SYNTHESIS OF MAGNETIC AND OPTICAL NANOMETRIC PROBES FOR THERANOSTIC APPLICATIONS

The aim of this Ph.D thesis is the development of new nanometric compounds that could find possible theranostic applications in the field of nanomedicine. To this end different multimodal agents, based on magnetic iron oxide nanoparticles or poly(amidoamine)s were synthesized and characterized. To this aim we first synthesized a new luminescent metallopolymer for photodynamic therapy (PDT), based on an amphoteric and biocompatible polyamidoamine, PhenISA, to which a new organometallic Ir complex was conjugated. This polymer was able to self-assemble into nanoparticle while the Ir complex could, upon light absorption, give rise to triplet metal to ligand charge transfer excited states that can both radiatively decay, providing optical luminescence, or react with 3O2, producing cytotoxic reactive oxygen species, allowing for both imaging and PDT applications. These properties were tested by cell uptake assays and prelaminar cytotoxicity studies. Poly(amidoamine)s functionalized with different metal complexes (namely Ru and Pt) were also investigated (Chapter 1). We then prepared a new magneto-optical probes and sensitizers for photodynamic therapy. This bimodal probe was constituted by a magnetic iron oxide core and a silica shell grafted with a luminescent Re complex, acting as both optical emitter and PDT sensitizer. The silica shell was also coated by a poly(ethyleneglycol) layer to reduce the toxicity and improve the colloidal stability of the nanoprobe. The nanocomposite photophysical properties were then tested, and the cellular uptake and light-activated cytotoxicity were subsequently characterized on HeLa cells (Chapter 2). As a next work we presented a new strategy to bind peptide nucleic acids (PNA) onto the surface of iron oxide nanoparticles, that could find future application in combining the nanoparticle magnetic properties with the PNA specific targeting ability. Two different synthetic pathways were investigated, and an extensive magnetic characterization was performed to check for any influence of the conjugation strategy on the nanoparticles initial magnetic properties (Chapter 3). During my abroad period in EMPA St.gallen (CH) I worked on the possible application of magnetic nanoparticle for blood purification applications. We first developed a proof of concept study on the theranostic potential of magnetic blood purification applied to sepsis using. Bacterial removal could not only directly improve the condition of sepsis-ill patients but also help in decreasing the time needed for effective diagnosis and treatment. To this end we used commercial magnetic nanoparticles functionalized with newly developed human IgG1 monoclonal antibody against poly-N-acetylglucosamine (PNAG), a key component of the bacterial cell wall. We investigated both the nanoparticles magnetic separation efficiency and degradation properties, as well as their biocompatibility and bacteria removal capability (Chapter 4). We then synthesized hydrophobic iron oxide and iron carbide nanoparticles that were subjected to an emulsion electrospinning procedure to synthetize magnetic nanoclusters. Their properties were then tested along with those of some commercial magnetic nanoparticles, for magnetic blood purification applications, checking biocompatibility, degradability in model buffers and separation efficiency to find the best candidate for future applications (Chapter 5). Finally we synthesized and characterized a new nanoparticle stabilizer based on a catechol functionalized amphoteric poly(amidoamine) and developed its conjugation reaction to iron oxide nanoparticles, using both a one-step and a two-step reaction, aiming at counteracting the inherent nanoparticle hydrophobicity that is the main drawback of the commonly used thermal decomposition. A second polymer, endowed with fluorescent properties, was also prepared and employed (Chapter 6).