NANOPARTICLE-BASED CONTRAST AGENTS FOR CT IMAGING, INFLAMMATORY BOWEL DISEASE, AND OTHER BIOMEDICAL APPLICATIONS

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Degree type
Doctor of Philosophy (PhD)
Graduate group
Biochemistry and Molecular Biophysics
Discipline
Engineering
Subject
Cerium
Contrast agent
CT
Drug delivery
IBD
Nanoparticles
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2024
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Author
Rosario Berrios, Derick
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Abstract

This thesis addresses the challenge of enhancing computed tomography (CT) imaging, particularly for inflammatory bowel disease (IBD), by developing novel nanoparticle-based contrast agents. The research focuses on the limitations of traditional iodinated contrast agents and investigates the potential of nanoparticles to provide superior imaging and therapeutic capabilities. To tackle this problem, the study first explores the advancements in spectral photon counting CT (SPCCT) technology and compares traditional contrast agents with innovative nanoparticle-based agents. PEGylated gold nanoparticles (AuNPs) with core sizes ranging from 5 to 75 nm were synthesized and characterized to assess their impact on gastrointestinal tract imaging in IBD. Despite expectations of size-dependent behavior, the results revealed minimal effect of nanoparticle size on agent progression through the GI tract but demonstrated significantly enhanced contrast and near-total clearance within 24 hours, suggesting promising clinical utility. Additionally, the study develops dextran-coated cerium oxide nanoparticles (Dex-CeNP) as a dual-function agent for both imaging and therapy. The Dex-CeNP, particularly the 5 kDa formulation, showed strong CT contrast, high X-ray attenuation, and superior biocompatibility in vitro. In vivo studies using a DSS-induced colitis mouse model highlighted the enhanced gastrointestinal contrast and prolonged retention at inflammation sites, along with anti-inflammatory properties and effective regulation of TNF-α levels. The conclusions drawn from this investigation underscore the efficacy of nanoparticle-based contrast agents in improving CT imaging and therapy for IBD. The findings pave the way for the broader application of these agents in biomedical imaging and treatment, offering significant advancements over current diagnostic and therapeutic approaches.

Advisor
Cormode, David, P.
Date of degree
2024
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