Preparation and Chemical-Physical Characterization of Nanosystems for Molecular Magnetic Resonance Imaging (MRI)

In this PhD thesis different issues concerning the nanosystems for molecular MRI applications have been taken into account. Initially, the magnetic and chemical-physical behaviour of superparamagnetic iron oxide nanoparticles (SPIONs) have been taken into account, mainly aiming to increase the magnetic moment and the saturation magnetization value of the NP. Ultrasmall superparamagnetic iron oxide nanoparticles (USPIONs) functionalized with metal-carbamato complexes were synthesized and characterized, specifically Ti(O2CNR2)4 (R = Et, iPr) and Nb(O2CNEt2)4. The surface analysis was performed by means of FT-IR spectroscopy, the dimensional analysis by TEM microscopy and the magnetic behaviour was investigated by SQUID magnetometer (Chap. 3). Then, the issue of the nanoparticle surface functionalization for molecular imaging application has been tackled. Cystine-coated ultrasmall nanoparticles (Cy-NPs) were prepared and characterized. Their chemical-physical properties were investigated by means of FT-IR spectroscopy, microscopy (TEM, HTEM, AFM) and by SQUID magnetometry. The relaxometric properties of Cy-NP aqueous solutions were investigated by means of relaxometry and MRI measurements performed at 7 T. Moreover, the toxicity of Cy-NPs on human immune cells ex vivo was studied (Chap. 4). Finally, a different nanosystem has been taken into account in order to perform a targeted-functionalization with folate molecules for MRI detection of human ovarian cancer cells. The apoferritin loaded with Gd-HPDO3A, which is an extracellular contrast agent commercially available, was prepared and successfully conjugated with folate molecule. Its behavior as molecular MRI probe was studied preliminarily, in vitro on human ovarian cancer cells (IGROV-1) and in vivo in nude mice (Chap. 5).