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dc.contributor.advisorMeyer, Mervin
dc.contributor.advisorOnani, Martin
dc.contributor.authorSwartz, Lauren Taryn
dc.date.accessioned2014-11-17T10:20:40Z
dc.date.available2014-11-17T10:20:40Z
dc.date.issued2013
dc.identifier.urihttp://hdl.handle.net/11394/3862
dc.description>Magister Scientiae - MScen_US
dc.description.abstractThe therapeutic goal of cancer treatment is to trigger selective cell death in cancer cells. To eliminate cancerous cells effectively, the anti–cancer drugs must be targeted to the affected cells. However, anti–cancer drugs are often distributed non–specifically giving rise to systemic toxicities and other adverse effects. Cancer specific peptides are useful cancer targeting agents that can be used for the targeted delivery of anti-cancer drugs. Several cancer targeting peptides and some of their corresponding protein targets have been identified. Previous work investigated the specific binding of five of these peptides (p.C, p.H, p6.1, Frop-1 and p.L) conjugated to fluorescent nanoparticles (quantum dots) to a panel of human cell lines, which included four cancerous cell lines (Caco-2, HeLa, HT29 and HepG2) and one non-cancerous cell line (KMST-6). Flow cytometry showed that the p.L peptide preferentially bind to HT29 cells; suggesting that the expression levels of the target for the p.L peptide are higher in these cells. The objective of this study was to make use of target specific functionalised quantum dots (QDs) to deliver Second mitochondria-derived activator of caspases/ Direct AIP binding protein with low PI (Smac/DIABLO) to HT29 cells with the aim of enhancing the effects of pro-apoptotic drugs. Smac/DIABLO is a pro-apoptotic peptide that is able to interact with inhibitor of apoptosis proteins (IAPs), thereby inducing pro-apoptotic signalling. Methodology: CdSe/ZnS core-shell QDs were synthesised using the one-pot synthesis method. These QDs were characterised using photoluminescence (PL) spectroscopy, high resolution transmission electron microscopy (HR-TEM) and energy dispersive x-ray spectroscopy (EDS). The CdSe/ZnS core-shell QDs were solubilised with L-cysteine (Cys- QDs). The Cys-QDs were bi-conjugated to the p.L peptide and Smac peptide using 1-ethyl-3- (30-dimethylamino) carbodiimide (EDC) chemistry. Cultured HT29 cells were exposed to the 10 | P a g e QD peptide bi-conjugates and fluorescence microscopy was employed to assess targeting and internalisation. The cytotoxicity of the QD peptide bi-conjugates in combinatorial treatment with ceramide was evaluated using the WST-1 Cell Proliferation assay. A commercially available QD with similar chemistry was used to carry out a comparative study to relate the efficiency of the in-house synthesized QD.en_US
dc.language.isoenen_US
dc.subjectApoptosisen_US
dc.subjectBi-conjugationen_US
dc.subjectCancer specific peptidesen_US
dc.subjectEDCen_US
dc.subjectFluorescenceen_US
dc.subjectNanotechnologyen_US
dc.subjectQDsen_US
dc.subjectSmac/Diabloen_US
dc.subjectSelective killingen_US
dc.subjectTargeted deliveryen_US
dc.titleDiscriminative eradication of cancer cells using quantum dots functionalised with peptide-directed delivery of a pro-apoptotic peptideen_US
dc.rights.holderuwcen_US


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