Multifunctional nanomaterials for diagnostic and therapeutic applications

.................................................................................................................................................. i LIST OF PAPERS ....................................................................................................................................... iii TABLE OF CONTENTS ............................................................................................................................ xi 1 INTRODUCTION ................................................................................................................................ 1 1.1 MAGNETIC NANOMATERIALS ............................................................................................................ 2 1.1.1 Nanoparticles ........................................................................................................................... 2 1.1.1.1 Properties of magnetic nanoparticles ................................................................................................. 2 1.1.1.2 Synthesis of magnetic nanoparticles .................................................................................................. 5 1.1.2 Nanocomposites ....................................................................................................................... 7 1.2 BIOMEDICAL APPLICATIONS OF NANOMATERIALS .............................................................................. 8 1.2.1 Drug delivery systems .............................................................................................................. 8 1.2.2 Visualization .......................................................................................................................... 10 1.2.2.1 Magnetic Resonance Imaging ......................................................................................................... 10 1.2.2.2 Fluorescent visualization ................................................................................................................. 12 1.2.3 Biosensor applications ........................................................................................................... 14 1.2.4 Hyperthermia ......................................................................................................................... 15 1.2.5 Bio-manipulation ................................................................................................................... 16 1.2.6 Multifunctional nanoparticles in biomedicine ....................................................................... 17 1.3 OBJECTIVES ..................................................................................................................................... 18 2 EXPERIMENTAL ............................................................................................................................. 19 2.1 INORGANIC NANOPARTICLES ............................................................................................................ 19 2.1.1 Synthesis of magnetic nanoparticles ...................................................................................... 19 2.1.1.1 Superparamagnetic iron oxide nanoparticles ................................................................................... 19 2.1.1.2 Thermally blocked iron oxide nanoparticles ................................................................................... 20 2.1.1.3 Studies of nanoparticles formation .................................................................................................. 20 2.1.2 Surface modification of magnetic nanoparticles ................................................................... 20 2.1.2.1 PLLA coating of SPION ................................................................................................................. 20 2.1.2.2 Pluronic F127 modification of SPION and PLLA-coated SPION ................................................... 21 2.1.2.3 Antigen functionalization of thermally blocked nanoparticles ........................................................ 22 2.1.3 Synthesis of Quantum Dots .................................................................................................... 22 2.1.4 Synthesis of gold nanorods .................................................................................................... 23 2.2 MULTIFUNCTIONAL NANOPARTICLES ............................................................................................... 23 2.2.1 Synthesis of PLLA-mPEG and PLGA-PEG-NH2 copolymers ................................................ 23 2.2.2 Multifunctional nanoparticles preparation via emulsion ...................................................... 24 2.2.3 Drug loading to SPION and PLLA-coated SPION ................................................................ 25 2.3 FERROGEL ........................................................................................................................................ 25 2.4 NANOCOMPOSITES ........................................................................................................................... 26 2.5 CHARACTERIZATION ........................................................................................................................ 26 2.5.1 Size, morphology and composition analysis .......................................................................... 26 2.5.1 Drug release rate measurements ........................................................................................... 27 2.5.2 Static magnetic measurements and MRI evaluation .............................................................. 28 2.5.3 Magneto-optic measurements ................................................................................................ 28 2.5.4 Dynamic magnetic measurements ......................................................................................... 28 2.6 BIOSENSOR DEVELOPMENT .............................................................................................................. 29 3 RESULTS AND DISCUSSION ........................................................................................................ 31 3.1 SUPERPARAMAGNETIC IRON OXIDE NANOPARTICLES ....................................................................... 31 3.1.1 Morphology and structure studies ......................................................................................... 31 3.1.2 Magnetic studies .................................................................................................................... 31 3.2 THERMALLY BLOCKED IRON OXIDE NANOPARTICLES ....................................................................... 33