SUPERPARAMAGNETIC IRON OXIDE NANOPARTICLES (SPIONS): DESIGN AND SYNTHESIS OF NEW NANOCONJUGATES

Superparamagnetic Iron Oxide Nanoparticles (SPIONs) have demonstrated great promise for diagnostic and therapeutic applications. Thanks to their magnetic properties and to their size, comparable to that of biologically objects, they are very useful for biomedical applications, such as, for example, automated DNA extraction, targeted gene delivery, magnetic resonance imaging (MRI), and magnetic field induced hyperthermia for cancer therapy.For these applications, SPIONs must be coupled with targeting agents, therapeutic drugs, and other functional probes. Hence, the need to develop efficient synthetic strategies for the conjugation of molecules to SPIONs is an important and appealing target. The strategies used can involve passive noncovalent adsorption on the outer particle surface or the formation of a more stable covalent bond by using appropriate heterobifunctional linkers, in which one functional group specifically binds the nanoparticle, while the other reacts with the biomolecule in order to form the new nanoconjugate. In this thesis, the use of an heterobifunctional linkers containing an isocyanate moiety as new functional group able to directly bind SPIONs will be shown. We were able to demonstrate that the NCO moiety is able to directly reacts with the surface hydroxyl groups exposed on the outer nanoparticles surface leading to a covalent carbamate-like bond. Comparison with classical non-covalent and covalent anchoring methodologies were also performed. To further confirm the possible application of this new anchoring methodology, new SPION-PNA (Peptide Nucleic Acid, mimics of natural oligonucleotides) nanoconjugates were synthesized and their binding affinity towards complementary DNAs were evalueted.