Date of Award
12-2024
Document Type
Dissertation
Degree Name
Doctor of Philosophy (PhD)
Department
Chemical and Biomolecular Engineering
Committee Chair/Advisor
Jessica Larsen
Committee Member
Marc Birtwistle
Committee Member
Scott Husson
Committee Member
Angela Alexander Bryant
Abstract
This dissertation investigates the development and optimization of pathology-responsive polymersomes for simultaneous enhanced magnetic resonance imaging (MRI) and enzyme replacement therapy (ERT) in the treatment of GM1 gangliosidosis (GM1). While therapeutic strategies exist for similar, non-neuropathic lysosomal storage disorders, implementation towards GM1 faces significant challenges due to the blood-brain barrier.
Herein, we developed and characterized a range of low molecular weight hyaluronic acid-b-polylactic acid (HA-PLA) polymersomes (PSs) capable of encapsulating therapeutic enzymes in their hydrophilic core. These polymersomes exhibit pathophysiology-triggered responsiveness, degrading in the presence of acidic conditions, which is characteristic of lysosomes, and enzymes such as hexosaminidase A, which is elevated as a compensatory result of GM1.
The work presented in this dissertation contributes to the advancement of nanotechnology-based theranostics, emphasizing the integration of diagnostic and therapeutic functions in a single, responsive system. Our findings open new avenues for the treatment of lysosomal storage disorders and other conditions requiring targeted delivery across the blood-brain barrier.
Recommended Citation
Foster, Dorian, "Magnetic Resonance Imaging Trackable Pathology-Triggered Polymersomes Toward Enzyme Replacement Theranostics for GM1 Gangliosidosis" (2024). All Dissertations. 3839.
https://open.clemson.edu/all_dissertations/3839
Author ORCID Identifier
0000-0003-4452-1257
Included in
Biochemical and Biomolecular Engineering Commons, Enzymes and Coenzymes Commons, Nanomedicine Commons, Nanoscience and Nanotechnology Commons, Polymer Science Commons