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Lysozyme-encapsulated gold nanoclusters as a potential therapy for Alzheimer’s disease

Student thesis: Master's Thesis

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
Date of Award12 Jun 2025
Original languageEnglish
Awarding Institution
  • University Of Strathclyde
SponsorsUniversity of Strathclyde
SupervisorHui-Rong Jiang (Supervisor) & Yu Chen (Supervisor)

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