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Title: Investigations into the supramolecular chemistry of graphene biocomposites : towards prostate cancer theranostics design, imaging and biosensing
Author: Tyson, James Abner
ISNI:       0000 0004 6352 6851
Awarding Body: University of Bath
Current Institution: University of Bath
Date of Award: 2016
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Chapter 1 includes the Introduction and literature review which describes current developments within the field of in vitro/vivo imaging of cancers, with a particular emphasis on the techniques employing fluorescence emission-based spectroscopy and imaging modalities. Examples are cited whereby graphene and its congeners have been used in conjunction with various fluorophores and peptide sequences as a means of achieving highly specific imaging probes. This section discusses aspects of energy transfer and the possibility that molecular probes can be designed to achieve both therapeutic goals and diagnosis (Theranostics). This review concludes with a discussion of the use of organic supramolecularly assembled imaging agents as a means of achieving thermodynamically controlled nano-constructs for the functionalisation of graphenes and their potential future applications as theranostic agents. Chapters 2, 3 and 4 describe the synthesis of chiral and naphthalene diimides (NDIs) which are fluorescent. Spectroscopic investigations in the solution phase are described and the propensity for aggregation in these systems is discussed. The specific nature of the self-assembly processes involved is explored in different solvent systems and in the solid state. Fluorescence lifetime imaging microscopy (FLIM) and laser scanning confocal microscopy (LSCM) are used to investigate the cellular uptake of the NDI molecules and their capacity to image living prostate cancer cells (PC-3). The NDIs are subsequently complexed supramolecularly to poly-aromatic carbon systems such as C60 and coronene (Chapter 3), as well as thermally reduced graphene oxide (Chapter 4). Chapter 3 describes the explorations into the modelling of the donor-acceptor interactions between the NDIs and the C60/coronene in order to establish binding stoichiometry and association constants. Both Chapters 3 and 4 discuss fluorescence titration and time correlated single photon counting (TCSPC) experiments which were performed as a means of establishing the presence of excited state energy transfer mechanisms. The chapters conclude with investigations in living cells in order to establish retention of in vitro fluorescence, with particular attention being paid to confirming the graphene complex stability. Chapter 5 describes the synthesis and functionalisation of a seven amino acid sequence peptide known as the G-receptor protein (GRP) binding unit of the polypeptide bombesin. The sequence binds GRPs that are known to be up-regulated in prostate cancer carcinoma and it has been widely utilised in the literature as a means of enhancing the up-take of various cancer imaging agents that employ a variety of imaging modalities. The peptide was attached to the fluorescent NDIs via carbodiimide activation protocols with the purpose of providing added specificity to the imaging agent with respect to PC-3 cells. Prior to NDI derivatisation with bombesin, electrochemical impedance spectroscopy (EIS) has been performed to establish the extent to which the peptide sequence binds to prostate cancer cells over healthy ones. The chapter concludes with confocal microscopy of the bombesin derivative NDI complexed to thermally reduced graphene oxide as a means of validating the utility of the fluorescent targeted bioconjugate as synthetic scaffolds for future early diagnosis and sensing devices for prostate cancer. Chapter 6 constitutes the summary of this work and highlights several possible areas of future developments of relevance to the results discussed and related future experiments proposed to fully validate the device assembly for prostate cancer sensing. Chapter 7 contains the Experimental section and the relevant data gathered over the course of the investigations. Additional supporting figures or data referred to but not included in the main text of the thesis are reported in the Appendices.
Supervisor: Pascu, Sofia ; Estrela, Pedro ; Marken, Frank ; Tyrrell, Rex Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: Graphene ; Prostate cancer ; Bioimaging probes ; Fluorescence ; Naphthalenediimides ; Supramolecular chemistry