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    Towards The Generation of Functionalized Magnetic Nanowires to Target Leukemic Cells

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    Nouf Alsharif Thesis 2016.pdf
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    Nouf Alsharif Thesis
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    Type
    Thesis
    Authors
    Alsharif, Nouf cc
    Advisors
    Kosel, Jürgen cc
    Committee Members
    Ravasi, Timothy cc
    Merzaban, Jasmeen cc
    Program
    Bioscience
    KAUST Department
    Biological and Environmental Sciences and Engineering (BESE) Division
    Bioscience
    Date
    2016-04
    Permanent link to this record
    http://hdl.handle.net/10754/607655
    
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    Abstract
    In recent years, magnetic nanowires (NWs) have been widely used for their therapeutic potential in biomedical applications. The use of iron (Fe) NWs combines two important properties, biocompatibility and remote manipulation by magnetic fields. In addition the NWs can be coated and functionalized to target cells of interest and, upon exposure to an alternating magnetic field, have been shown to induce cell death on several types of adherent cells, including several cancer cell types. For suspension cells, however, using these NWs has been much less effective primarily due to the free-floating nature of the cells minimizing the interaction between them and the NWs. Leukemic cells express higher levels of the cell surface marker CD44 (Braumüller, Gansauge, Ramadani, & Gansauge, 2000), compared to normal blood cells. The goal of this study was to functionalize Fe NWs with a specific monoclonal antibody towards CD44 in order to target leukemic cells (HL-60 cells). This approach is expected to increase the probability of a specific binding to occur between HL-60 cells and Fe NWs. Fe NWs were fabricated with an average diameter of 30-40 nm and a length around 3-4 μm. Then, they were coated with both 3-Aminopropyl-triethoxysilane and bovine serum albumin (BSA) in order to conjugate them with an anti-CD44 antibody (i.e. anti-CD44-iron NWs). The antibody interacts with the amine group in the BSA via the 1-Ethyl-3-3-dimethylaminopropyl-carbodiimide and N-Hydroxysuccinimide coupling. The NWs functionalization was confirmed using a number of approaches including: infrared spectroscopy, Nanodrop to measure the concentration of CD44 antibody, as well as fluorescent-labeled secondary antibody staining to detect the primary CD44 antibody. To confirm that the anti-CD44-iron NWs and bare Fe NWs, in the absence of a magnetic field, were not toxic to HL-60 cells, cytotoxicity assays using XTT (2,3-Bis-2-Methoxy-4-Nitro-5-Sulfophenyl-2H-Tetrazolium-5-Carboxanilide) were performed and resulted in a high level of biocompatibility. In addition, the internalization of the coated NWs have been studied by coating them with a pH dependent dye (pHrodoTM Red) that showed a signal once the NWs were internalized by the cell.
    DOI
    10.25781/KAUST-49P8B
    ae974a485f413a2113503eed53cd6c53
    10.25781/KAUST-49P8B
    Scopus Count
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    Biological and Environmental Sciences and Engineering (BESE) Division; Theses

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