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DonaldEPryor PhD Dissertation.pdf (3.4 MB)

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Synthesis and Bioactivity Studies of Nanoparticles Based on Simple Inorganic and Coordination Gallium Compounds as Cellular Delivering Vehicles of Ga(III) Ions for Potential Therapeutic Applications

Pryor, Donald Edward
http://rave.ohiolink.edu/etdc/view?acc_num=kent1543554532063877

Abstract Details

2018, PHD, Kent State University, College of Arts and Sciences / Department of Chemistry and Biochemistry.
Iron plays an irreplaceable role in the cell and is found in numerous proteins that use iron as a biological catalyst to perform cell maintenance, growth and cell division. In tumor cells, as well as in normal cellular proliferation, there is a dependence on iron and its availability. With the recognized need to create and test new anti-tumor agents, utilizing the fact that cancer cells disproportionately tend to take up greater amounts of iron than do normal cells, this allows a pathway to be exploited using other metals such as gallium that can interfere in iron metabolism. Gallium ion possesses unique medicinal properties due to its resemblance to iron and is a known mimic of this essential metal. Therefore showing promise for treatment of a variety of diseases and disorders, particularly cancer and bacterial infection due to its antitumorigenic properties and antimicrobial activity. Use of simple soluble inorganic gallium salts, represented by Ganite® for treating a variety of diseases have already reached clinical applications. However, there are still several drawbacks of using gallium salts to deliver gallium at the cellular level, including (1) low-transport capacity of gallium because of the limited plasma concentrations of apo-Tf available for Ga(III)-binding in the blood stream; (2) slow kinetics due to the need to recycle the Tf after the Ga(III) ion is delivered inside the cell; and (3) hydrolysis of Ga(III) ions is a concentration-limiting factor and the origin of renal toxicity of drugs based on soluble gallium salts. To circumvent these limitations of the transferrin-receptor mediated uptake. Gallium nanoparticles with pH sensitivity are synthesized on a PVP (polyvinylpyrrolidone) template for cell culture viability studies on various cancer cell lines. Three gallium-based nanoparticle systems are synthesized and investigated here which confirm cellular uptake in tumorigenic cells and/or cytotoxicity to tumor cells. Effectively bypassing the limited gallium ion concentration uptake possible with simple gallium salts. These inorganic gallium-based nanoparticles show some success here and need for future exploration. Finally, the need for new antibacterial agents are as necessary as is the need for new cancer therapeutics. Since gallium salts have known bacterial cytotoxicity facing some of the aforementioned limitations, a fourth organo-metallic complex prone to bacterial uptake is derived from a synthesis with gallium metal, lawsone and bipyridine; all later attached to a biological compatible polymer (PVP) that is then tested in bacterial cells of Gram - (negative) and Gram + (positive) species and then in a mammalian cell line called RAW 264.7, demonstrating a therapeutic window of opportunity to provide dual cytotoxicity to both Gram positive and Gram negative bacteria while hardly affecting this mammalian cell line. These are the first novel gallium nanoparticles of these types.
Songping Huang (Advisor)
Bansidhar Datta (Committee Member)
Mietek Jaroniec (Committee Member)
Robin Selinger (Committee Co-Chair)
Qi-Huo Wei (Committee Member)
171 p.
Biochemistry; Cellular Biology; Chemical Engineering; Chemistry
Gallium; Iron; Gallium Chemistry; Nano-particles; Cancer; Transferrin; Transferrin Receptor; Cell Culture Studies; Inorganic Synthesis; Nanomaterials; Tumors; Gram Negative Bacteria; Gram Positive Bacteria; Lawsone, PVP; Organic Synthesis; Cytotoxicity

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Citations

  • Pryor, D. E. (2018). Synthesis and Bioactivity Studies of Nanoparticles Based on Simple Inorganic and Coordination Gallium Compounds as Cellular Delivering Vehicles of Ga(III) Ions for Potential Therapeutic Applications [Doctoral dissertation, Kent State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=kent1543554532063877

    APA Style (7th edition)

  • Pryor, Donald. Synthesis and Bioactivity Studies of Nanoparticles Based on Simple Inorganic and Coordination Gallium Compounds as Cellular Delivering Vehicles of Ga(III) Ions for Potential Therapeutic Applications. 2018. Kent State University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=kent1543554532063877.

    MLA Style (8th edition)

  • Pryor, Donald. "Synthesis and Bioactivity Studies of Nanoparticles Based on Simple Inorganic and Coordination Gallium Compounds as Cellular Delivering Vehicles of Ga(III) Ions for Potential Therapeutic Applications." Doctoral dissertation, Kent State University, 2018. http://rave.ohiolink.edu/etdc/view?acc_num=kent1543554532063877

    Chicago Manual of Style (17th edition)

kent1543554532063877
516
© 2018, all rights reserved.
This open access ETD is published by Kent State University and OhioLINK.