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.

Author ORCID Identifier

0000-0003-4452-1257

Available for download on Wednesday, December 31, 2025

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