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Title: Microbubble adhesion to healthy and diseased vascular cells : the role of surface charge
Author: Ja'Afar, Fairuzeta
ISNI:       0000 0004 6348 1075
Awarding Body: Imperial College London
Current Institution: Imperial College London
Date of Award: 2015
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Medical ultrasound (US) imaging is an established and powerful tool for diagnostic imaging. Combined with contrast enhancing agents called microbubbles, its imaging performance has been improved, as well as offering a potential tool for molecular imaging and targeted drug delivery and therapeutics. Microbubbles (MBs) consist of micron-sized, inert gas cores stabilised by a lipid monolayer or protein and suspended in aqueous dispersion. These non-targeted blood perfusion agents were found to persist in circulation, sticking to sites of inflammation or injury in the vasculature. This non-targeted MB retention in the vasculature is not fully understood and this project investigates the role of surface charge on MB-cellular adhesive behaviour. The adhesion of current clinical MBs, SonoVue™, Definity™, Optison™, and an experimental agent, BR38, with healthy and diseased vascular phantoms were observed in vitro. Human umbilical vein endothelial cells (HUVECs) were used to mimic the healthy vasculature and TNFα-activated HUVECs mimicked the diseased vasculature. Some degree of preferential binding for the TNFα-activated versus non-activated HUVECs was observed, indicating a surface component to this interaction. We hypothesised that surface charge plays a role in this interaction. MB surface charge was characterised with laser Doppler electrophoresis (LDE), the most widely-used method for determining particle surface charge. However, MB buoyancy compromised the reliability of this method and hence a micro-electrophoretic technique to determine MB surface charge was developed. MB electrophoretic movement was tracked using an in-house algorithm which was able to determine MB surface charge with at least a 10-fold improvement in relative standard deviations when compared to the LDE method. Our findings suggest an electrostatic role in MB adhesion to TNFα-activated HUVECs for phospholipid-stabilised MBs but not for protein-stabilised MBs. In conclusion, while surface charge may play a role in MB adhesion, there may be other unknown factors which can contribute to MB-cellular interaction.
Supervisor: Seddon, John M. ; Tang, Mengxing ; Leen, Edward Sponsor: Ministry of Education ; Brunei
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral