Date of Award
Doctor of Philosophy
Brian G. Trewyn
This thesis dissertation presents the collective research into the advancement of mesoporous silicate particles as biointerface devices, the development of new materials and the application of
these particles as solid supports for heterogeneous catalysis.
Mesoporous silica has been utilized in the aforementioned applications due to several reasons; the first being the ability to achieve high surface areas (500 - 1000 m2 g-1) with controlled
pore sizes and particle morphology. Another reason for their popularity is their robustness in applications of heterogeneous catalysis and the ability to functionalize the surface with a wide variety of organic functional groups. In the field of biointerface devices, mesoporous silica nanoparticles represent a class of materials that exhibit high biocompatibility. In addition, the ability to
functionalize the surfaces (outer surface and pore interiors) allows the particles to be targeted to specific cell types as well as the ability to release many different therapeutic molecules under specific stimuli.
A unique particle coating consisting of a chemically cleavable lipid bilayer that allows for the encapsulation of a fluorescent molecule and increases the biocompatibility of the particle has been
developed. The lipid bilayer coated mesoporous silica nanoparticle (LB-MSN) was characterized using X-ray diffraction, transmission electron microscopy and nitrogen `sorption isotherms. The
finished LB-MSN was then incubated with mammalian cells in order to prove their biocompatibility. Confocal micrographs demonstrate the endocytosis of the particles into the cells. In addition the micrographs also show that the LB-MSNs are separate from the endosomal compartments, however due to the lipophilic nature of the dye used to label the endosome there is some debate regarding this conclusion. The lipid bilayer coating was then applied to a large pore MSN (l-MSN) which had been
previously shown to cause lysis of red blood cells (RBCs) at low concentrations of particles. The lipid bilayer allowed the particle to interface with particle without resulting in haemolysis. It was observed however, that spiculation (damage) of the RBCs still occurred despite the lack of cell lysis. During the course of the study, the composition of the outer leaflet of the lipid bilayer was altered to more closely match that of the outer leaflet of RBCs. This alteration proved to make the LB-l-MSN particle extremely compatible with RBCs in that spiculation of the cells was reduced by more than 50 % according to observations by scanning electron microscopy.
A new synthetic route to mesoporous silica nanoparticles (MSNs) was developed using water in oil (W/O) emulsions was developed. This method relies on the presence of an amphiphilic
stabilizer molecule to control the size and quality of the spherical morphology of the particles. Partitioning of the oil phase into cetyltrimethylammonium bromide surfactant molecules is implicated in expanding the size of the mesopores from the standard 3 nm pore to 7 nm. This material is extensively characterized using X-ray diffraction techniques and TEM microscopy. Chapter 3 also outlines the synthesis of a new periodic mesoporous organosilica (PMO) in which the bridging
organic group is a benzobisoxazole molecule synthesized in the research group of Dr. Malika Jeffries-EL. While no immediate application of this new particle was proven, we propose this structure as the basis for a new class of light harvesting or light emitting diode material based on the performance of
the polymers containing these benzobisoxazole moieties and functionalized dyes.
The final project was the initial development of an N-heterocyclic carbene ligand based on an imidazole framework. This project represents significant synthetic challenges in that the pattern of
substitution on the imidazole framework has not been reported in the literature to the best of our knowledge. Despite the synthetic challenges, significant progress has been made towards the goal of generating an MSN with a functional group capable of coordinating a wide variety of metals for an extensive array of catalytic reactions. Additionally, N-heterocyclic carbenes have been shown to have anti-bacterial and anti-tumor capabilities. We propose that these new ligands may also represent a
significant advancement in the field of biomedical applications of MSNs.
Robert Anthony Roggers
Roggers, Robert Anthony, "Mesoporous Silicates: Materials Science and Biologica Applications" (2012). Graduate Theses and Dissertations. 12630.