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  • March 21, 2019
  • Kim, Junghyun
    • Affiliation: Eshelman School of Pharmacy, Division of Pharmacoengineering and Molecular Pharmaceutics
  • The importance of developing better cancer therapeutics cannot be over-emphasized. Among several approaches for improving patient outcome and satisfaction, targeted drug delivery has gained a lot of attention as a solution to maximizing therapeutic efficacy and minimizing the off-target side effects. Although there have been tremendous improvements in delivering chemotherapeutics using nanocarriers for achieving targeted drug delivery, reports on the use of this strategy for delivering therapeutic radionuclides are scarce. Considering the fact that radiation therapy is a standard of care for about half of all cancer patients, there is much evidence that more advancements are needed in the field of targeted delivery of therapeutic radionuclides. In this dissertation, with the goal of delivering targeted radiation to cancer, a neutron-activation approach was exploited for producing therapeutic radionuclides with minimum handling of highly radioactive substances. Various material matrices were explored for this strategy. In Chapter 1, three different types of radiation therapy – external beam radiation therapy, internal radiation therapy and systemic radiation therapy – along with neutron-activatable radionuclides and the rationale for proper isotope selection – were discussed. Additionally, carbon nanomaterials which have drawn great interest in numerous research fields for decades were thoroughly reviewed with a focus on biomedical applications in order to introduce the versatility of these materials. Among carbon-based matrices, graphene oxide nanoplatelets (GONs) and mesoporous carbon nanoparticles (MCNs) were chosen and examined for their application to systemic radiation therapy. In Chapter 2, GONs that were designed so that they would not leach neutron-activated radionuclides in normal tissues but would selectively release their radioactive cargo in the tumor microenvironment are described. MCNs possessing a more uniform size and shape were investigated as a carrier for the stable isotope 165Ho are presented in Chapter 3. To achieve complete prevention of holmium leaching, the synthesis of holmium oxide in the pores of MCNs was employed, and this resulted in the MCNs maintaining their structural integrity with almost no holmium leaching after a prolonged neutron irradiation time (10 h). As an extension of this neutron-activation technology using radioactive needles that mimicked the microneedle technology adopted in transdermal drug delivery was developed for internal radiation therapy is described in Chapter 4. The ultimate goal of this work was to deliver high doses of targeted radiation directly into solid tumors by insertion of the radioactive needles. As a means to replace current radiation applicators used in the treatment of some solid tumors, custom-sized titanium and molybdenum needles were prepared as base materials. Neutron-activatable radionuclides (holmium and rhenium) were coated on the surface of these needles by pulsed laser deposition and chemical vapor deposition. The stability of the coatings under physiological-mimicking conditions as well as after neutron irradiation was extensively evaluated. In summary, carbon-based nanocarriers and solid needles containing or coated with neutron-activatable elements were demonstrated to be very suitable for use in radiation therapy. Irradiation of these matrices in a neutron flux produced therapeutic amounts of radiation without affecting their physical integrity.
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Rights statement
  • In Copyright
  • Matthew, Matthew
  • Hingtgen, Shawn
  • Jay, Michael
  • Lai, Samuel
  • Ainslie, Kristy
  • Doctor of Philosophy
Degree granting institution
  • University of North Carolina at Chapel Hill
Graduation year
  • 2017

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