Magnetic Resonance Imaging Trackable Pathology-Triggered Polymersomes Toward Enzyme Replacement Theranostics for GM1 Gangliosidosis

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.