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Title: Studies on ultrasound-mediated cell membrane permeabilisation
Author: Li, Ying Suet
Awarding Body: University of Ulster
Current Institution: Ulster University
Date of Award: 2008
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Ultrasound, has conventionally been used in medical diagnostics and up until very recently its therapeutic use has been limited to use in physical therapy. More recently however, ultrasound has been recognised as offering significant potential in designing and developing various therapeutic strategies that would be based on the relative ease with which ultrasound can pass through living tissues. In this thesis I wished to explore the ability of ultrasound to facilitate membrane permeabilisation with a view towards maximising such an effect for possible therapeutic use in aiding the action of cancer chemotherapeutics so that site-specific or tissue targeted treatment strategies could be developed. In addition, I also wished to explore the possibility of optimising this ultrasound-stimulated phenomenon for possible use in gene transfer technology with a view towards its possible application in areas such as gene therapy. Indeed in this thesis, the preliminary studies consisted of examining the possibility of using ultrasound to enhance an existing method of gene transfer. : This latter aspect involved examining the positive impact of ultrasound on Lipofectamine-mediated gene transfer on a cellular target in vitro. In following on from those preliminary studies I employed fluorogenic marker compounds to study ultrasound-induced cell membrane 'poration' in vitro and using an optimised ultrasound exposure configuration I was able to optimise the ultrasound conditions required to facilitate high level membrane permeabilisation whilst retaining good cellular viability. Indeed these studies also, for the first time, demonstrated that superimposition of a high frequency pulse regime over a conventional ultrasonic field could enhance this membrane permeabilising effect in the absence of conventional sonoporation aids. U sing the optimised ultrasound conditions to facilitate cell membrane poration, I further adapted the ultrasound exposure configuration to demonstrate high-level gene transfer and expression in vitro. In doing so I was able to elucidate an optimised ultrasound-based transfection protocol and I further demonstrated that, with judicious choice of genetic material, it was possible to achieve very significant long term expression of a transgene in normal tissues and in tumours in vivo. The potential of the outcomes of my research is discussed in the context of medical therapeutics.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available