Vaccaro, Mauro (2008) Amphiphilic Biostructures as Nanotechnological Devices in Cancer Diagnosis and Therapy. [Tesi di dottorato] (Inedito)

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Abstract

1.1 Aim of the Thesis This thesis has been carried out at the Department of Chemistry of Naples University, Italy, and at the Department of Physical Chemistry 1 at Lund University, Sweden, during the period 2005-2008. The aim of the thesis has been the design and the physico-chemical characterization of amphiphilic superstructures, such as micelles and liposomes, to be used as nano-devices in cancer diagnosis and therapy. The past quarter century of outstanding progress in fundamental cancer biology has not translated into even comparable advances in the clinic. Inadequacy in the ability to administer therapeutic moieties, so that they will selectively reach the desired targets with marginal or no collateral damage, has largely accounted for this discrepancy. Similar limitations apply to contrast agents for imaging applications. There are two synergistic goals that should be striven for to increase the efficacy per dose of any therapeutic or imaging contrast formulation: to increase its targeting selectivity and to endow the agent comprising the therapeutic or the diagnostic formulation with the means to overcome the biological barriers that prevent it from reaching its target. An ideal therapeutic system would be selective directed against cell clusters that are in the early stages of the transformation towards the malignant phenotype. The realization of such a system faces different challenges, including the identification of suitable bio-active molecules or chemical processes able either to deliver the therapeutic/contrast agent toward the cancer cells or to avoid biological and biophysical barriers. On these bases two different systems have been developed in the present research project: 1) The first system was formed by two amphiphilic unimers, one chelating a Gadolinium complex, that is the most common contrast agent used in Magnetic Resonance Imaging (MRI), the leading technique for the diagnosis of tumors, and the other one containing a peptide, the CCK8, showing high affinity for the cholecystokinin receptors which are overexpressed in different tumor pathologies. 2) The second system was formed by a unimer containing a pyridinium ring able to coordinate Ru(III) complexes, which offer new interesting perspectives in the selective attack of tumor metastases.

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