This thesis focuses on designing and synthesis of novel molecular imaging probes based on non-covalent funtionalisation of pure single-walled carbon nanotubes (SWNTs). Several synthetic strategies for the supramolecular chemistry functionalisation of SWNTs, cytotoxicity measurements and cellular imaging of supramolecularly functionalised carbon nanotube probes are discussed. Chapter one is a literature review as the thesis Introduction. This describes aspects of the physical and chemical properties, structural importance and synthesis methods of single-walled carbon nanotubes (SWNTs), also opens the discussion of the different functionalisation methods to enhance the solubility and biocompatibility of SWNTs for biomedical applications. Several approaches for the design of functionalisation SWNTs for molecular imaging reported in the current literature are highlighted. Techniques and facilities for accessing cell imaging ability and behavior of these synthesized molecular imaging probes, including confocal laser scanning microscopy (CLSM) and fluorescence-lifetime imaging microscopy (FLIM) are described briefly. Chapter two explores the synthesis of specifically designed naphthalene diimide (NDI). These molecules are known to form 3 dimensional (3D) helical organic nanotubes through hydrogen bonding. In this work an iodine-tagged NDI was allowed to self-assemble onto the surface of SWNTs. The cavities of the NDI organic nanotubes can accommodate SWNTs strands in their hydrophobic interior as observed high-resolution transmission electron microscopy (HR TEM). A new hybrid material, NDI@SWNT, was prepared and characterised as dispersed in organic solvents and aqueous media and in the solid state by HR TEM, tapping mode atomic force microscopy (TM AFM), scanning electron microscopy (SEM), circular dichroism, Raman and fluorescence spectroscopies (steady-state single and two-photon techniques). These measurements indicate that amino acid-functionalised NDI interacts strongly with SWNTs in dispersions and forms a donor-acceptor complex denoted NDI@SWNT. The interaction of this nanohybrid with cancer cells was explored using fluorescence microscopies. Chapter three describes the synthesis of series of molecular imaging agents based on two cancer targeting peptides (bombesin and RGDfK). Two types of NDIpeptide conjugates (Iodine-tagged NDI-Bombesin and Tryptophan-NDI-RGDfK) were designed and synthesized through EDC-coupling method. New compounds synthesized were characterised by mass spectroscopy and also HPLC. Fluorescence lifetime imaging microcopy and confocal laser scanning microscopy were utilised for investigating cellular behaviors (stability, fluorescence intensity and localization) of these molecular imaging probes. Chapter four describes the synthesis of amphiphilic conjugated thiophenes (dodecathiophene, denoted as T12). In this system, the thiophene backbone structure was chosen as a biocompatible coating for carbon nanotubes as simple molecular mechanics modeling suggested that it would be perfectly fitted to the curvature of SWNTs. T12 showed very good capability for debundling of SWNTs and forming corresponding solution dispersions of T12@SWNTs describes the potential of T12@SWNTs as a stable fluorescent bioimaging nano-probe for tracking cancer cells. Chapter five describes the successful filling of SWNTs with Cu2+ by radiochemistry methods (using 'hot' 64Cu ions anchored onto NaOAc) and also by a 'cold' optimised procedure for excess Cu(OAc)2. Filling with other metal ions was also tested, for example KReO4 and Zr(OAc)4. The filling experiments with Zr(OAc)4 in solution did not prove successful at normal pH but results were promising when pH was adjusted to ca. 2 by adding H2SO4. Any significant leakage of metal ions from open SWNTs was avoided by a simultaneous encapsulation of C70 molecules at the ends of SWNTs. Functionalisation of SWNTs by the supramolecular wrapping the surface of SWNTs in aqueous media with a naturally occurring glucan (β-1,3-1,4-Dglucan, denoted here as β-D-glucan) was also explored. Several boronic acid fluorophores were successfully synthesized and tested for the labeling of β-D-glucan @SWNTs by molecular recognition between boronic acids and this polysaccharide. Their cellular translocation behaviour and fluorescence properties were investigated by confocal fluorescence imaging and fluorescence lifetime imaging. Both methods show that localisation in sub-cellular (MCF-7 cells) regions and that the glucan coating significantly enhances the cell membrane translocation of SWNTs. Chapter six reports an efficient and economical strategy of supramolecular complex formulation of thermally reduced graphene. Naphthalene diimide (NDI) was used to form a stable and energy transfer complex which showed efficient quenching and significant red-shift of fluorescence of NDI when adsorbed onto graphene surfaces. The effect of thermally reducing annealing procedure to convert graphene oxides in graphene-nanoflake like materials was investigated. A new hybrid material (denoted here as NDI@TRG) synthesized was characterised by transmission electron microscopy (TEM), Raman spectroscopy, thermogravimetric analysis (TGA) and fluorescence microscopy in the dispersed phase Chapter seven contains full experimental details for the work described in this thesis. The Appendix contains details of the crystallographic data and supplementary information on cell imaging photos and fluorescence lifetime point decay data for SWNT nanocomposites.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:669017 |
| Date | January 2013 |
| Creators | Hu, Zhiyuan |
| Contributors | Pascu, Sofia |
| Publisher | University of Bath |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
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