Cardiovascular diseases are the leading cause of mortality worldwide, with the majority of these deaths being a result of the inflammatory pathology, atherosclerosis. A critical need for multi-parameter molecular imaging has been identified to facilitate improved atherosclerosis diagnosis and the understanding of local inflammatory pathways in humans. Established imaging modalities such as ultrasound and magnetic resonance imaging are being investigated as potential solutions to this clinical problem, however, inherent limitations with these technologies have resulted in the exploration of alternate imaging approaches. This thesis focuses on the development and testing of surface enhanced Raman spectroscopy (SERS), a promising and novel molecular imaging modality, for the molecular imaging of vascular inflammatory biomarkers in vitro, ex vivo and in vivo. SERS detects molecule specific vibrational signals which are enhanced when an analyte is excited with light in close proximity to a noble metal surface. To achieve molecular specificity and surface enhancement, we developed antibody functionalised gold nanoparticles (nanotags) designed to bind to our molecular targets of interest, the adhesion molecules, intercellular adhesion molecule (ICAM)-1, vascular cell adhesion molecule (VCAM)-1 and P-selectin, and produce a SERS signal detectable by spectroscopy and/or microscopy based approaches. In vitro, we demonstrate the simultaneous and quantifiable SERS detection of ICAM-1, VCAM-1 and P-selectin on TNFa stimulated human endothelial cells. We subsequently demonstrated the simultaneous SERS detection of ICAM-1, VCAM-1 and P-selectin in freshly isolated atherosclerotic human coronary artery ex vivo. Finally, we explored SERS imaging in a humanised mouse model, demonstrating non-invasive multiplex imaging of adhesion molecules in vivo. In summary, this proof of concept study demonstrates the suitability of SERS and nanotags for the non-invasive molecular imaging of vascular inflammation. We have tested this approach with increasing biological complexity and highlighted SERS as a potential molecular imaging tool for future clinical translation in the context of vascular inflammation, atherosclerosis and cardiovascular disease.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:739276 |
| Date | January 2018 |
| Creators | Noonan, Jonathan |
| Publisher | University of Glasgow |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://theses.gla.ac.uk/8939/ |
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