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Investigating the Accumulation, Sub-Organ Distribution, And Biochemical Effects of Nanomaterials Using Mass Spectrometry
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Abstract
Gold nanoparticles (AuNPs) are attractive materials for use in various biomedical applications, such as therapeutic delivery, due to their unique chemical properties and modular tunability. Mass spectrometry methods, including laser desorption/ionization mass spectrometry (LDI-MS) and inductively coupled plasma mass spectrometry (ICP-MS) have been successfully used to evaluate the distribution of AuNPs in complex biological systems. As new AuNP-based materials are developed for applications in therapeutic delivery, it is essential to simultaneously develop analytical techniques that can comprehensively assess their behavior in vivo. In this dissertation, novel mass spectrometric methods have been developed and utilized to evaluate the uptake, distribution, and biochemical effects of AuNPs and AuNP-based delivery materials. First, a dual-mode mass spectrometry imaging method was developed to 1) track the distribution of inorganic nanodelivery vehicles containing a deliverable therapeutic and 2) correlate the distribution of the subsequent biochemical effects with the carrier when injected into mice. Next, the correlation of the distribution of the inorganic carrier and biochemical effects were examined and quantified for specific sub-organ regions of tissues. These predicted changes were further evaluated for their biochemical relevance. Additionally, unexpected biochemical changes were evaluated by injecting mice with nanodelivery vehicles lacking an active therapeutic. Finally, a MS method was developed to quantitatively assess NP uptake into various cell types.
Type
dissertation
Date
2020-12