AbstractMedicine typically takes a one size fits all approach, a single treatment protocol is given to all patients with a disease. Whilst this is appropriate when all individuals express a similar, homogenous phenotype, not all diseases are genetically equal. Cancer is an example of a highly heterogenous disease. The intrinsic microenvironmental differences between healthy and cancerous cells can be exploited in the design of diagnostic and theranostic agents. Early detection tools are necessary in the case of cancers to better patient prognosis. There has been significant advancement in the field of fluorescent sensors to detect disease states, such that fluorescence spectroscopy has proven itself as an essential tool for study of targets in biological systems.
In this work, we have sought to develop a series of reaction based dual-activated fluorescent probes and theranostic molecules. In dual-activation; there is conditional release of a target fluorophore in the presence of two, independent activating analytes. If a single analyte is present, there is no fluorescence response. Dual activated sensors have an advantage over single analyte sensors as there is limited expression of novel analytes in cancer cells, only different concentrations of existing analytes. In the design of theranostics, we have combined therapy and diagnostics into a single molecule through labile chemical bonds. Chapters one and two describe the development of ‘dual activated’ probes based on resorufin and fluorescein motifs. In chapters three and four, the development of coumarin and benzimidazole based theranostics are discussed.
|Date of Award
|1 Apr 2020
|Tony James (Supervisor), Frank Marken (Supervisor) & Steven Bull (Supervisor)