Descrizione del progetto
Nanoparticelle catalitiche per l’attivazione localizzata di farmaci
Nel rilascio controllato dei farmaci, i nuovi approcci di somministrazione focale possono integrare i sistemi convenzionali di somministrazione e le strategie dei profarmaci al fine di evitare effetti avversi e farmacoresistenza, oltre che per aumentare la loro l’efficacia. Il progetto GOLDEN, finanziato dall’UE, propone di eludere l’apparato metabolico delle cellule e di produrre molecole bioattive in siti specifici del corpo utilizzando nanoparticelle metalliche (NP, Metallic Nanoparticle). Tali NP a base d’oro fungono da catalizzatori biocompatibili e possono essere ingegnerizzate per raggiungere specificamente le cellule tumorali, convertendo in farmaci i precursori bioattivi somministrati per via sistemica. I ricercatori del progetto utilizzeranno i pesci zebra come modello per testare l’efficacia della strategia basata sulle NP di GOLDEN nell’attivazione di coloranti e neuromodulatori a livello cerebrale, aprendo la strada al trattamento di disturbi localizzati e dolore cronico.
Obiettivo
"Despite recent advances in cancer therapy, many challenges remain to reduce the systemic adverse effects of antineoplastic therapeutics. A major goal in the field is to make nanomedical devices that could bypass the metabolic machinery of cells and perform tasks that are not possible with biological entities, such as the manufacture of bioactive molecules at specific locations in a continuous, atomically precise manner. The use of metallic nanoparticles (NPs) as biocompatible catalysts provides the opportunity to carry out abiotic catalysis inside cancer cells or tissues. Such bioorthogonal reactivity opens up new unprecedented ways of mediating artificial transformations in complex biological systems.
Solid supported Au-NPs have recently demonstrated a novel, very promising role as heterogeneous catalysts able to generate bioactive compounds in biological environments. Herein I propose an innovative approach to develop catalytically- active Au-NPs immobilized within implants or ""protected"" under self-assembling monolayers to enable the activation of systemically-administered bioactive precursors at specific locations via novel Au-mediated deprotection chemistry. To confirm the in vivo functional capabilities of the devices, I will test the capacity of the novel devices to activate dyes and neuromodulators in the brain of zebrafish. This highly innovative multidisciplinary approach could offer a unique and safe method to release bioactive molecules in exact anatomical locations for the treatment of localized disorders including cancer or chronic pain and, in doing so, promote Scientific Excellence in Europe. As the recipient of the advanced training required to perform such a novel programme of research and developer of such tools, at the end of this fellowship I will reach a privileged position for establishing myself as an independent researcher and starting cross-disciplinary collaborations with academics and Pharma across Europe."
Campo scientifico
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Meccanismo di finanziamento
MSCA-IF-EF-ST - Standard EFCoordinatore
EH8 9YL Edinburgh
Regno Unito