• Login
    View Item 
    •   UMB Digital Archive
    • School, Graduate
    • Theses and Dissertations All Schools
    • View Item
    •   UMB Digital Archive
    • School, Graduate
    • Theses and Dissertations All Schools
    • View Item
    JavaScript is disabled for your browser. Some features of this site may not work without it.

    Browse

    All of UMB Digital ArchiveCommunitiesPublication DateAuthorsTitlesSubjectsThis CollectionPublication DateAuthorsTitlesSubjects

    My Account

    LoginRegister

    Statistics

    Display statistics

    Targeted delivery of nitroxide spin probes, using immunoliposomes, for electron paramagnetic resonance imaging of tumors in vivo

    • CSV
    • RefMan
    • EndNote
    • BibTex
    • RefWorks
    Thumbnail
    Name:
    Legenzov_umaryland_0373D_10897.pdf
    Size:
    3.609Mb
    Format:
    PDF
    Download
    Author
    Legenzov, Eric Anthony
    Advisor
    Kao, Joseph P. Y.
    Date
    2017
    Type
    dissertation
    
    Metadata
    Show full item record
    Abstract
    Metastasis is the cause of approximately 90% of cancer-associated deaths. Detection of metastatic lesions is a major clinical challenge and current imaging methods frequently fail to detect micrometastases (0.2 - 2.0 mm). Electron Paramagnetic Resonance Imaging (EPRI) is an emergent in vivo imaging modality. In an analogous manner to MRI, EPRI detects magnetic-field-induced resonant absorption of radio-frequency light. The key difference is that EPRI involves resonant absorption by the unpaired electrons in paramagnetic free radicals, whereas MRI involves resonant absorption by hydrogen nuclei (protons). Because the free radical concentration in the body is negligible, EPRI requires the use of exogenous stable free radicals - known as spin probes. The use of exogenous spin probes in EPRI is a key advantage that allows high signal-to-background contrast generation. Therefore, EPRI represents an ideal in vivo imaging technique for identifying and locating metastatic lesions in cancer. Liposomes are lipid bilayer vesicles that can encapsulate a wide variety of molecules in their aqueous lumen. Antibody conjugation to the liposomal surface allows targeting to specific tissues - such liposomes are called immunoliposomes. Analogously to fluorophores, high concentrations of spin probes exhibit "self-quenching", a phenomenon where spectral signals are greatly attenuated at high concentration. Thus, spin probes encapsulated in immunoliposomes - at high concentration - are spectroscopically "dark". Immunoliposome endocytosis by tumor cells leads to liposomal degradation, releasing the spin probes, which become diluted in the intracellular volume. This dilution relieves self-quenching, restoring the spin probe's spectral signal, making the tumor appear "bright," and thus highlighted in EPRI. This thesis details the development of an immunoliposome delivery system for targeting spin probes to HER2-overexpresing xenograft tumors in mice. Specifically, this research demonstrates: 1) the development of an anti-HER2 single-chain antibody (scFv) for streamlined production of immunoliposomes; 2) the efficacy of fusogenic INF7 peptide for mediating endosome-to-cytosol delivery of immunoliposome-encapsulated imaging probes, which minimizes tumor cell probe extrusion; 3) the efficacy of adding multiple ionic charges to imaging probes to prolong cell retention. As a result of these enhancements, we hope to produce better signal buildup and retention in the tumor, thus improving the signal-to-noise ratio in imaging.
    Description
    University of Maryland, Baltimore. Molecular Medicine. Ph.D. 2017
    Keyword
    electron paramagnetic resonance imaging
    immunoliposome
    nitroxides
    targeted delivery
    Tumors
    Liposomes
    Neoplasms
    Identifier to cite or link to this item
    http://hdl.handle.net/10713/7353
    Collections
    Theses and Dissertations School of Medicine
    Theses and Dissertations All Schools

    entitlement

     
    DSpace software (copyright © 2002 - 2023)  DuraSpace
    Quick Guide | Policies | Contact Us | UMB Health Sciences & Human Services Library
    Open Repository is a service operated by 
    Atmire NV
     

    Export search results

    The export option will allow you to export the current search results of the entered query to a file. Different formats are available for download. To export the items, click on the button corresponding with the preferred download format.

    By default, clicking on the export buttons will result in a download of the allowed maximum amount of items.

    To select a subset of the search results, click "Selective Export" button and make a selection of the items you want to export. The amount of items that can be exported at once is similarly restricted as the full export.

    After making a selection, click one of the export format buttons. The amount of items that will be exported is indicated in the bubble next to export format.