Thesis
Lysozyme-encapsulated gold nanoclusters as a potential therapy for Alzheimer’s disease
- Creator
- Rights statement
- Awarding institution
- University of Strathclyde
- Date of award
- 2025
- Thesis identifier
- T17413
- Person Identifier (Local)
- 202266199
- Qualification Level
- Qualification Name
- Department, School or Faculty
- Abstract
- Background: Alzheimer's disease (AD), the most common cause of dementia, is characterised by synaptic loss and neurodegeneration. Amyloid-β (Aβ) accumulation into plaques, hyperphosphorylation of tau protein, and neurofibrillary tangles (NFTs) in the brain are considered the pathological hallmarks of AD. However, more recent evidence suggests that neuroinflammation plays a key role in the pathophysiology of AD and causes dysregulated cellular activity and neurodegeneration by over-activating microglia. Novel lysozymeencapsulated gold nanoclusters have immunomodulatory roles like inhibiting the formation Aβ plaques via the modulation of immune responses mediated by microglial cells and can therefore be used as a new therapy for AD. Hypothesis: Lysozyme-encapsulated gold nanoclusters (Lys-AuNCs) influence AD pathology through modulating immune responses mediated by microglial cells and hence may be used as a therapy for AD. Methodology: Lys-AuNCs were synthesised using a modified ‘one-pot process’ adding filtration to account for sterile cell culture. Lys-AuNCs were characterised through fluorescent lifetime measurements with concentrations calculated from calibration curves to ensure physiochemical and optical propertiesremained intact. Activation of microglial cell line HMC3 by Lys-AuNCs was confirmed by positive staining with microglia marker IBA-1, then microglial phenotype was investigated through cell morphological analysis via phase imaging. Toxicity of Lys-AuNCs on HMC3s was determined via MTT assay. Localisation of LysAuNCs were visualised via z-stack imaging of HMC3 cells. Pro- and anti-inflammatory markers iNOS and Arg-1 expression induced by Lys-AuNCs were assessed through staining and quantified using ImageJ software. Results: HMC3 cells displayed resting morphology when treated with concentrations of LysAuNCs ranging from 50-600 μg/mL with some cells displaying activated morphology at 200 μg/mL. Lys-AuNCs induced a slight decrease in viability in HMC3 cells at 600 μg/mL after 72 hours (-88.9%;*p<0.05) compared to untreated cells, with no significant decrease in viability across other concentrations. HMC3 cells treated with 10 μg/mL of Lys-AuNCs showed an increase in iNOS expression with no significant changes seen in other concentrations (5, 50 and 200 μg/mL) (**p<0.01). Treated cells showed a significant reduction in Arg-1 expression across all concentrations (5, 10, 50 and 200 μg/mL) (****p<0.0001). Cells treated with 50 and 200 μg/mL of Lys-AuNCs showed intracellular localisation of clusters in HMC3 cells with staining and confocal imaging. Conclusions: Results showed that Lys-AuNCs induced minimal toxicity in HMC3 cellstreated with 600 μg/ mL after 72 hours and no toxicity in all other concentrations. It can be confirmed that Lys-AuNCs can activate and modulate the immune response of microglial cells with morphology changes and marked pro-inflammatory mediator expression thus, targeting microglia should be further investigated as it may provide a potential effective therapy against AD.
- Advisor / supervisor
- Jiang, Hui-Rong
- Resource Type
- DOI
- Embargo Note
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File | 2025-07-30 | Private |