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Dexamethasone Conjugated Iron Oxide Nanoparticles as a Theranostic Platform for Inflammation Imaging & Corticosteroid Delivery

Seitz, Taylor
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Abstract
Effective treatment of inflammation is hindered by limitations in corticosteroid delivery and the inability to simultaneously monitor therapeutic response. Interpolymer-complexed superparamagnetic iron oxide nanoparticles (IPC-SPIOS) were formed through hydrogen bonding between polygallol and polyethylene glycol (PEG) coated iron nanoparticles. This polymer complex has limited water access to their magnetic core and suppressed MR contrast in an inactivated state. We expanded on this work by incorporating dexamethasone (DEX) via conjugation to PEG through a reactive oxygen species (ROS)-cleavable thiodiacetic acid linker, enabling simultaneous diagnostic imaging and targeted drug delivery; a theranostic approach to inflammation management. DEX-PEG conjugates were synthesized through multiple steps, including an aqueous workup, column chromatography, and thin layer chromatography (TLC). ROS-triggered release profiles were quantified using a DEX-sensitive ELISA assay under hydrogen peroxide and enzymatically generated superoxide conditions. MR activity was evaluated to confirm contrast activity in environments with oxidative stress. In vitro studies utilized RAW 264.7 macrophages to test nanoparticle cytotoxicity and attenuation of inflammatory signaling pathways (TNF- ? & IL-6) via quantitative polymerase chain reaction (qPCR). Finally, NF-??B reporter macrophages were used to assess inflammatory pathway activation following LPS stimulation. NMR and TLC visualization of the conjugate confirmed the successful incorporation of the drug polymer complex. ROS-triggered release studies demonstrated concentration of dependent drug liberation, consistent with oxidative linker cleavage mediated release. MR contrast switching was confirmed between inactivated and ROS activated state. Finally, in vitro studies demonstrated biocompatibility consistent with ISO standards and measurable suppression of transcriptional activity related to inflammation in DEX-loaded nanoparticles. NF-??B reporter macrophages also demonstrated reduced pathway activation following treatment. These results establish a ROS-responsive IPC-SPIO theranostic platform that combines MR based disease monitoring with localized, inflammation activated corticosteroid delivery. Collectively, our findings demonstrate promise as a spatiotemporally controlled strategy for treatment and diagnosis of inflammatory conditions.
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Date
1/1/2026
Student Status
Junior (Graduating in 2027)
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Program/Major
Biomedical Engineering
College/School
College of Engineering and Mathematical Sciences
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Engineering
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