Exploring the Potential Use of Porous Silica Nanoparticles in CEST-MRI

Abstract

Magnetic resonance imaging (MRI) is a widely used modality in diagnostics, treatment, and monitoring various conditions due to its ability to generate high-resolution images using non-ionizing radiation. The advent of contrast agents, which generally work by increasing the spin relaxation rate constants of water protons, has led to image enhancement. Despite the usefulness of this class of agents in diagnostic medicine, their inability to provide in-depth functional and anatomical information, coupled with their high detection limits, has led to new agents being explored. Chemical exchange saturation transfer (CEST) presents an alternative route to generate signals via repetitive saturations transfers between small molecules and bulk water, thus amplifying the signal and making it possible to detect small concentrations. Encapsulating a paramagnetic chemical shift agent in a nanoparticle with a large amount of water allows for simultaneous selective saturation of a large number of water protons. When these protons are allowed to exchange with bulk water protons in a controlled manner, the sensitivity improves, lowering the detection limit. Still, the small number of exchanging protons on these CEST agents means the problem of high detection limits persists. In this thesis project, the goals were to establish synthetic access to two types of mesoporous silica nanoparticles with different internal morphologies and determine whether a solid silica coating can effectively encapsulate charged paramagnetic contrast agents within the interiors of the mesoporous silica nanoparticles. Mesoporous silica nanoparticles (MSNs) were developed following a modified literature procedure. Details of how the incorporation of two swelling agents (including one not reported previously) is also presented. The viability of synthesizing the MSNs with and without the swelling agents was also assessed, and reasons for observed variations were discussed. Hollow mesoporous silica nanoparticles (hMSN) were also synthesized using a modified literature-based method which generally includes three steps: solid core synthesis, mesoporous shell deposition, and etching. A delayed-addition Stöber-based procedure for synthesizing the templating silica is also presented, improving size consistency from batch to batch. With evidence of solid silica being porous to water, both types of nanoparticles were solid silica-coated to effectively trap the load inside. An easily detectable surrogate dye with the same charge as the intended load was used for the studies. Several techniques were used to quantify surface silanol, assess amine functionalization, and evaluate the effectiveness of the coating procedure.