Experimental studies aimed to assess the usefulness of nanoparticles as diagnostic and theranostic agents

During the last decade, significant advances have been performed in the field of nanomedicine both in the synthesis of novel nano compounds and in their biomedical applications. This thesis is focused on biomedical applications of nanoparticles characterized by diagnostic and / or therapeutic properties. Classes of nano compounds investigated in this thesis include iron oxide nanoparticles, characterized by the capability to affect the magnetic resonance signal of cells/tissues, and fluorescent particles detectable by optical imaging techniques. One of the nanoparticles investigated is characterized, in addition to diagnostic, by therapeutic properties thanks to its ability to generate heat, when stimulated by an alternating magnetic field. The last research field, joining diagnostic and therapeutic capabilities in a single nanocompound, has been recently defined theranostics. The aim of the thesis was to define and optimize some experimental procedures, that could be of general utility in testing diagnostic efficacy, toxicity and therapeutic efficacy of nanoparticles. Specifically the following nanocompounds have been studied: 1) iron oxide nanoparticle, presently in clinical trials, for lymph node metastasis detection (P904, Guerbet, France); 2) two lanthanide doped nanoparticles characterized by magnetic and upconversion properties (bimodal nanoparticles); 3) iron oxide nanoparticle, of biological origin (magnetosomes), characterized by diagnostic (detectability in MRI) and therapeutic properties (tumor ablation). The results obtained with the above mentioned nanoparticles have been reported in different chapters of the thesis. In particular, in Capther 3, experimental studies, performed with P904 used as MRI diagnostic agent, in a murine model of lymph node metastasis, have been reported. Results indicate high sensitivity of P904 in the detection of lymph node metastasis. In Chapter 4, experiments performed with upconverting lanthanide doped nanoparticles are described. Studies about cellular toxicity and cellular uptake in vitro as well as biodistribution studies in vivo have been performed. Our results demonstrate that the upconverting lanthanide doped nanoparticles are characterized by low toxicity and by the capacity to label cells in vitro. Moreover, our studies suggest that lanthanide doped nanoparticles have potential usefulness, in vivo, as liver MRI contrast agents. In Chapter 5, in vitro studies on magnetosomes interaction with cancer cell and the in vivo experiments with magnetosomes used as MRI contrast agent and theranostic agent, have been described. The experimental results demonstrate that magnetosomes, innovative and biologically synthesized nanoparticles, may have interesting theranostic properties as they are easily detectable in MRI and, at the same time, have the capability of release heat in the tumor tissue when stimulated by proper, oscillating magnetic fields.