AbstractThis work describes investigations into novel fluorescent nanohybrids based on carbon nanomaterials for the optical imaging of prostate cancer cells. The synthesis and characterisation of the different components of the nanoprobes are described within each chapter. The cellular response of as-prepared fluorophores, peptide conjugate and nanoprobes was evaluated in PC-3 cells by optical microscopy techniques for the first time. The new fluorescent conjugate synthesised showed targeted behaviour towards prostate cancer cells and the functional hybrids showed promising characteristics as synthetic scaffolds for future imaging nanomaterials.Chapter 1 describes the context of this work, including different imaging modalities applied to the diagnosis, staging and follow-up of prostate cancer. The use of bombesin as a targeting peptide for prostate cancer, and its incorporation in different imaging probes from current state-of the-art is discussed. The use of specific imaging probes as thiosemicarbazonato-based species is described, due to their current importance in tumour hypoxia detection and multimodality imaging potential. Finally, the use of single walled carbon nanotubes as biomedical scaffolds with a special interest in imaging applications is reviewed.Chapter 2 describes synthetic approaches towards novel functional unsymmetrical thiosemicarbazonato metal complexes. The synthesis of functional novel thiosemicarbazides and the formation of the thiosemicarbazone ligands is reported hereby. Several aromatic dicarbonylic starting materials (other than the known acenaphthenequinone) were explored and a panel of new zinc thiosemicarbazonato complexes were obtained and characterised spectroscopically.Chapter 3 contains the synthesis of bifunctional BODIPY derivatives which incorporate a protected amino acid residue. The synthetic approach towards new derivatives with fluorescence emission in the near-infrared region of the spectra is also reported.Chapter 4 describes the methodology towards the incorporation of the new carbon nanomaterial scaffold. The functionalisation of pristine single walled carbon nanotubes and graphene oxide to incorporate linkers in the structure, and the characterisation of the functionalised materials, are given hereby.Chapter 5 contains the synthesis and purification of the targeting peptide and the BODIPY-peptide conjugate involved as key components for the novel nanohybrids. Other nanohybrids containing the BODIPY or gallium thiosemicarbazonato species are also reported. The behaviour of these compounds in living PC-3 cells was evaluated and the cytotoxicity of a selection of compounds determined, for the first time.Chapter 6 provides a summary of the work carried out during this thesis and some proposals for future work arising from the research findings described herein.Chapter 7 contains detailed experimental details and characterisation data for the compounds described.The Appendices provide supporting spectroscopic evidence and X-ray diffraction data for the new compounds synthesised.
|Date of Award||1 Mar 2017|
|Supervisor||Sofia Pascu (Supervisor), Pedro Estrela (Supervisor), Rex Tyrrell (Supervisor) & Christopher Frost (Supervisor)|
Investigations into New Functionalised Thiosemicarbazones and Related Carbon Nanohybrids for the Imaging of Prostate Cancer
Cortezon Tamarit, F. (Author). 1 Mar 2017
Student thesis: Doctoral Thesis › PhD