Date of Award

Spring 5-2021

Degree Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

School

Polymer Science and Engineering

Committee Chair

Sarah Morgan

Committee Chair School

Polymer Science and Engineering

Committee Member 2

Xiaodan Gu

Committee Member 2 School

Polymer Science and Engineering

Committee Member 3

Sergei Nazarenko

Committee Member 3 School

Polymer Science and Engineering

Committee Member 4

Robert Lochhead

Committee Member 4 School

Polymer Science and Engineering

Committee Member 5

Charles Scales

Abstract

This dissertation focuses on the development of a range of bioinspired polyelectrolytes with controlled architectures for gene and drug delivery applications. Glycans are ubiquitous in biological systems, and understanding the role of saccharide stereochemistry, as well as cationic charge, on polymer behavior in aqueous solution and the interactions with nucleic acids can provide insight into how synthetic polyelectrolytes can be used for non-viral gene delivery and other biological applications. The first chapter provides an introductory overview on how cationic polyelectrolytes can be used to aid the delivery of RNA for controlling gene expression in a variety of cell types, how molecular dynamics can be used to simulate the interactions between the cationic polyelectrolytes and RNA, and finally how pH-responsive hydrogels can be used to facilitate drug delivery for a range of biomedical applications. In the second chapter, the synthesis of cationic glycopolyelectrolytes for RNA interference in tick cells is presented, where the polymers are functionalized with either glucose or galactose pendant groups as well as tertiary amine pendant groups. The saccharide stereochemistry is shown to influence the intermolecular interactions between the glycopolyelectrolytes and double-stranded RNA (dsRNA), which ultimately causes differences in the relative expression of SelenoK transcripts within the tick cells. In the third chapter, molecular dynamics simulations are conducted to further understand the role of saccharide structure on the dynamics of glycomonomers and cationic oligomers in aqueous solution. Glucose- and galactose-functionalized monomers and oligomers are observed to have different intermolecular hydrogen bonding behavior in solution, which influence glycopolymer interchain interactions and their interactions with dsRNA. In the fourth chapter, characterization of anionic multilayer hydrogels by atomic force microscopy nanoindentation is discussed. The surface morphology and modulus of pH- responsive multilayer hydrogel networks prepared by layer-by-layer assembly are shown to be highly influenced by fabrication conditions, which includes polymer deposition method (dip-coating or spin-coating) and sacrificial layer polymer molecular weight.

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