Design of functional colloidal magnetic nanoparticles for biomedical applications

Nanostructured materials have been the focus of scientific interest in recent years, because of the peculiar properties displayed by matter in nano-size form. The interest has been growing steeply since possible applications in biomedical fields have shown to be realistic. The interaction of magnetic nanoparticles with applied magnetic field gradients makes these particles attractive for their potential applications in biomedical imaging, diagnostic, and therapy. In this context, a great advantage are the superparamagnetic properties that can be exhibited by the nanoparticles. They behave as paramagnetic centres with high magnetic moment at room temperature, as it arises from the coupling of many atomic spins. After eliminating the external magnetic field, the particles no longer show magnetic interaction, thus reducing the possibility of particle aggregation; this feature is especially important for their applications. Biomedical use of magnetic nanoparticles imposes their uniform dispersion and stability in the biological fluids; moreover their size range should easily permit cell internalization through pinocytosis or endocytosis. Therefore, surface modification, via coating or encapsulation, is widely employed to improve nanoparticles properties and for immobilization of functional molecules. Magnetic nanoparticles have garnered widespread attention in recent years to develop and understand synthetic means to control their size, magnetic behaviour, and chemical reactivity. Simultaneously tuning surface chemistry and physical properties enable preparation of functional magnetic nanoparticles. Recent advances in synthesis have allowed to easily prepare a wide range of magnetic nanoparticles though aqueous or non aqueous approaches. It has been widely shown that the non-aqueous routes are more efficient in producing stable colloidal nanoparticles with narrow size distribution, high crystallinity, tunable size and shape. However, this approach typically produces hydrophobic nanoparticles limiting their applications in biological and medical fields. Thus, the transformation of these hydrophobic nanoparticles into hydrophilic is a crucial step toward their widespread use. The aim of the present PhD research project is to give a contribution to implement synthetic approaches to develop novel colloidal magnetic nano-architectures with applications in biomedical field. In particular, the research moves along two principal themes. From one side it has been investigated the possibility to tune magnetic nanoparticles size and properties through appropriate synthetic methodologies. From the other side, since the selected synthetic approach provides hydrophobic nanoparticles, particular attention has been devoted to the surface modification with organic and inorganic coatings in order to convert them into water dispersible systems. To this end, a multi-technique approach is used. A first structural analysis is performed by wide-angle X-ray Diffraction to obtain information about the crystalline phases and the crystallite size (coherent domain). Direct images of the samples, obtained by Transmission Electron Microscopy observations allowed an evaluation of the particle sizes, their distribution and the homogeneity of the particle dispersions. In order to study the magnetic-nanoparticles/coating interface, studies with FT-IR spectroscopy have been performed on hydrophobic nanoparticles and on all the systems in which the surface modification has been applied. To investigate the textural properties of the silica based composites nitrogen physisorption measurements have been performed in combination with low-angle X-ray diffraction to evidence the ordered porosity. Magnetic measurements have been acquired in order to understand how the different chemical composition, size and coatings can affect the magnetic properties of nanoparticles. All the measurements have been carried out at the Department of Chemical and Geological Sciences at the University of Cagliari.