Date of Award

Summer 2024

Document Type

Open Access Dissertation

Department

College of Pharmacy

First Advisor

Pisheng Xu

Abstract

Alzheimer's disease (AD) is a devastating neurodegenerative disorder that affects millions worldwide. Unfortunately, there are currently no effective therapies available to prevent or cure the disease. While current therapies aim to change AD progression, there is a growing need for novel therapeutic strategies that can effectively penetrate the blood-brain barrier (BBB) to target the underlying pathology of the disease. The BBB is a highly selective semipermeable barrier that separates circulating blood from the brain. It plays a crucial role in amyloid-β (Aβ) homeostasis and clearance dynamics, as Aβ accumulation is a key factor in the pathogenesis of AD. Aβ aggregation can lead to downstream effects such as neuroinflammation, oxidative stress, and synaptic dysfunction. The BBB also serves to protect the brain from harmful substances, including drugs. However, this barrier also prevents many potential AD therapies from effectively crossing into the brain, making it difficult to deliver therapeutic agents to the site of action. To overcome this challenge, we have developed a brain-targeted ceria nanoparticle (CeNP) system called RAGE-CeNP@ET@APF. This system incorporates apoferritin (APF), a natural iron storage protein that enhances the biocompatibility and penetration of CeNPs into the BBB via interaction with transferrin receptor 1 (TfR1), a receptor highly expressed in brain endothelial cells. RAGE, a multiligand receptor in the immunoglobulin superfamily, is also covalently conjugated on the surface of the nanoparticle system to facilitate penetration into the BBB and transport Aβ to the brain.

Rights

© 2024, Shanshan Shi

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