is expected that the PRECISE outcomes will move from basic research to translation medicine providing significant scientific benefits for the development of possible application as GBM therapeutic and diagnostic approach.
- Alessandro Chiado'. (Responsabile Scientifico)
|Costo totale progetto:
|Contributo totale progetto:
|Costo totale PoliTo: