Use this URL to cite or link to this record in EThOS: https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.735596
Title: Measuring redox potential in 3D breast cancer tumour models using SERS nanosensors
Author: Jamieson, Lauren Elizabeth
ISNI:       0000 0004 6499 8754
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 2016
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Abstract:
Cellular redox potential is incredibly important for the control and regulation of a vast number of processes occurring in cells. Disruption of the fine redox balance within cells is has been associated with disease. Of particular interest to my research is the redox gradient that develops in cancer tumours, in which the internal regions are further from vascular blood supply and therefore become starved of oxygen and hypoxic. This makes treatment of these areas a lot more challenging, as radiotherapy approaches rely on the presence of oxygen and, with a poor vascular blood supply, drugs delivered through the blood stream will have poor access to these regions. Currently, there is limited knowledge regarding the quantitative nature of this redox gradient in cancerous tumours. To aid the development of drugs and therapies to overcome this problem, a system that enables quantitative mapping of redox potential through a tumour would be a vital tool. In this work redox sensitive molecules attached to gold nanoparticles (NPs) are delivered to cells and give signals using surface enhanced Raman scattering (SERS). Redox potential changes are monitored quantitatively by ratiometric changes in signal intensity of selected signals in the SER spectra acquired. Multicellular tumour spheroids (MTS) are used as a three dimensional (3D) in vitro tumour model, in which the 3D architecture and gradients observed in tumours in vivo develop. As redox potential is pH dependent and pH is another important physiological characteristic in its own right, a SERS pH sensor was developed and ultimately a system that multiplexes intracellular pH and redox measurement by SERS. Initially, simultaneous redox potential and pH measurements were performed in monolayer culture before extending this to MTS. Photothermal optical coherence tomography (OCT) was used to investigate overall 3D NP distribution in the MTS models. It was possible to control NP delivery to MTS to localise NPs to various regions. Redox potential and pH could then be measured using a fibre optic Raman probe, and spatial response to drug treatment monitored. Intracellular NP localisation was investigated using transmission electron microscopy (TEM), scanning electron microscopy (SEM), helium ion microscopy (HIM) and confocal fluorescence microscopy (CFM) and attempts were made to control NP delivery to particular intracellular compartments.
Supervisor: Campbell, Colin ; Langridge-Smith, Patrick Sponsor: Engineering and Physical Sciences Research Council (EPSRC)
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.735596  DOI: Not available
Keywords: Raman scattering (SERS) ; cancer ; redox ; multicellular tumour spheroids
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