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Synthesis and Application of Polymer Stabilized, Water Dispersible Copper Based Nanoparticles as Anti-cancer and Diagnostic Agents

YARABARLA, SRIRAMAKRISHNA
http://rave.ohiolink.edu/etdc/view?acc_num=kent1492608832326

Abstract Details

2017, PHD, Kent State University, College of Arts and Sciences / Department of Chemistry.
The objectives of this dissertation work are twofold. The first of the two is to evaluate the anti-cancer properties of a series of copper based NP systems rationally designed and synthesized via aqueous route utilizing simple salt metathesis reactions in the presence of biocompatible polymer. The acquired resistance of cancer cells to conventional molecular drugs such as cisplatin and doxorubicin presents simultaneously both opportunities and challenges to chemists to develop novel and more effective anti-cancer agents. While many known NPs, both inorganic and organic/polymeric are reported for drug delivery applications, the inherent capability of the copper based NPs as anti-cancer agents is relatively less explored. Further, there is lack of systematic study to evaluate the behavior of these NPs under the conditions pertaining to physiological and tumor intracellular and extracellular milieu. The utility of the proposed NPs in my dissertation is based on the hypothesis that copper-based NPs elevate the production of ROS to unsustainable levels in cancer cells through surface copper mediated Fenton-like chemistry that generates free radicals thereby inducing the cancer cell death. The second objective is to explore the same NP systems for diagnostic purposes at a much lower concentration window as potential imaging agents for positron emission tomography (PET). The nuclide Cu-64 is a positron-emitting radioisotope and owing to its favorable decay characteristics is being extensively studied for its application in PET imaging. This area is predominantly comprised of copper-64 chelate complexes based on macrocyclic ligands. Hitherto, the main focus of many such studies is devoted to the development of suitable macrocyclic chelators, more recently as bifunctional chelators, to impart kinetic and thermodynamic stability to the metal-chelate complexes. Numerous studies have shown that these copper chelate complexes suffer from copper exchange with biomolecules in vivo via `transchelation'. Although studies utilizing Cu-64 labelled NPs have begun just less than a decade, the radioisotope is linked to these NPs through the certain chelate ligands that are chemically conjugated to the surface of NPs. These NPs suffer from the drawbacks, namely detachment of the radionuclide-chelator complex from the NP surface or the displacement of radionuclide via transchelation or both. Alternatively, copper-based NPs for eg. copper Prussian blue analog NPs, copper tetrathiomolybdate NPs etc. can provide kinetic and thermodynamic stability, and thus eliminating the aforementioned limitations associated with chelator-based systems. Additionally, such NPs inherently possess high loading of specific activity and can act as better and sensitive imaging agents. However, to the best of our knowledge only one copper-based NPs ie. CuS NPs that incorporated Cu-64 isotope within the NPs is reported. In our last project, we also explored a nanoparticulate system of copper and manganese based Prussian blue analog as a single agent for theranostic purposes. Developed through a facile one-step reaction, this novel intrinsically capable PBA nanoplatform functions as a theranostic agent with magnetic relaxivity features on a par with commercial Gd-chelate based MRI contrast agents.
Songping Huang, PhD (Advisor)
Scott Bunge, PhD (Committee Member)
Mietek Jaroniec, PhD (Committee Member)
Gail Fraizer, PhD (Committee Member)
Torsten Hegmann, PhD (Committee Member)
209 p.
Chemistry; Nanoscience
Nanoparticles; copper tetrathiomolybdate; copper hydroxyphosphate; Libethenite; Prussian blue analog; anti-cancer; PET; MRI contrast agent; theranostic agents

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Citations

  • YARABARLA, S. (2017). Synthesis and Application of Polymer Stabilized, Water Dispersible Copper Based Nanoparticles as Anti-cancer and Diagnostic Agents [Doctoral dissertation, Kent State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=kent1492608832326

    APA Style (7th edition)

  • YARABARLA, SRIRAMAKRISHNA. Synthesis and Application of Polymer Stabilized, Water Dispersible Copper Based Nanoparticles as Anti-cancer and Diagnostic Agents . 2017. Kent State University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=kent1492608832326.

    MLA Style (8th edition)

  • YARABARLA, SRIRAMAKRISHNA. "Synthesis and Application of Polymer Stabilized, Water Dispersible Copper Based Nanoparticles as Anti-cancer and Diagnostic Agents ." Doctoral dissertation, Kent State University, 2017. http://rave.ohiolink.edu/etdc/view?acc_num=kent1492608832326

    Chicago Manual of Style (17th edition)

kent1492608832326
902
© 2017, all rights reserved.
This open access ETD is published by Kent State University and OhioLINK.