Biomedical Applications of Magnetic Nanoparticles

Abstract

The thesis focuses on the specific design of multifunctional magnetic nano-carriers for different biomedical areas. Different shapes of core/shell bi-magnetic nanoparticle have been synthesized by seedmediated growth, and their structural and magnetic properties have been studied. The experimental results showed that core/shell nanoparticles have a higher specific absorption rate compared to the core ones. For drug delivery application, the surface of the magnetic nanoparticles is functionalized using different techniques (Diels-Alder reaction and layer-by-layer technique). More precisely, a novel bi-functional thermo-responsive system, which consists of core/shell bi-magnetic nanoparticles with furan surface functionality, is bonded with N-(2-Carboxyethyl)maleimide through Diels-Alder reaction. The chemotherapeutics doxorubicin is attached onto the surface of the nanocarriers, and a high loading efficiency of 92% is obtained. This system with high responsiveness to a high frequency external alternating magnetic field shows a very good therapeutic efficiency in hyperthermia and drug release at relatively low temperatures (50 °C). On the other hand, a switch-controlled drug release is realized by coating the core/shell bi-magnetic nanoparticle with a pH-and thermo-responsive polymer shell. Doxorubicin is loaded onto the surface of the last coating layer, and a high loading efficiency is obtained. The nano-carriers are characterized with FTIR, dynamic light scattering, Zeta potential, In vitro hyperthermia, and vibrating sample magnetometry. The in vitro drug release experiments confirm that a small amount of doxorubicin is released at body temperature and physiological pH, whereas a high drug release is obtained at acidic tumor pH under hyperthermia conditions (43 °C). The core/shell bi-magnetic nano-carriers facilitate controllable release of doxorubicin as effect of induced thermo-and pHresponsiveness of the polymer when are subjected to an high-frequency alternating magnetic field at acidic pH; thereby the drug release rate is controlled using on-off cycles of the applied field. iii KURZFASSUNG Diese Arbeit befasst sich mit der speziellen Gestaltung von multifunktionalen magnetischen Nanopartikeln für diverse biomedizinische Anwendungen. Verschiedene Formen der Kern/Schale-bimagnetischen Nanopartikel wurden durch die "seed-mediated growth" Methode synthetisiert, und die strukturellen und magnetischen Eigenschaften dieser Formen untersucht. Die Versuchsergebnisse haben gezeigt, dass die Kern/Schale-Nanopartikel eine höhere spezifische Energiea als reine Kern Partikel haben. Für die Drug Delivery Anwendung wird die Oberfläche der magnetischen Nanopartikel auf unterschiedlichen Wege (Diels-Alder-Reaktion und Layer-by-Layer-Verfahren) funktionalisiert. Dazu wurde an ein neuartiges bifunktionelles thermosensitives System, welches aus furanbeschichteten Kern/Schale bi-magnetischen Nanopartikel besteht, N-(2-Carboxyethyl) maleimid durch Diels-Alder Reaktion angebunden. Mit der Anbindung des chemotherapeutischen Doxoru...