- Title
- Targeting reactive oxygen species in virus-induced airways disease
- Creator
- Adams, Thomas J.
- Relation
- University of Newcastle Research Higher Degree Thesis
- Resource Type
- thesis
- Date
- 2025
- Description
- Research Doctorate - Doctor of Philosophy (PhD)
- Description
- The immune response to virus infection in the respiratory tract must be carefully balanced to achieve pathogen clearance without undue immunopathology. For chronic respiratory diseases where there is ongoing inflammation, such as in asthma and chronic obstructive pulmonary disease (COPD), airway immune balance is disturbed, and respiratory virus infection frequently exacerbates disease. Reactive oxygen species (ROS) are critical to induction and propagation of inflammation. When appropriately regulated, ROS are vital cell signalling molecules and contribute to innate immunity. However, extended periods of high ROS concentration can cause excessive cellular damage that dysregulates anti-viral immunity and promotes inflammation. Traditional antioxidant therapeutics have had limited success treating inflammatory diseases such as viral exacerbations of asthma or COPD owing to non-specific pharmacology and poorly understood pharmacokinetic properties. These drawbacks could be addressed with novel drug delivery technologies and pharmacological agents. I hypothesised that targeted delivery of mitochondrial antioxidants to epithelial cells would modulate their immune response to rhinovirus (RV) infection, demonstrating the potential of a novel therapeutic approach. In this thesis, I first optimised a targeted nanoparticle formulation for effective delivery of a mitochondrial antioxidant, MitoTEMPO (MiT) to produce a targeted antioxidant nanomedicine (TNM). I then developed a fluorescence-based assay to detect mitochondrial ROS (mtROS) directly in live epithelial cells before using it to verify that RV infection induced mtROS production could be potently attenuated with TNM treatment. Using an in-vitro air-liquid interface (ALI) model of bronchial epithelial cells, the pharmacological response to TNM treatment was further investigated.
- Subject
- respiratory medicine; reactive oxygen species; nanoparticle; mitochondrial antioxidant; COPD; rhinovirus; air-liquid interface; drug delivery
- Identifier
- http://hdl.handle.net/1959.13/1517907
- Identifier
- uon:57194
- Rights
- Copyright 2025 Thomas J. Adams
- Language
- eng
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