DEVELOPMENT OF NANOMATERIALS TO OPTIMIZE DRUG THERAPY IN CANCER PATIENTS: Synthesis and characterization of different nanocomposites

In this thesis, several types of nanocomposites have been developed. Starting from mesoporous zirconia nanoparticle (MZN) and its functionalization, and using it as common denominator, different systems for theranostic and orthopaedic applications have been produced. MZN has been functionalized with phospho-derivates to avoid organosilanes, usually employed in modification of several types of nanoparticles. To obtain a theranostic system, a nanocomposite of zirconia and cobalt ferrites, obtained by wet impregnation and thermal treatments, has been linked, through bis-phosphonic acids with tio-ending group, to gold nanoparticles, thanks to the collaboration of Prof M. Meneghetti, to obtain a system which is potentially able to perform magnetic and plasmonic hyperthermia, SERS and medical imaging. A deep study on physical-chemical properties of this composite was performed, varying quantities of cobalt ferrites introduced, doping only with iron, and modifying the surface with different phosphonic acids. Trials to obtain a porous structure with good magnetic properties for theranostic applications have been done: first we modify the procedure of wet impregnation and thermal treatments with lower temperature, after results obtained with MCX line at Elettra Synchrotron of Trieste, then we made single-domain magnetic seeds used as nuclei for the synthesis of mesoporous zirconia nanoparticles. Further improvement of the magnetic system was investigated at NTNU of Trondheim, in collaboration with G. Sing and D. Peddis, by synthetizing bi-magnetic core-shell structures, doping cobalt ferrites with zinc and nickel, and trying to obtain dielectric shell made of zirconia on core nanoparticles to further improve the possibility of embedding in MZN. Moreover, starting from evidences of layer organization of modified MZN on different surfaces, a systematic study has been performed. Several solvents and surfaces have been tested with drop casting and dip coating protocols. Then, to improve the linking, a covalent bond, employing EDC/S-NHS carbamide bonds, has been obtained, on modified titanium in different ways. Tests on biofilms growth have been conducted on the best surface. To improve the system for orthopaedic applications, silver nanoparticles have been synthetized inside pores channels of MZN (MZN@Ag). Several protocols have been tried to obtain silver only inside pores or strictly linked to MZN. Tests on the activity of silver modified zirconia have been performed on E. coli. Then, preliminary tests of linking of nanoparticles with biological molecules, such as antibodies, have been performed in order to evaluate if it was possible to work only with phosphonates instead of organosilanes as functionalizing moieties. However, these results represent only a preliminary study for the applications of several nanocomposites to biomedical field, and need further investigation for practical uses in daily treatments.