Mathieu Chastellain
The present thesis report deals about the material scientists contribution to the interdisciplinary European project "MAGNANOMED" involving people having very different backgrounds (physicist, chemists, biochemists, veterinary surgeons, ...). The work carried out was aimed at the development of iron oxide based nanoscale superparamagnetic composite particles for biomedical applications. Particles showing a superparamagnetic behaviour are of particular interest as they are sensitive to magnetic fields without retaining magnetisation after removal of the latter. Not only superparamagnetic particles can be guided, but they also exhibit heating properties when submitted to appropriate alternating magnetic fields. These characteristics make them promising for targeted applications where they could act as careers as well as activators. The local temperature increase can be used for confined control release of linked entities or to modify specific cells activities in a well defined area. Moreover iron oxide nanoparticles can be used for magnetic resonance imaging enhancement. No single sample could meet the requirements imposed by every application mentioned above, so the chosen strategy was first to synthesize and thoroughly characterize iron oxide nanoparticles. In a second step, the particles would serve as primary building blocks for higher order composite structures or "beads" (with one or more iron oxide cores) to be formed according to the specific needs of every particular application. The surface tailoring, so that to ensure the desired properties in physiological media and allow further functionalisation, consisted in an important part of the work. Despite the many works carried out in the field over the past decades, the needs for well controlled biocompatible superparamagnetic beads are not only important but also growing. A focus was made on three specific applications: hyperthermia (controlled heating in a well defined body area by means of an external alternating magnetic field), drug delivery (magnetic targeted drug release) and DNA purification (magnetically driven separation in vitro). A supplementary application called ferrofluid actuated micro pump is also described as it turned out that a synthesis side product could be judiciously used in this field. The achievements realized allowed to define a reproducible and versatile synthesis route, which fulfils the above mentioned criteria as summarised in the following. Iron oxide particles, which physical properties could be well controlled, were shown to generate heat when submitted to an external magnetic field suitable for medical applications. The measured power dissipated could be successfully related to the particles and field characteristics using a theoretical approach and the tremendous influence of particles size distribution was highlighted. Polyvinyl alcohol coated iron oxide particles were produced for drug delivery. Biocompatibility was asserted based on both in vitro and in vivo experiments. The particles bio-distribution could be influenced by means of a constant magnetic field (magnet) and depending on the coating nature (presence of functional groups), the cellular uptake could be controlled. Silica beads with a homogeneous iron oxide particles space distribution were synthesised in view of DNA separation using a novel approach. The bead size could be adjusted in the 20 nanometres up to several microns range. Preliminary classical plasmid automated purification experiments revealed a competitive separation yield. These results are promising in view of the final targeted application in currently developed quicker automated processes. A highly concentrated iron oxide suspension (ferrofluid) showing suitable colloidal stability was successfully applied in micropumps actuated by means of a magnetically induced ferrofluid motion. The obtained pumping characteristics such as backpressure and flow rate were better then described in literature for similar devices using water based ferrofluids. AFM 3D-view of iron oxide particles coated with polyvinyl alcohol, average height 9 nm (left) and Stonehenge monument in Britain, heaviest stone 50 tons (right). "In its day, the construction of Stonehenge was an impressive engineering feat, requiring commitment, time and vast amounts of manual labour" [http://www.britannia.com/ history/h7.html] (see appendix 12.6). Nowadays, this remark still holds for Nano-stonehenge synthesis ...
EPFL2004
