Biomedical applications of inorganic nanoparticles: Magnetic Resonance Imaging and Hyperthermia.

Inorganic nanoparticles have been extensively used in biomedical applications as a result of their electronic, optical, and magnetic properties that are derived from their nanometer size and composition. Their magnetic characteristics are crucial for the successful performance in applications such as magnetic resonance imaging (MRI), drug delivery, cellular signaling, and hyperthermia. MRI is one of the most powerful imaging techniques for living organisms as it provides images with excellent anatomical details based on soft-tissue contrast and functional information in a non-invasive and real-time monitoring manner. Among the different kinds of contrast agents currently available for clinical diagnosis, Gd-based contrast agents, specifically Gd (III) chelates, are used as positive magnetic resonance imaging (MRI) contrast agent. However, they generally induce the risk of nephrogenic systemic fibrosis (NSF) due to the dissociated Gd3+ ions from Gd (III) chelates. To avoid this problem, novel positive MRI contrast agents based on MnO have been developed, allowing low toxicity, high sensitivity, and active targeting when conjugated with biomolecules (antibodies). During this work, the synthesis and characterization of MnO nanoparticles as positive contrast agents (T1) for MRI were carried out. Differences in size and morphology (round, star-like, cubic) were found by varying the reaction parameters such as solvent (1-hexadecene, 1-octadecene), temperature (280 °C, 300 °C) and reaction time (15, 30, 60 minutes). In order to determine their contrast enhancement, T1-weighted images were acquired in vitro at different concentrations. Furthermore, to study their biocompatibility, up-take, proliferation and cytotoxic assays were done in culture of endothelial cells SVEC4-1. To assess their biodistribution and wash out time, studies in vivo were carried out using a colitis induced murine model with 3% Dextran Sodium Sulfate (DSS) in drinking water. Data acquired showed a selective accumulation to inflammatory site in a short time suggesting a potential applicability for the diagnosis of the Inflammatory Bowel Disease (IBD). On the other hand, regarding the use of nanoparticles for hyperthermia, it’s well known that the conversion of electromagnetic energy into heat by nanoparticles has the potential to be a powerful, non-invasive technique for biotechnology applications but poor conversion efficiencies have hindered practical applications so far. However, it has been demonstrated that it’s possible to reach a significant increase in the efficiency of magnetic thermal induction by nanoparticles taking advantage of the exchange coupling between a magnetically hard core and magnetically soft shell to tune the magnetic properties of the nanoparticle and maximize the specific loss power. In an attempt to develop nanoparticles with high thermal energy transfer capability, GdFe3O4 nanoparticles were synthesized. To assess their thermal efficiency in vivo, the nanoparticles were injected in NODSCID mice with U87MG xenograft. By using MRI, T1 maps were obtained using a turbo-spin echo inversion-recovery sequence with respiration gating. Biodistribution experiments were carried out and subsequently, ion concentration in organs of interest (liver, spleen, kidneys) and tumor were measured ex vivo by using ICP-MS technique. Finally, changes in temperature and Specific Absorption Rate (SAR) were determined in order to establish their thermal efficiency. Results obtained showed these novel nanoparticles can be used as a promising tool for hyperthermia.