Design, synthesis and characterizations of hybrid nanosystems: nanomedicine applications in theranostics

The research project discussed in this PhD thesis concerns the development of drug delivery and theranostic systems for nanomedicine applications in cancer treatments. In the first part, polymeric nanoparticles have been exploited as drug delivery systems for the treatment of Glioblastoma Multiforme. For this purpose, two different biomolecules, in one case Cholotoxin, a small peptide, and in the other case an antiPDGFRs-aptamer (GINT.4), have been employed as targeting agents conjugated on the polymeric nanoparticles surface. The second section of the project has been focused on the development of metallic nanoparticle for photothermal therapy, a cancer treatment consisting in the exposition of body tissue to an increasing of temperature (42-45°C) to induce cytotoxic effects on cancer cells. For this purpose, gold nanorods (GNRs) have been investigated as photothermal agent for the treatment of Barrett’s esophageal. On the other hand, one pot-synthesis of chitosan coated magnesium nanoparticle has been fine-tuned in order to obtain high biocompatible nanoparticles characterized by a promising unexpected photothermal behaviour. In the last part of the project, the synthesis of multicomponent nanosystems suitable for multimodal imaging or theranostic agents have been investigated. Two different multifunctional nanomaterials based on the incorporation of iron oxide and gold nanoparticles in the same nanosystem, have been realized. The first system consisted in dumbbell-like gold-iron oxide nanoparticles coated with chitosan that showed photothermal behaviour and also good capabilities as photoacoustic imaging contrast agents. The second system consisted in core−shell Fe3O4@SiO2@Au NPs entrapped in polymeric nanoparticles decorated with folic acid, have been tested in vivo for photoacoustic and magnetic resonance imaging detection of ovarian cancer.