Browsing by Author "Gwanzura, Takunda"

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    Engineering carbon nanotubes as therapeutic nanocarriers of Tulbaghia violacea, Annona muricata, Dicoma capensis and Dodonaea viscosa plant-based extracts, targeting breast and colorectal cancer
    (Stellenbosch : Stellenbosch University, 2023-12) Gwanzura, Takunda; Perold, Willem; Stellenbosch University. Faculty of Engineering. Dept. of Electrical and Electronic Engineering.
    ENGLISH ABSTRACT: Cancer is one of the most prevalent diseases globally and it is characterized by uncontrolled rapid cell division and differentiation. Lack of tumour specificity, dose-related toxicity and low bioavailability of chemotherapy drugs are major hindrances to cancer treatment. Nanotechnology has given the platform to selectively interact with cancerous cells and increase cellular uptake and drug localization. Functionalisation of nanoparticles can be done to recognize cancer cells and giving accurate and selective drug delivery which does not interact with healthy cells. In order to develop more efficient therapeutic regimes, a better understanding of the type of nanoparticles suitable for drug delivery is required. Over the past years, carbon nanotubes have been used as nanocarriers to transport anticancer drugs, genes, and proteins for chemotherapy. Furthermore, the possibility of conjugating carbon nanotubes with anticancer plant-based drugs creates advanced therapeutic applications. Therefore, the aim of this project was to develop a single-walled carbon nanotube (SWCNT) nanocarrier bio-conjugated with plant-based bioactive compounds which can target can- cer cells specifically. The first phase of the study involved purification and functionalisation of carbon nanotubes. Hydrochloric acid was used to purify the carbon nanotubes and functionalisation was done with polyethylene glycol (PEG) and folic acid (FA). Fourier transform infrared (FTIR) spectroscopy was used to confirm functionalisation. Four plants were identified and used, namely Annona muricata, Dodonaea viscosa, Dicoma capensis and Tulbaghia violacea. Two plant extraction methods were assessed, and the closed loop extraction method obtained the most bioactive compounds from the plant extracts. The results were confirmed by liquid chromatography-mass spectrometry (LC-MS) analysis. This was followed by bio-conjugation of the functionalised carbon nanotubes with bioactive compounds from the four plants. Ultraviolet–visible (UV-Vis) spectroscopy was used to confirm bio-conjugation. In vitro cytotoxicity studies were undertaken to assess the effects of bioactive compounds and bio-conjugates in breast cancer cell lines (MCF-7 and MDA-MB-231), a colon cancer cell line (HT-29) and a non-tumorigenic breast epithelial cell line (MCF-12A). The in vitro cytotoxicity results showed a low cell viability for cancer cell lines whilst that for normal cells remained higher. The half-maximal inhibitory concentration (IC50) values were determined, and all plants showed a value lower than 30 μg/ml. The selectivity index (SI) of the plant extracts was also calculated and all plants showed a high SI value greater than 2. The bio-conjugates showed a higher cell viability in normal cells and a lower cell viability in cancer cells compared to plant extracts alone, which was due to the conjugation with carbon nanotubes improving selectivity and efficacy. Furthermore, the bio-conjugate with all four plant extracts mixed had the lowest cell viability in all cancer cell lines indicating synergism. The mechanisms of cellular uptake were determined by fluorescence microscopy and it was observed that folate receptor mediated endocytosis and caveolae mediated endocytosis both took place for bio-conjugate cellular internalization. The type of cell death occurring in cancer cells was determined by flow cytometry studies. It was confirmed that both apoptosis and necrosis took place in the cancer cells. In conclusion, the carbon nanotubes were successfully used as nanocarriers and their bio-conjugation with plant based bioactive compounds improved efficacy and selectivity towards cancer cells in this study.