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Development of nanotechnology-based drug delivery and imaging system to the white adipose tissue vasculature using Wistar Rat ModelThovhogi, Ntevheleni January 2013 (has links)
Philosophiae Doctor - PhD / Obesity is a complex metabolic disease of excessive fat accumulation. It is a worldwide epidemic affecting billions of people and its pharmacological management is hampered by drug toxicity and undesirable side effects. Therefore, a need still exists for the development of safe medication for treatment of obesity. Nanotechnology involves the use of small particles at atomic and molecular scale. It has application in medical diagnostics, drug delivery and molecular imaging. Various nanoparticles (NPs) functionalized with different biomolecules have been successfully used in many therapeutic and research applications due to their versatility, ease of chemical synthesis, low toxicity and unique properties. Examples of NPs used in this study are Gold nanoparticles (GNPs) and Quantum dots (QDs). GNPs and QDs are extensively used as drug delivery, labelling and imaging tools in biomedical research. Nanotechnology offers a new potential useful avenue for solving the problem of toxicity of anti-obesity drugs. This could be achieved through targeted drug delivery. In this study, rats were fed a high fed diet (HFD) to induce obesity. The streptavidin conjugated GNPs and QDs were functionalized with biotinylated adipose-homingpeptide (AHP) and/or anti-obesity drug (Gallic acid). Functionalization was characterized using agarose gel electrophoresis, UV-vis spectroscopy and transmission electron microscopy. The binding-specificity and targeting ability of AHP was evaluated in vitro and in vivo. The apoptotic effect of AHP functionalized-drug loaded GNPs (AHP-GA-GNPs) was tested in vitro using APOPercentage TM and Caspase-3 activation assays. The in vitro data indicated that the binding was specific to prohibitin (PHB) expressing cells (MCF-7 and Caco-2), and that the binding was temperature dependent. PHB was confirmed as a target for AHP after overlaying AHP-FITC and anti-prohibitin antibody staining. Cellular uptake was detected on the cells treated with AHP-functionalized NPs as compared to unfunctionalized NPs. The GA and AHP-GA-GNPs reduced cellular viability and induced apoptosis through activation of Caspase-3. The Ex-vivo studies using primary endothelial cells (ECs) isolated from the WAT of lean and obese Wistar rats showed that the binding of AHP was receptor mediated, and specific to receptors differentially expressed in ECs from obese WAT. The in vivo studies showed that, treatment of obese rats with AHP-functionalized NPs resulted in targeted delivery of the NPs to the WAT as compared to those treated with unfunctionalized NPs. Qualitative analysis using fluorescence microscopy and IVIS Luminar XR, live-imaging system showed that the unfunctionalized NPs accumulated mostly in the organs of the reticuloendothelial system, namely: liver, spleen, lungs and kidneys. In contrast, AHP-functionalized NPs accumulated mostly in the WATs as compared to the rest of the organs of the obese rats. Uptake and binding of the NPs to the tissues was quantitatively confirmed by the inductive coupled plasma-optical emission spectroscopy (ICP-OES). In conclusion, this study reports the 1) successful functionalization of GNPs and QDs with AHP, 2) use of AHP-functionalized GNPs and QDs as delivery and imaging agents to the WAT, and 3) potential use of AHP-functionalized drug-loaded GNPs in the treatment of obesity.
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Electrochemical properties of self-assembled films of single-walled carbon nanotubes, monolayer-protected clusters of gold nanoparticles and iron (II) phthalocyanines at gold electrodesPillay, Jeseelan 04 June 2010 (has links)
This dissertation investigates the heterogeneous electron transfer dynamics and electrocatalytic behaviour of the following molecules immobilized on gold electrode: (a) 2-dimethylaminoethanethiol (DMAET), with and without integration with poly (m-aminobenzenesulfonic acid) functionalised single-walled carbon nanotubes (SWCNT-PABS); (b) SWCNT-PABS and iron (II) phthalocyanine nanoparticles (nanoFePc); (c) Colloidal gold / Gold nanoparticles (AuNP) and nanoFePc (d) ; water-soluble iron (II) tetrasulfophtalocyanine (FeTSPc) and SWCNT-PABS, and (e) novel monolayer protected gold nanoparticles (MPCAuNPs) by means of either (i) layer-by-layer (LBL) self-assembly or (ii) self-assembled monolayer (SAM) fabrication strategy. Atomic force microscopy and electrochemical studies (cyclic voltammetry, and electrochemical impedance spectroscopic) were used to monitor the substrate build-up, via strong electrostatic interaction. The surface pKa of DMAET was estimated at 7.6, smaller than its solution pKa of 10.8. It is also shown that SWCNT-PABS is irreversibly attached to the DMAET SAM. For layered films involving SWCNT-PABS and nanoFePc (Au-DMAET- SWCNT-PABS-nanoFePc) n (n=1-5 layers) as the number of bilayers increase, the electron transfer kinetics of the [Fe(CN) 6]3-/4 redox probe decreases. On the contrary, LBL assembly involving AuNP and nanoFePc (Au-DMAET-AuNP-nanoFePc) n (n=1-4 layers) shows an increase followed by a decrease in electron transfer kinetics subsequent to the adsorption of nanoFePc and AuNP layers, respectively. For SAMs involving FeTSPc and SWCNT-PABS, the mixed hybrid (Au-DMAET-SWCNT-PABS/FeTSPc) exhibited fastest charge transport compared to other electrodes. For the novel MPCAuNPs, the protecting or stabilizing ligands investigated were the (1-sulfanylundec-11-yl) tetraethylene glycol (PEG-OH) and the (1-sulfanylundec-11-yl) polyethylene glycolic acid (PEG-COOH). Three different mass percent ratios (PEG-COOH : PEG-OH), viz. 1:99 (MPCAuNP-COOH1%), 50:50 (MPCAuNP-COOH50%) and 99:1 (MPCAuNP-COOH99%) were used to protect the gold nanoparticles. The impact of these different ratios on the electron transfer dynamics in organic and aqueous media was explored. The average electron transfer rate constants (ket / s-1) in organic medium decreased as the concentration of the surface-exposed –COOH group in the protecting monolayer ligand increased: MPCAuNP-COOH1% (~ 10 s-1) > MPCAuNP-COOH50% (~ 9 s-1) > MPCAuNP-COOH99% (~ 1 s-1). In aqueous medium, the trend is reversed. This behaviour has been interpreted in terms of the hydrophobicity (quasi-solid nature) and hydrophilicity (quasi-liquid nature) of the terminal –OH and –COOH head groups, respectively. The ionization constants of the terminal groups (i.e., surface pKa) was estimated as ~ 8.2 for the MPCAuNP-COOH1%, while both MPCAuNP-COOH50% and MPCAuNP-COOH99% showed two pKa values of about 5.0 and ~ 8.0, further confirming the hydrophilicity / hydrophobicity of these surface functional groups. Hydrogen peroxide (H2O2), epinephrine (EP) and ascorbic acid (AA) were used as model analytes to examine electrocatalytic ability of these nanostructured assemblies. The electrochemical reduction of H2O2 at a constant concentration was amplified upon increasing bilayer formation of SWCNT-PABS and nanoFePc, while SWCNT-PABS/FeTSPc showed the best response towards the detection of epinephrine. MPCAuNP-COOH99% showed an excellent suppression of the voltammetric response of the AA and an enhanced electrocatalytic activity towards the detection of EP compared to the other MPCAuNPs. / Thesis (PhD)--University of Pretoria, 2010. / Chemistry / unrestricted
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Nanoestruturas de Dissulfeto de Molibdênio : síntese e caracterização para produção de hidrogênio / Molybdenum disulfide nanostructures: synthesis and characterization for hydrogen productionFraga, André Luis Silveira January 2017 (has links)
IV Resumo Título: Nanoestruturas de Dissulfeto de Molibdênio: Síntese e caracterização para produção de Hidrogênio Mestrando: André Luís Silveira Fraga Orientador: Prof. Marcos José Leite Santos Palavras Chave: nanoestruturas de MoS2, nanopartículas de ouro, semicondutores, produção de hidrogênio. Neste trabalho é apresentada a síntese e caracterização de nanoestruturas de MoS2 e nanoestruturas de MoS2 decoradas com nanopartículas de ouro. O MoS2 foi obtido através de rota hidrotermal a 200 °C durante períodos de síntese de 2, 6, 12 e 24 horas. Como precursores foram utilizados molibdato de sódio, ácido 3-mercaptopropiônico, cisteamina e L-cisteína. Para avaliar o efeito da presença dos ligantes nas estruturas, as amostras de MoS2 foram tratadas térmicamente a temperaturas de 250, 550 e 750 °C, em atmosfera de argônio. Com o objetivo de avaliar o efeito da presença de nanopartículas de ouro nas propriedades fotocatalíticas do material, foi realizada a síntese in situ de nanopartículas de ouro aderidas às estruturas de MoS2. Os materiais foram caracterizados através das técnicas de difração de raios X (DRX), microscopia eletrônica de transmissão (MET), microscopia eletrônica de varredura (MEV) e espectroscopia do ultravioleta e visível (UV-Vis). As áreas superficiais e quantidade de poros foram avaliadas através das técnicas de BET (Brunauer, Emmett and Teller) e DFT (density functional theory). O precursor ácido 3-mercaptopropiônico resultou na formação de aglomerados de nanofolhas com cerca de 500 nm de diâmetro na sua maior dimensão. Ao usar cisteamina e L-cisteína foram obtidas nanoestruturas com formato de nanoflores com cerca de 300 nm de diâmetro formadas por pétalas com cerca de 30 nm. Um resultado interessante foi a rápida formação das nanoflores na presença de L-cisteína. As estruturas de nanoflores apresentaram produção de hidrogênio de até 9,6 mmol/gh. / In this work the synthesis and characterization of MoS2 nanostructures and MoS2 nanostructures decorated with gold nanoparticles is presented. The materials were obtained by hydrothermal route at 200 °C during synthesis periods of 2, 6, 12 and 24 hours. Sodium molybdate was used as Molybdenium precursor and 3-mercaptopropionic acid, cysteamine and L-cysteine as sulfur precursors. To evaluate the effect of ligands on the structures, the MoS2 samples were thermally treated at 250, 550 and 750 °C under argon atmosphere. The effect of gold nanoparticles on the photocatalytic properties of the material was evaluated by obtaining and materials with gold nanoparticle adhered to the MoS2 structures. The materials were characterized by X-ray diffraction (XRD) techniques, transmission electron microscopy (TEM), scanning electron microscopy (SEM) and ultraviolet and visible spectroscopy (UV-Vis). The surface areas and amount of pores were evaluated using BET (Brunauer, Emmett and Teller) and DFT (density functional theory) techniques. The precursor 3-mercaptopropionic acid resulted in the formation of nano-foil agglomerates of about 500 nm in diameter. On the other hand, when using cysteamine and L-cysteine, flower-shaped nanostructures of about 300 nm in diameter formed by petals of about 30 nm were obtained. An interesting result was the rapid formation of nanoflores in the presence of L-cysteine. Nanoflower structures showed hydrogen production up to 9.6 mmol / gh.
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Modification of Chemical Vapor-Deposited Carbon Electrodes with Electrocatalytic Metal Nanoparticles through a Soft Nitriding TechniqueAmoah, Enoch 01 August 2019 (has links)
Metal nanoparticles have been widely used for many catalytic and electrocatalytic applications due to their larger surface area-to-volume ratios and higher densities of active sites compared to bulk materials. This has resulted in much interest in understanding the electrocatalytic behavior of metal nanoparticles with respect to their structure. However, most research on this topic has employed collections of nanoparticles. Due to difficulties in controlling and characterizing particle loading and interparticle distance in nanoparticle ensembles, single nanoparticles studies have recently become a topic of great interest. In this study, a soft nitriding technique was applied to chemical vapor-deposited carbon ultramicroelectrodes (UMEs) in order to immobilize ligand-free AuNPs onto the carbon substrate. The feasibility of this method is geared toward studying the properties of single AuNPs immobilized onto carbon nanoelectrodes. The ligand-free AuNPs immobilized onto the nitrided carbon UMEs were highly electrocatalytic toward methanol oxidation.
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Effects of gold nanoparticles on vascular endothelial growth factor-A-induced melanoma cell growth and angiogenesisMatutule, Lebogang Johanna 11 1900 (has links)
Melanoma is a skin cancer that relies on angiogenesis for growth and progression. Angiogenesis is the growth of new vessels from existing vessels and follows a number of steps that include endothelial cell growth, migration and tubulogenesis. Current anti-angiogenic drugs are not effective in the treatment of melanomas due to serious side effects such as hypertension and the development of resistance. On the other hand, gold nanoparticles (AuNPs) have been reported to be biocompatible in preclinical models. Furthermore, AuNPs were shown to be cytotoxic to prostate cancer cells. In human umbilical vein endothelial cells, AuNPs inhibited the angiogenic protein, vascular endothelial growth factor-A (VEGF-A). Therefore, the study aimed to investigate the possible cytotoxic effects of AuNPs (1.2–3.2 nM) on melanoma cells and angiogenesis parameters (endothelial cell growth and migration) as well as on the levels of angiogenesis promoting proteins, VEGF-A and placental growth factor (PIGF). Melanoma (B16-F10) cells and tumour-derived endothelial (sEnd.2) cells were maintained in an incubator in a humidified atmosphere containing 5% CO2 at a temperature of 37°C. To investigate whether AuNPs were cytotoxic to melanoma cells, the effect of the particles on B16-F10 cell survival was measured using the crystal violet assay. To determine the effects of AuNPs on angiogenesis parameters, endothelial cell (EC) growth and migration were investigated using crystal violet assay and the scratch assay respectively. Also, EC morphology was studied using polarisation-optical interference contrast light microscopy. The enzyme-linked immunosorbent assay (ELISA) was used to determine the effects of AuNPs on the levels of VEGF-A and PIGF. The results showed that AuNPs decreased the viability of melanoma and endothelial cells. The scratch assay showed that more ECs migrated in cultured treated with AuNPs (P < 0.05). The concentration of VEGF-A and PIGF was reduced significantly following treatment with AuNPs, meaning that the particles exhibited anti-angiogenic properties. This outcome provides a basis for further testing of AuNPs as a potential treatment for melanoma. / Dissertation (MSc)--University of Pretoria, 2020. / National Research Foundation / Mintek / Physiology / MSc / Unrestricted
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Synthesis and Characterization of ACE2-Based Peptides as Inhibitors & Peptide Epitopes for the Detection of SARS-CoV-2Alsawaf, Sarah 11 1900 (has links)
Due to the pandemic, research concerning SARS-CoV-2 became of the utmost importance. In this research, we aimed to find and synthesize a library of peptide epitopes that carry functional properties of the ACE-2 receptor binding to the virus protein for the purpose of creating a therapeutic treatment (i.e. viral inhibition). In order to do this, we used MST to determine binding affinity. After that, we validated the binding properties of our peptide epitopes and applied them as SARSCoV-2 antibody indicators using ELISA. We, then, functionalized gold nanoparticles with the peptide epitopes to assess its utility as a potential SARS-CoV-2 competitive inhibitor. From the set of peptides in the library, P25 showed the most functional properties in both MST and serological ELISA, while P1 successfully conjugated to the gold nanoparticles in different forms (PEG-P1, linker-P1, and mutated P1). Finally, P1 was validated to have antibody binding through sandwich ELISA. In the future, these findings can be applied to inhibit viral activity through drug delivery.
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Nanoformulation of Artemisia afra and its potential biomedical applications in type 2 diabetesLiebenberg, Nicole Albertha-Wade January 2019 (has links)
>Magister Scientiae - MSc / Current research classifies Type 2 diabetes as most prevalent non-communicable diseases in South
Africa. Approximately 285 million people are affected globally with an expected increase to 595
million by the year 2035. Synthetic first-line drugs in the treatment of Type 2 diabetes, have been
shown to have an efficacy rate of approximately 43% as a result of poor drug uptake and
metabolism. Furthermore, given South Africa’s uniquely diverse botanical heritage, herbs
commonly used traditional medicine have shown promise in the treatment of Type 2 diabetes.
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Towards monodisperse Silicon Nanocrystals: density gradient centrifugation applied on commercial gold nanoparticlesKhavari, Faraz January 2016 (has links)
The application of silicon nanocrystals as non-toxic bio-labels and downconverters requires their uniform size distribution in order to minimize the inhomogeneous broadening of the photoluminescence peak. In this thesis, we set the basis for their size-separation via the density-gradient centrifugation method. To be more precise, we successfully apply this technique to separate 5 and 10 nm gold nanoparticles from an ensemble by using an engineered medium layer stack. In addition, we explain how atomic force microscopy is used to measure the size of the nanoparticles, with a particular attentionon the removal of unwanted solvent-related effects. As a future plan, we will implement the technique for the size-separation of silicon nanocrystals.
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Optical and microarray silver-gold based sensors for the detection of e.coli 0157:h7 in seawaterNqunq, Sphamandla January 2021 (has links)
>Magister Scientiae - MSc / Recently researchers reported that nanoparticles functionalised through chemical methods possess risks to the environment and to the human health since they use hazardous chemicals and produce toxic waste. The increasing demand of nanomaterials for application in the field of science require an alternative method for synthesis of nanomaterials that are environmentally friendly, eco-friendly and non-toxic. The present study describes the green synthesis method for functionalisation of nanomaterials. Green synthesis methods are considered as a novel approach for functionalisation of nanoparticles using biological sources. / 2022
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Bright upconverted emission from light-induced inelastic tunnelingRakhmatov, Eradzh 27 January 2020 (has links)
Upconverted light from nanostructured metal surfaces can be produced by harmonic generation and multi-photon luminescence; however, these are weak processes and require extremely high field intensities to produce a measurable signal. Here we report on bright emission, five orders of magnitude greater than harmonic generation, that can be seen from metal tunnel junctions due to light-induced inelastic tunneling. Like inelastic tunneling light emission, which was recently reported to have 2% conversion efficiency per tunneling event, the emission wavelength recorded varies with the local electric field applied; however, here the field is from a 1560 nm femtosecond pulsed laser source. Finite-difference time-domain simulations of the experimental conditions show the local field is sufficient to generate tunneling-based inelastic light emission in the visible regime. This phenomenon is promising for producing ultrafast upconverted light emission with higher efficiency than conventional nonlinear processes. / Graduate
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