Development of Multifunctional Silica Nanoparticles for Application as Biological Imaging and Delivery Agents

Recent years have seen the increasing application of nanomaterials across a variety of industries, due to their versatility and readily adaptable properties. To optimise the unique benefits of this class of materials, their further study and development is essential. The biomedical and health industries, in particular, have adapted to use nanomaterials and nanotechnologies from drug development and delivery to diagnostic technologies to the enhancement of therapeutic treatments. The readily tuned properties of nanomaterials including size, shape, composition and surface chemistry have distinguished them as materials with diverse, novel properties. Silica nanoparticles, especially, are a class of nanomaterial with manyfold attractions including their biocompatibility, their readily tuned physical features, their ability to carry a load both internally and on the nanoparticle surface and their stability in a wide range of environments. This work demonstrates the adaption of the renowned Stöber method to produce dense, spherical silica nanomaterials within the optimal cellular uptake range of 30 to 90 nm. It subsequently considers controlled functionalisation to both the surface and core of these nanoparticles to produce multifunctional systems which can be loaded with optically detectable materials, tracked throughout cellular uptake and decorated with complex surface molecules capable of multiple sensing and biorecognition events. The second chapter considers the design of the core nanoparticles, optimising the properties of nanoparticle size and internal loading with a range of cationic dyes. The relationship between size and dye loading is also explored through the encapsulation of a range of ruthenium polypyridyl complexes, porphyrin derivatives and organic dyes used in cellular imaging. The ability to tune the surface chemistry of these NPs with a range of new functional groups is also demonstrated, producing nanoparticles with increased chemical reactivity and new colloidal dispersion properties. The third chapter considers the addition of DNA intercalating groups via the functional handles established on the nanoparticle surface in the previous chapter. The ability to modify the surface of nanoparticles from 35 to 90 nm in diameter is demonstrated, with two different DNA intercalating molecules with strong optical properties. The ability to tune the emissive properties intercalator modified silica nanoparticles is approached through control over the surface loadings and through wavelength-dependent activation of monomeric and aggregate type surface bound molecules. The interactions of the surface bound DNA binding molecules is probed with a compatible host molecule, with the subsequent detection and quantification of non-covalently loaded surface materials. Finally, the DNA affinity of a range of silica nanoparticles is considered where features such as size, charge and surface chemistry are altered. In the fourth chapter, the Ugi multicomponent organic chemistry reaction is harnessed to produce branch-structured, co-functionalised silica nanoparticles through a mild, one-pot approach. This advanced surface modification gives access to highly functional nanoparticles with diverse optical properties, bio-recognition abilities and advanced sensing capabilities. Finally, in the fifth chapter the cellular uptake of these materials is studied. Nanoparticles with varying surface chemistry and core compositions are incubated with HeLa cells, determining the optimised group of NPs for uptake. In agreement with the literature, good biocompatibility of a range of these nanoparticles is demonstrated, with materials of approximately 50 nm in diameter showing the lowest toxicity.