Due to their high surface area and size-dependent properties, nanoparticles have seen use as biomedical devices in the past several decades. Magnetic nanoparticles are of particular interest as their properties allow for a variety of uses including separations, targeting, imaging, and therapy. The biological milieu is not a pristine environment, however. The complex medium presents many challenges for particle stability and reproducible performance. It even makes fundamental particle characterization more difficult. In this thesis, magnetic iron oxide nanoparticles are investigated as biomedical devices which provide diagnosis/imaging and therapy (theranostics). Innovative methods for characterizing these particles and observing their behavior over time in biologically relevant environments are also presented. Overall, this thesis aims to make the important point that magnetic nanoparticles are not stagnant objects but are in fact dynamic systems capable of vast changes upon exposure to in vitro or in vivo environments. Aggregation, oxidation, and dissolution all play a role in real-world nanoparticle performance. To mitigate and control some of these concerns, a functionalized mesoporous silica shell is employed as a protective layer around the iron oxide nanoparticle cores. This protective shell causes resistance to each of the above-mentioned factors, resulting in more stable and predictable performance appropriate for treatment planning and biological use. In chapter one, various methods for the characterization of magnetic nanoparticles in biological matrices are reviewed. Several case studies are presented to demonstrate the necessity for complementary techniques to obtain a complete picture of nanoparticle transformations. In chapter two, an early-phase iron oxide/mesoporous silica core/shell nanoparticle is presented, and the effects of synthetic parameters and long term storage conditions on particle performance are examined. In chapter three, a commercially-available iron oxide nanoparticle is studied in detail in various biological environments to understand how particle heating and imaging properties are related and how aggregation can affect them. In chapter four, a functionalized mesoporous silica shell is applied to the iron oxide core from chapter three. The new core/shell particle demonstrates a substantial reduction in aggregation and thus a stabilization of material properties in vitro and in vivo. Finally, chapter five details a variety of transmission electron microscopy (TEM) studies with a focus on visualizing the nano/bio interface in vitro. Dark field TEM is presented as a useful tool for locating and differentiating inorganic nanoparticles, including but not limited to iron oxide nanoparticles, from biological structures or stain artifacts.
University of Minnesota Ph.D. dissertation. August 2015. Major: Chemistry. Advisor: Christy Haynes. 1 computer file (PDF); xvi, 191 pages.
The Power of Rust and Sand at the Nanoscale: Iron Oxide and Mesoporous Silica Nanoparticles for Biomedical Applications.
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