PREPARATION OF NANO- AND MOLECULAR COMPOUNDS FOR ANTITUMORAL APPLICATIONS TRIGGERED BY LIGHT

The PhD thesis comprises 5 research projects, all dealing with the preparation of compounds for antitumoral applications, involving different types of compounds: nanocomposite materials, organometallic complexes, and organic compounds. The antitumoral action of most of these systems was based on the photodynamic therapy (PDT), often to combine it with a secondary antitumoral strategy to enhance its efficiency. A smaller part of the thesis was instead devoted to the preparation of a luminescent metformin derivative to investigate the antitumoral activity of this antidiabetic drug. In the first project, the surface of gold nanostars (GNS) was functionalized with a polyamidoamine-Ru(II) complex to increase the PDT efficiency of the complex, i.e. to produce ROS upon irradiation, due to the metal-enhanced 1O2 generation promoted by GNS. Another possible advantage of such functionalized nanostructures that has not been studied yet is the possibility to combine PDT with plasmon photothermal therapy (PTT) promoted by the same GNS. Differently, in the second project, GNS were employed to decorate the external surface of HNT, aiming to obtain a nanocomposite carrier for small molecules loaded into the HNT tubular structure, whose release would be triggered by the local hyperthermia produced by GNS. The action of the released drug is combined with the PTT. The antitumoral drug selected in this thesis (mitoxantrone) can be replaced with an organic photosensitizing agent to introduce an additional PDT treatment. In the third project HNT were functionalized in their inner lumen to serve as carriers for hydrophobic photosensitizers, such as perfluorinated porphyrins (in their non-coordinated and Zn-coordinated form), well known for their PDT action. The second part of the thesis focuses on the preparation of organometallic and organic compounds and includes the last two projects. One concerns the preparation of a bioconjugate between a tris-cyclometalled Ir(III) complex and a peptide nucleic acid (PNA). This work aimed to obtain a multifunctional compound with anticancer activity based on a possible synergic effect between PDT, promoted by the Ir complex, and an antisense/antigene strategy induced by specific PNA sequences that can target RNA or DNA chains and interfere with their transcription. Finally, the last project was dedicated to the preparation of a luminescent molecule containing a terminal biguanide group to study how this moiety interacts with tumoral cells and can be related to the activity of the anti-diabetic drug metformin in inhibiting the proliferation of various types of tumors. Moreover, for three of these projects, a biological investigation at the cellular level was carried out, confirming their efficacy for antitumoral therapies.