Abstract
Lo sviluppo di agenti di contrasto (CA) “green” per la risonanza magnetica (RM) utilizzata per la rilevazione di malattie specifiche, sta rapidamente diventando un imperativo medico diagnostico, al fine di evitare la tossicità sull'uomo e sull'ambiente causata ad oggi utilizzando allo scopo derivati del costoso e raro elemento gadolinio. L’obiettivo del progetto FUN CODE è affrontare questo problema urgente. L'aspetto innovativo del progetto è l'uso di nanoparticelle di silice fluorurate (SNP) come CA per la RM a base di fluoro (19F_MRI), una tecnica, ad alta risoluzione spaziale alternativa alla RM classica, che consente la rilevazione in vivo in profondità con elevata sensibilità e non richiede isotopi radioattivi. Le SNP preparate saranno mesoporose per investigarne le capacità di stoccaggio di presunti farmaci. FUN CODE produrrà così nuovi (nano) sistemi multifunzionali per imaging e per multi-trasporto di farmaci per terapie combinate all'interno della stessa SNP diagnostica, con un impatto significativo in nanotecnologia e nanomedicina.
Results achieved
The FUN CODE (Fluorinated Nanoparticles as Green Contrast Agents for ^19F MRI and Drug Delivery) project successfully achieved its main objective of developing innovative fluorinated silica nanosystems for theranostic applications, combining diagnostic imaging by ^19F magnetic resonance imaging (^19F MRI) with drug delivery. By integrating the complementary expertise of the University of Trieste and the University of Bologna in nanomaterials synthesis, supramolecular chemistry and advanced spectroscopy, the project led to a new class of multifunctional fluorinated silica nanoparticles. A major achievement was the design and synthesis of a new family of amphiphilic fluorinated ligands specifically tailored for ultrasmall silica nanoparticles. These ligands combine three functional elements: a fluorinated segment providing the ^19F MRI signal, a hydrophilic polyethylene oxide chain ensuring water dispersibility, and a triethoxysilane group enabling covalent anchoring to the silica surface. Optimized synthetic routes yielded robust ligands suitable for preparing highly stable nanomaterials. The project established reproducible protocols for synthesizing ultrasmall silica nanoparticles with diameters of 3–5 nm. Optimization of reaction parameters enabled precise control of nanoparticle growth while preserving excellent colloidal stability. The resulting nanoparticles exhibited crystalline silica cores of about 3.6 nm and high surface coverage of fluorinated ligands, representing an important step toward biomedical applications. Comprehensive characterization by TEM, DLS, TGA, and ^1H, ^19F and DOSY NMR confirmed the successful preparation of the nanosystems and the integrity of their organic shell. These analyses also revealed the presence of strongly associated ligand precursors trapped within the fluorinated monolayer, an unexpected supramolecular organization contributing to the distinctive structural and functional properties of the nanoparticles. The nanoparticles were evaluated as potential ^19F MRI probes through measurements of ^19F nuclear relaxation times (T₁ and T₂), which demonstrated properties fully compatible with MRI tracking applications. These results indicate that the nanosystems are promising alternatives to conventional gadolinium-based contrast agents, while offering improved stability and reduced environmental concerns. The University of Bologna investigated the host–guest properties of the fluorinated nanoparticles using Electron Paramagnetic Resonance (EPR) spectroscopy and specifically designed nitroxide spin probes. Probes differing in size, lipophilicity and fluorine content enabled quantitative characterization of supramolecular interactions within the nanoparticle shell and determination of association constants. The study demonstrated the ability of the nanoparticles to incorporate drug-like molecules through non-covalent interactions. Drug delivery capability was further assessed using DMPC liposomes as model biological membranes. EPR experiments showed that the probes preferentially partition into the nanoparticles while remaining efficiently transferable to lipid vesicles, demonstrating that the nanosystems can both encapsulate and release guest molecules under biologically relevant conditions. These findings support their potential as nanocarriers for controlled drug delivery. An unexpected and particularly valuable outcome emerged from nanoparticles prepared from partially converted ligand mixtures, which displayed exceptionally high affinity for hydrophobic molecules, behaving as efficient molecular "flypaper". This unforeseen property opens new opportunities for capturing, encapsulating and retaining hydrophobic compounds, significantly expanding the original scope of the project. Overall, the FUN CODE project delivered an innovative platform of ultrasmall fluorinated silica nanoparticles with excellent potential for both ^19F MRI and drug delivery. Beyond meeting its original objectives, the project generated new scientific knowledge, strengthened collaboration between the participating groups, established valuable international partnerships, and laid the foundations for future biological studies and the development of multifunctional theranostic nanomaterials with strong translational potential.Dettagli del progetto
Responsabile scientifico: Paola Franchi
Strutture Unibo coinvolte:
Dipartimento di Chimica "Giacomo Ciamician"
Coordinatore:
Università degli Studi di TRIESTE(Italy)
Contributo totale Unibo: Euro (EUR) 67.899,00
Durata del progetto in mesi: 24
Data di inizio
16/10/2023
Data di fine:
28/02/2026
