2013 77 Ana Arizaga Páez Synthesis of core-shell magnetic nanoparticles for biomedical applications Departamento Física de la Materia Condensada Director/es Millán Escolano, Ángel Palacio Parada, Fernando Tesis Doctoral Autor Director/es UNIVERSIDAD DE ZARAGOZA Repositorio de la Universidad de Zaragoza – Zaguan http://zaguan.unizar.es Departamento Director/es Tesis Doctoral SYNTHESIS OF CORE-SHELL MAGNETIC NANOPARTICLES FOR BIOMEDICAL APPLICATIONS Autor Ana Arizaga Páez Director/es Millán Escolano, Ángel Palacio Parada, Fernando UNIVERSIDAD DE ZARAGOZA Física de la Materia Condensada 2013 Repositorio de la Universidad de Zaragoza – Zaguan http://zaguan.unizar.es Departamento Director/es Tesis Doctoral Autor Director/es UNIVERSIDAD DE ZARAGOZA Repositorio de la Universidad de Zaragoza – Zaguan http://zaguan.unizar.es Synthesis of Core-Shell Magnetic Nanoparticles for Biomedical Applications Synthesis of Core-Shell Magnetic Nanoparticles for Biomedical Applications Ana Arizaga Páez A Jose Luís y Ainhoa Index Preface.....................................................................................................1 1 Introduction and goals...........................................................................3 1.1 Advantages of MNPs in biomedical uses..........................................3 1.1.1 Magnetic resonance imaging (MRI)........................................6 1.1.2 Magnetic hyperthermia............................................................7 1.1.3 Biosensors................................................................................8 1.1.4 Drug delivery...........................................................................8 1.1.5 Targeting..................................................................................9 1.2 Magnetic properties of nanoparticles...............................................10 1.2.1 Superparamagnetism..............................................................12 1.2.2 Magnetic relaxation................................................................14 1.2.3 Specific absorption rate (SAR)..............................................15 1.2.4 Surface effects........................................................................16 1.3 Core-Shell structures of MNPs used in medicine............................16 1.3.1 Materials for the core.............................................................18 1.3.1.1 Iron oxides: An introduction........................................19 1.3.1.2 Synthesis of iron oxide MNPs......................................21 1.3.1.3 Strategies for the control of size in nanoparticles........25 1.3.2 Materials for the shell.............................................................26 1.3.2.1 Organic coatings...........................................................27 1.3.2.2 Inorganic coatings........................................................32 viii Index 1.4 Purpose of the thesis and goals........................................................35 1.4.1 Ferrofluids for biomedical applications.................................35 1.4.2 Superparamagnetic beads for a biosensor..............................36 1.4.3 MNPs encapsulated in a polymer for drug delivery...............37 1.5 Bibliography....................................................................................38 2 Experimental and methods..................................................................49 2.1 Introduction......................................................................................49 2.2 Experimental....................................................................................49 2.2.1 A survey of methods for the production of ferrofluids in organic media.....................................................................50 2.2.2 Synthesis of IOMNPs in organic solvents by thermal decomposition of Fe(CO) .....................................................53 5 2.2.2.1 Procedure for the synthesis of organic nanoparticle suspensions............................................................................55 2.2.3 Ferrofluids in aqueous media.................................................57 2.2.4 Procedure for the synthesis of aqueous MNPs suspensions...61 2.3 Methods...........................................................................................61 2.3.1 Chemical analysis..................................................................61 2.3.1.1 Titration........................................................................61 2.3.1.2 Thermogravimetric analysis.........................................63 2.3.1.3 Gel permeation chromatography..................................63 2.3.1.4 1H-NMR.......................................................................64 2.3.2 Structural characterization.....................................................65 2.3.2.1 Fourier transform infrared spectroscopy (FTIR)..........65 2.3.2.2 X-ray diffraction (XRD)...............................................66 2.3.2.3 Dynamic light scattering (DLS)...................................67 2.3.2.4 Transmission electron microscopy (TEM) ..................68 2.3.3 Magnetic characterization......................................................69 2.3.3.1 Magnetic characterization SQUID...............................69 2.3.3.2 SAR..............................................................................70 Index ix 2.4 Characteristics of the organic MNPs suspensions...........................70 2.5 Magnetic properties of the organic MNPs suspensions...................76 2.6 Magnetothermic properties of the organic MNPs suspensions........78 2.7 Characteristics of aqueous prepared ferrofluids...............................82 2.8 Bibliography....................................................................................85 3 Core-Shell ferrofluids for biomedical applications...........................87 3.1 Introduction......................................................................................87 3.1.1 Transferring nanoparticles from organic to aqueous media...89 3.1.2 Use of silanes for particle coating and redispersion in water.91 3.1.3 Dispersing hydrophobic nanoparticles in water by ligand exchange.................................................................................92 3.1.4 Our approach for the production of silica coated aqueous dispersions..............................................................................94 3.2 Experimental....................................................................................96 3.2.1 Synthesis................................................................................96 3.2.2 Physical and chemical characterization..................................97 3.3 Results..............................................................................................98 3.3.1 Use of short chain organosilanes with iron coordinating group......................................................................................98 3.3.1.1 Diethylphosphatoethyltriethoxysilane..........................98 3.3.1.2 N-(3-triethoxysilylpropyl)-4,5-dihydroimidazole......103 3.3.2 Use of long chain organosilanes with iron coordinating groups...................................................................................107 3.3.2.1 Magnetic properties....................................................110 3.4 Conclusions....................................................................................113 3.5 Bibliography..................................................................................115 4 Superparamagnetic beads for a biosensor.......................................123 4.1 Introduction....................................................................................123 4.2 Synthesis and characterization of superparamagnetic nanobeads..127