MESOPOROUS SILICA NANOPARTICLES AS DRUG DELIVERY SYSTEMS AND DIAGNOSTIC TOOLS
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Micro- and nano-scale silica materials have recently gained attention due to their potential as biosensors, site-specific drug delivery systems and diagnostic tools. Accordingly, examples of the preparation and use of silica materials for such applications are highlighted throughout this dissertation. A significant portion of developing materials used for targeting, detection, or sensing applications is functionalizing the surface of the material with biomolecules (i.e. proteins, nucleotides, carbohydrates) that function as targeting or receptor moieties. N-linked pentenyl glycoside derivatives, prepared via a modified Staudinger ligation method, proved to be key intermediates in developing a methodology to efficiently prepare carbohydrate derivatives capable of functionalizing a variety of different materials. Glucosyl and lactosyl siloxane derivatives, synthesized from the hydrosilation of the corresponding pentenyl glycoside intermediate, were used to prepare glucose- and lactose-functionalized evanescent wave fiber Bragg gratings. The carbohydrate-functionalized fibers were subsequently used to detect the specific binding of lectins to the carbohydrates attached to the surface of the fiber, demonstrating their potential as biosensors. In addition, olefin cross metathesis was used to couple N-linked pentenyl glycoside intermediates with terminal alkene derivatives containing moieties used to functionalize a range of inorganic material, thus yielding glycoconjugates capable of functionalizing material of various composition. The advantage of this synthetic strategy is the ability to create a series of carbohydrate derivatives capable of functionalizing a variety of different material from a common N-linked pentenyl glycoside intermediate. Mesoporous silica nanoparticles (MSN) have potential as drug delivery and controlled release devices due to their high surface area and large payload capacity. The effect of surface charge and pH on the release of the fluorescent dye rhodamine 6G from MSN prepared via an aerosol methodology has been studied. Release profiles of rhodamine 6G from bare and amine-coated MSN at pH 5.0 and 7.4 are very different and demonstrate that electrostatic interactions between entrapped rhodamine 6G molecules and the charged surface of the MSN have a significant effect on release kinetics. Release of rhodamine 6G from amine-coated MSN can be fit to a single exponential function, while release from bare MSN can be fit to a double exponential function--indicating that the release of rhodamine 6G from bare MSN is a two-phase process. In addition, it was determined that MSN need to be sonicated in dye solution to maximize their loading capacity. Fluorescent silica nanoparticles (FSN) are being studied for their potential in diagnostic imaging techniques and immunoassays. Fluorescent silica nanoparticles were prepared by incorporating a hydrophobically modified dye into a mesoporous silica nanoparticle synthesis procedure. The MSN-based FSN do not leach dye and have strong, stable fluorescence that is 5 times more intense than that of CdSe quantum dots. For diagnostic applications, a method to selectively and covalently bind antibodies to the surface of the FSN was devised. It was found that the triblock copolymer, Pluronic F127, is effective in preventing nonspecific binding of proteins to FSN. Antibodies were selectively and covalently attached to FSN that were functionalized with a mixed PEG/epoxide coating in the presence of Pluronic F127.