Doctor of Philosophy (PhD)
The work presented in this dissertation employs nanomaterials derived from a group of uniform materials based on organic salts (GUMBOS) for selective chemotherapeutic applications. GUMBOS, similar to ionic liquids, are organic salts consisting of a bulky cationic and anionic moiety. In contrast to ionic liquids, these materials have melting points ranging from 25–250 °C, making them solid phase at room temperature. Similar to ionic liquids, GUMBOS display tunable properties, such as hydrophobicity and solubility, through counter ion variation. These tunable properties provide a variety of applications for these GUMBOS, including selective chemotherapeutics applications. The work in this dissertation evaluates the chemotherapeutic behavior of a series of nanomaterials, i.e, nanoGUMBOS, derived from rhodamine dyes to examine the role of both anion variation as well as cation structure on the therapeutic efficacy of the nanoparticle. Firstly, the mechanism of selective toxicity of previously investigated rhodamine 6G (R6G) nanoGUMBOS was determined. Interestingly, these R6G nanoGUMBOS displayed internalization via endocytosis in cancer cells while they lacked endocytic internalization in normal cells. This variation in internalization pathways ultimately resulted in the observed selective behavior of these R6G nanoGUMBOS. In my second project, the role of cyclodextrin (CD) templating on the size and selective chemotherapeutic behavior of these R6G nanoGUMBOS was evaluated. These CD-templated nanoGUMBOS displayed a remarkable two to three-fold increase in toxicity with no effect on selectivity. In my latter two chapters, the therapeutic efficacy of nanoGUMBOS derived from various rhodamine dyes is examined to assess the role of cation structure on selective chemotherapeutic behavior. Intriguingly, a significant difference was found in the selective behavior of GUMBOS derived from ester and carboxylic acid derivatives. In this regard, nanoGUMBOS derived from ester derivatives displayed selective chemotherapeutics toxicity similar to that of R6G nanoGUMBOS. In contrast, GUMBOS derived from carboxylic acid rhodamines displayed non-selective behavior, suggesting that the selectivity was structure dependent. Further examination of a triple nanoGUMBOS structure corroborated these results as modification of the carboxylic acid structure led to complete selectivity of these nanoGUMBOS under examined conditions. Moreover, these studies demonstrate the promising therapeutic potential and advantages of rhodamine based nanoGUMBOS for selective chemotherapeutic applications.
Bhattarai, Nimisha, "Chemotherapeutic Applications of Rhodamine Based NanoGUMBOS" (2018). LSU Doctoral Dissertations. 4499.
Available for download on Saturday, March 02, 2019