“INVESTIGATING THE EFFECT OF SUPERPARAMAGNETIC IRON OXIDE NANOPARTICLES ON HYPERPROLIFERATIVE CELLULAR MODEL DISEASE”

The growing impact of nanotechnology in the field of medicine as a new potential clinical therapeutic agent requires the joint efforts of interdisciplinary research groups. Numerous questions must be faced. The main issues to be considered involve the mechanisms of interaction with the cells before, during and after their adhesion and internalization, the degradation pathways, cytotoxicity and the therapeutic efficacy. For these reasons, I attended to the construction of superparamagnetic iron oxide nanoparticles capable of providing compelling evidence of any of the abovedescribed key factors. To assess the utility of these nanoparticles, I chose to treat obesity and glioblastoma as two hyperproliferative disease models, which affect millions of adult every year worldwide. An attractive innovative possibility to approach the hyperproliferation can be envisaged in developing heating agents via magnetic nanoparticles. Thanks to their unique magnetic properties, superparamagnetic iron oxide nanoparticles now find large application as heating mediators for thermotherapy. These nanoparticles need to fulfil several criteria in order to be used as therapeutic agents in humans, including nontoxicity, heating efficiency and sensitivity of detection resulting in a capability of the nanoparticles to be confined preferentially at the diseased site. It is common believed in fact that alternative factors, including opsonisation, macrophage-mediated transport and passive delivery in general, might strongly affect the targeting efficiency and final destiny of nanoparticles. Using magnetic nanoparticles coated with protein-targeting biomarkers overexpressed by targeted tissue may be provided these factors. So the last step of the present work was focused on the construct of a peptidenanoconjugate to perform an accurate study of nanoparticle-membrane receptor in vivo. In summary, the general scope of this thesis was to develop an efficient nanoparticle for the investigation of the effect of thermotherapy mediated by magnetic nanoparticles on two hyperproliferative diseases. Several issues including nanoparticles synthesis, bio-functionalization, toxicity and the use as therapeutic agents have been thoroughly examinated and optimized. By taking advantage of the interdisciplinary view offered by synergistic chemical, 9 physical and biochemical approaches, I have designed a new nano-system suitable to explore new frontiers in the therapy of the hyperproliferative diseases. Of course, the clinical application in human treatments is the final goal of this and its related research. However, to reach such objective is necessary not only to design a suitable system for practical use, but also to assess and optimize the essential characteristics for specific effects such as safety, capability to get to the specific target, to provide useful signal amplification and to avoid the immunogenic system.