Browsing by Author "Swartz, Lauren Taryn"

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    Aptamer selection against GFRa1 for its application in the prognosis of breast cancer
    (University of the Western Cape, 2019) Swartz, Lauren Taryn; Meyer, Mervin
    Breast cancer is the second most common cancer amongst South African women. Despite ongoing efforts to combat breast cancer, current prognostic and/or therapeutic monitoring methods are limited since very little improvement, in the rate of long term recurrence of breast cancer, has been observed. Considering this, developing novel strategies to detect breast cancer recurrence – at an early onset – is crucial for monitoring the disease and potentially preventing disease progression. Methods currently used for the detection of BC are costly and can also be very uncomfortable for the patient. These methods are also too costly to use as a routine test, following surgery or treatment to assess disease progression. Thus, developing a cost-effective detection method appears to be an appealing alternative. Serum/blood-based biomarkers are ideal targets for the development of low cost detection assays. Two candidate biomarkers, unique ligand binding protein 2 (ULBP2) and glial cell line-derived neurotrophic factor family receptor alpha 1 (GFR1) were identified using bioinformatics and proteomics, respectively. These biomarkers have demonstrated to be useful prognostic biomarkers for breast cancer. The selection of aptamers against these biomarkers can facilitate the development of cost-effective detection methods. Aptamers are short DNA or RNA oligonucleotides that have very high affinity and specificity for its targets and can potentially replace antibodies as tools for molecular recognition in detection systems, such as the enzyme-linked immunosorbent assay (ELISA), lateral flow assays and electrochemical biosensors.
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    Discriminative eradication of cancer cells using quantum dots functionalised with peptide-directed delivery of a pro-apoptotic peptide
    (2013) Swartz, Lauren Taryn; Meyer, Mervin; Onani, Martin
    The 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.