Diphenylalanine (FF) peptide is the core-recognition motif of β-amyloid polypeptide, a peptide associated with diseases such as Alzheimer’s and which is known to be capable of self-assembly. FF has attracted interest in nanotechnology due to the physical and chemical stability and mechanical rigidity of the self-assembled nanotube form of the peptide. A number of promising applications of FF nanotubes have previously been explored. To extend this work to biomedical and pharmaceutical areas, an improved understanding of the physicochemical properties of FF tubes, together with the influence of assembly conditions, cytotoxicity properties and potential in drug delivery field are presented in this thesis. The studies presented in Chapter 2 address the self-assembly of FF peptide prepared by two known methods of preparation, one aqueous based, the other utilizing an organic solvent. A range of complementary characterization methods is applied including atomic force microscopy, scanning electron microscopy, focused ion beam-scanning electron microscopy, X-ray powder diffraction, and Raman Spectroscopy. The investigations reveal differences in morphology of the tubes formed by the different preparation methods. The aqueous based method produces tubes that are long, straight and unbranched and are consistent with previous work. The alternative organic solvent method produced tubes that are shorter and narrower. In addition, these tubes displayed flexibility and nucleation points. Following on from these findings, a proposed mechanism of tube growth is discussed. Chapter 3 further extends the investigation to the biological field. Possible cytotoxicity issues are studied using a MTT assay on a HeLa cell line. Moreover, total internal reflection microscopy was applied to investigate HeLa cell behaviour in the presence of FF nanotubes. The results from these studies reveal that the nanotubes and FF peptide do not cause any mitochondrial related damage to HeLa cells. Furthermore, short tubes were observed to be taken up by cells through a suggested macropinocytosis pathway. Finally, in Chapter 4 the focus turns to the investigation of the potential of FF tubes as drug carriers in drug delivery. Here, successful synthesis of drug-loaded FF tubes is presented with two model drugs. The physical characterization of the complex formed under different conditions using scanning electron microscopy reveals FF nanotube self-assembly is a drug concentration and solvent type dependent process. Finally, in vitro drug release from FF nanotubes is performed and compared to that of the drug alone. Extended drug release is observed for both drug candidates and release mechanisms are proposed. The results presented throughout this thesis demonstrate the versatility of self-assembling FF peptides for the formation of tubular nanostructures with different morphologies and physical properties under different conditions. The assembled nanostructures appear non-toxic to cells and offer promise in drug delivery as novel drug carriers.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:547901 |
| Date | January 2011 |
| Creators | Xu, Kairuo |
| Publisher | University of Nottingham |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://eprints.nottingham.ac.uk/12300/ |
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