Synthesis of γ-Fe(2)O(3)-SiO(2) composite nanoparticles targeting magnetic resonance imaging and magnetic hyperthermia applications

This PhD Thesis involves the development of a new synthetic protocol for iron oxide silica composite nanoparticles useful in MRI and magnetic hyperthermia. Our approximation combines the sol-gel chemistry and supercritical fluids to obtain biocompatible, spherical composite particles, with narrow particle size distribution. The composite particles showed very high values of relaxivity. We have also studied the dependence of the specific absorption rate with iron concentration. This manuscript is organized into seven chapters. Chapter 1 provides a general introduction to magnetic nanoparticles, their properties, synthesis, stabilization and applications, with special interest in the biomedical field. The aim of the chapter is to place the reader in the scientific context of the thesis. Chapter 2 describes the synthesis of nanoparticles by thermal decomposition of an iron complex, Fe(CO)5, and their characterization in solid and colloidal dispersion. Silica coating is a convenient approach to stabilize nanoparticles in a biocompatible way. In this thesis we have developed a new synthetic protocol to coat iron oxide nanoparticles with silica that combines the sol-gel chemistry and supercritical fluids. To understand and control the details of this procedure, we first synthesized nano- and microparticles of silica. They are described in Chapter 3. Chapter 4 includes the synthesis of the composite γ-Fe2O3@SiO2 nanoparticles. The core is composed of clustered iron oxide nanoparticles (described in Chapter 2) surrounded by a silica shell. Chapter 4 also describes the material characterization, with special emphasis on the magnetic properties, which will be exploited in the biomedical applications. We also succeeded in synthesizing composite ε-Fe2O3@SiO2 nanospheres from the previous γ-Fe2O3@SiO2 particles. The evaluation of the materials described in Chapters 2 and 4 as contrast agents for magnetic resonance imaging and as mediators for magnetic hyperthermia is included in Chapter 5. Chapter 6 lists the main conclusions derived from the present thesis. Finally, Chapter 7 gathers the annexes. It includes four publications arising from the main subject of this thesis, as well as five other publications and a patent on projects that I worked during the time that has lasted my doctoral thesis. The annexes also include a brief description of the experimental techniques used and protocols for sample preparation