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Title: Polymersome mediated intracellular delivery : a tool for research and treatment of infectious and inflammatory diseases
Author: Robertson, James
ISNI:       0000 0004 5364 6745
Awarding Body: University of Sheffield
Current Institution: University of Sheffield
Date of Award: 2014
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Neutrophils contain a destructive arsenal of toxic molecules that are used to kill invading microorganisms, but inappropriate neutrophil responses can lead to excessive tissue damage, or inefficient destruction of infectious pathogens. Controlling this balance is crucial to prevent chronic disease. Neutrophil apoptosis and clearance by macrophages is a key step in the resolution of inflammation, but excessive production of pro-inflammatory cytokines can prolong neutrophil survival and lead to inflammatory disease. In contrast, inefficient destruction of the bacterium Staphylococcus aureus is thought to play an important role in the progression and dissemination of Staphylococcus aureus bacteraemia. Neutrophil dysfunction in infectious or inflammatory diseases might be correctable using synthetic vectors to deliver antiinflammatory or antibacterial molecules intracellularly, but neutrophils have proven notoriously difficult cells to manipulate. In this thesis I explore the potential of PMPC-PDPA polymersomes as intracellular vectors for neutrophils. I investigate how the physical properties of polymersomes influence their internalisation and reveal that the size and shape of polymersomes has a big impact on the efficiency of cargo delivery. I go on to show that these vectors do not affect neutrophil viability and can successfully deliver a range of cargo into these cells. Finally I show that polymersomes can deliver antibiotics and anti-inflammatory compounds intracellularly to help promote inflammation resolution and clear Staphylococcus aureus infection.
Supervisor: Renshaw, Stephen ; Battaglia, Giuseppe Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available