Development and Applications of Fluorescent Core-Shell Silica Nanoparticles for Bioimaging and Sensing
Nano-sized fluorescent materials have demonstrated great potential in the emergent fields of nanobiotechnology and nanomedicine. To create effective probes for these applications, high brightness, photostability and size control are key parameters for particle design. Core-shell silica nanoparticles incorporating covalently bound dyes in the particle core have been shown to exhibit significant enhancements in dye brightness and photostability while allowing independent control of particle size, color and surface chemistry. Building on this platform, the first part of this dissertation explores a family of quantitative chemical sensors based on the incorporation of analyte-sensitive dyes into the particle shell. By co-localizing sensor and reference dye molecules onto a single particle, local analyte concentration changes can be discerned from local sensor concentration variations by comparison of the sensor and reference intensities facilitating quantitative ratiometric chemical imaging. The core-shell architecture is ideal for this application because it sequesters the reference dye in the particle core, while allowing analyte interactions with the sensor dyes near the particle surface. Traditional Stober-derived sol-gel routes as well as reverse micelle-based methods were employed to generate pH- and Ca+2-sensitive nanoparticles. Specific sensor architectures were applied to intracellular as well as large-scale functional volumetric imaging of intact biofilms and their metabolic activities. To fully realize the potential of fluorescent nanomaterials for biomedical applications, one of the key obstacles is clearance from the body. The second part of this dissertation investigates several of the key parameters for effective clearance (size and surface chemistry) and highlights the development of a series of particles capable of rapid and efficient bodily clearance and demonstrates their efficacy in mice as a model system.
nanoparticles; fluorescence; silica; biology
dissertation or thesis