ingest cdrApp 2017-08-15T20:52:51.509Z d91e81c8-5a8a-4e8a-976c-cad4e396e5ee modifyDatastreamByValue RELS-EXT fedoraAdmin 2017-08-15T20:53:26.123Z Setting exclusive relation modifyDatastreamByValue RELS-EXT fedoraAdmin 2017-08-15T20:53:35.182Z Setting exclusive relation addDatastream MD_TECHNICAL fedoraAdmin 2017-08-15T20:53:44.482Z Adding technical metadata derived by FITS modifyDatastreamByValue RELS-EXT fedoraAdmin 2017-08-15T20:53:54.153Z Setting exclusive relation addDatastream MD_FULL_TEXT fedoraAdmin 2017-08-15T20:54:04.768Z Adding full text metadata extracted by Apache Tika modifyDatastreamByValue RELS-EXT fedoraAdmin 2017-08-15T20:54:22.948Z Setting exclusive relation modifyDatastreamByValue RELS-EXT cdrApp 2017-08-22T13:58:00.386Z Setting exclusive relation modifyDatastreamByValue MD_DESCRIPTIVE cdrApp 2017-11-29T19:27:09.814Z modifyDatastreamByValue MD_DESCRIPTIVE cdrApp 2018-01-25T19:28:47.149Z modifyDatastreamByValue MD_DESCRIPTIVE cdrApp 2018-01-27T19:00:45.426Z modifyDatastreamByValue MD_DESCRIPTIVE cdrApp 2018-02-28T20:54:22.138Z modifyDatastreamByValue MD_DESCRIPTIVE cdrApp 2018-03-14T16:52:22.209Z modifyDatastreamByValue MD_DESCRIPTIVE cdrApp 2018-05-18T19:10:51.259Z modifyDatastreamByValue MD_DESCRIPTIVE cdrApp 2018-07-11T15:38:23.093Z modifyDatastreamByValue MD_DESCRIPTIVE cdrApp 2018-07-18T11:13:08.940Z modifyDatastreamByValue MD_DESCRIPTIVE cdrApp 2018-08-21T20:01:38.618Z modifyDatastreamByValue MD_DESCRIPTIVE cdrApp 2018-09-27T21:07:25.848Z modifyDatastreamByValue MD_DESCRIPTIVE cdrApp 2018-10-12T11:20:43.140Z modifyDatastreamByValue MD_DESCRIPTIVE cdrApp 2018-10-17T16:39:18.677Z modifyDatastreamByValue MD_DESCRIPTIVE cdrApp 2019-03-21T21:40:14.457Z Junghyun Kim Author Pharmaceutical Sciences Program Eshelman School of Pharmacy NEUTRON-ACTIVATION OF MATERIAL MATRICES FOR PRODUCING THERAPEUTIC RADIONUCLIDES 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. Spring 2017 2017 Pharmaceutical sciences Biomedical engineering Health sciences Graphene Oxide Nanoplatelets, Holmium, Material Matrices, Mesoporous Carbon Nanoparticles, Neutron-Activatable Needles, Neutron Activation eng Doctor of Philosophy Dissertation University of North Carolina at Chapel Hill Graduate School Degree granting institution Pharmaceutical Sciences Michael Jay Thesis advisor Michael Jay Thesis advisor Kristy Ainslie Thesis advisor Samuel Lai Thesis advisor Shawn Hingtgen Thesis advisor Matthew Matthew Thesis advisor text Junghyun Kim Author Pharmaceutical Sciences Program Eshelman School of Pharmacy NEUTRON-ACTIVATION OF MATERIAL MATRICES FOR PRODUCING THERAPEUTIC RADIONUCLIDES 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. Spring 2017 2017 Pharmaceutical sciences Biomedical engineering Health sciences Graphene Oxide Nanoplatelets, Holmium, Material Matrices, Mesoporous Carbon Nanoparticles, Neutron-Activatable Needles, Neutron Activation eng Doctor of Philosophy Dissertation University of North Carolina at Chapel Hill Graduate School Degree granting institution Pharmaceutical Sciences Michael Jay Thesis advisor Kristy Ainslie Thesis advisor Samuel Lai Thesis advisor Shawn Hingtgen Thesis advisor Matthew Matthew Thesis advisor text Junghyun Kim Creator Pharmaceutical Sciences Program Eshelman School of Pharmacy NEUTRON-ACTIVATION OF MATERIAL MATRICES FOR PRODUCING THERAPEUTIC RADIONUCLIDES 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. Spring 2017 2017 Pharmaceutical sciences Biomedical engineering Health sciences Graphene Oxide Nanoplatelets, Holmium, Material Matrices, Mesoporous Carbon Nanoparticles, Neutron-Activatable Needles, Neutron Activation eng Doctor of Philosophy Dissertation University of North Carolina at Chapel Hill Graduate School Degree granting institution Pharmaceutical Sciences Michael Jay Thesis advisor Kristy Ainslie Thesis advisor Samuel Lai Thesis advisor Shawn Hingtgen Thesis advisor Matthew Matthew Thesis advisor text Junghyun Kim Creator Pharmaceutical Sciences Program Eshelman School of Pharmacy NEUTRON-ACTIVATION OF MATERIAL MATRICES FOR PRODUCING THERAPEUTIC RADIONUCLIDES 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. Spring 2017 2017 Pharmaceutical sciences Biomedical engineering Health sciences Graphene Oxide Nanoplatelets, Holmium, Material Matrices, Mesoporous Carbon Nanoparticles, Neutron-Activatable Needles, Neutron Activation eng Doctor of Philosophy Dissertation University of North Carolina at Chapel Hill Graduate School Degree granting institution Pharmaceutical Sciences Michael Jay Thesis advisor Kristy Ainslie Thesis advisor Samuel Lai Thesis advisor Shawn Hingtgen Thesis advisor Matthew Matthew Thesis advisor text Junghyun Kim Creator Division of Pharmacoengineering and Molecular Pharmaceutics Eshelman School of Pharmacy NEUTRON-ACTIVATION OF MATERIAL MATRICES FOR PRODUCING THERAPEUTIC RADIONUCLIDES 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. Spring 2017 2017 Pharmaceutical sciences Biomedical engineering Health sciences Graphene Oxide Nanoplatelets, Holmium, Material Matrices, Mesoporous Carbon Nanoparticles, Neutron-Activatable Needles, Neutron Activation eng Doctor of Philosophy Dissertation University of North Carolina at Chapel Hill Graduate School Degree granting institution Pharmaceutical Sciences Michael Jay Thesis advisor Kristy Ainslie Thesis advisor Samuel Lai Thesis advisor Shawn Hingtgen Thesis advisor Matthew Matthew Thesis advisor text Junghyun Kim Creator Division of Pharmacoengineering and Molecular Pharmaceutics Eshelman School of Pharmacy NEUTRON-ACTIVATION OF MATERIAL MATRICES FOR PRODUCING THERAPEUTIC RADIONUCLIDES 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. 2017-05 2017 Pharmaceutical sciences Biomedical engineering Health sciences Graphene Oxide Nanoplatelets, Holmium, Material Matrices, Mesoporous Carbon Nanoparticles, Neutron-Activatable Needles, Neutron Activation eng Doctor of Philosophy Dissertation University of North Carolina at Chapel Hill Graduate School Degree granting institution Pharmaceutical Sciences Michael Jay Thesis advisor Kristy Ainslie Thesis advisor Samuel Lai Thesis advisor Shawn Hingtgen Thesis advisor Matthew Matthew Thesis advisor text Junghyun Kim Creator Division of Pharmacoengineering and Molecular Pharmaceutics Eshelman School of Pharmacy NEUTRON-ACTIVATION OF MATERIAL MATRICES FOR PRODUCING THERAPEUTIC RADIONUCLIDES 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. 2017 Pharmaceutical sciences Biomedical engineering Health sciences Graphene Oxide Nanoplatelets, Holmium, Material Matrices, Mesoporous Carbon Nanoparticles, Neutron-Activatable Needles, Neutron Activation eng Doctor of Philosophy Dissertation University of North Carolina at Chapel Hill Graduate School Degree granting institution Pharmaceutical Sciences Michael Jay Thesis advisor Kristy Ainslie Thesis advisor Samuel Lai Thesis advisor Shawn Hingtgen Thesis advisor Matthew Matthew Thesis advisor text 2017-05 Junghyun Kim Creator Division of Pharmacoengineering and Molecular Pharmaceutics Eshelman School of Pharmacy NEUTRON-ACTIVATION OF MATERIAL MATRICES FOR PRODUCING THERAPEUTIC RADIONUCLIDES 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. 2017 Pharmaceutical sciences Biomedical engineering Health sciences Graphene Oxide Nanoplatelets, Holmium, Material Matrices, Mesoporous Carbon Nanoparticles, Neutron-Activatable Needles, Neutron Activation eng Doctor of Philosophy Dissertation University of North Carolina at Chapel Hill Graduate School Degree granting institution Pharmaceutical Sciences Michael Jay Thesis advisor Kristy Ainslie Thesis advisor Samuel Lai Thesis advisor Shawn Hingtgen Thesis advisor Matthew Matthew Thesis advisor text 2017-05 Junghyun Kim Creator Division of Pharmacoengineering and Molecular Pharmaceutics Eshelman School of Pharmacy NEUTRON-ACTIVATION OF MATERIAL MATRICES FOR PRODUCING THERAPEUTIC RADIONUCLIDES 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. 2017 Pharmaceutical sciences Biomedical engineering Health sciences Graphene Oxide Nanoplatelets, Holmium, Material Matrices, Mesoporous Carbon Nanoparticles, Neutron-Activatable Needles, Neutron Activation eng Doctor of Philosophy Dissertation University of North Carolina at Chapel Hill Graduate School Degree granting institution Pharmaceutical Sciences Michael Jay Thesis advisor Kristy Ainslie Thesis advisor Samuel Lai Thesis advisor Shawn Hingtgen Thesis advisor Matthew Matthew Thesis advisor text 2017-05 Junghyun Kim Creator Division of Pharmacoengineering and Molecular Pharmaceutics Eshelman School of Pharmacy NEUTRON-ACTIVATION OF MATERIAL MATRICES FOR PRODUCING THERAPEUTIC RADIONUCLIDES 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. 2017 Pharmaceutical sciences Biomedical engineering Health sciences Graphene Oxide Nanoplatelets, Holmium, Material Matrices, Mesoporous Carbon Nanoparticles, Neutron-Activatable Needles, Neutron Activation eng Doctor of Philosophy Dissertation Pharmaceutical Sciences Michael Jay Thesis advisor Kristy Ainslie Thesis advisor Samuel Lai Thesis advisor Shawn Hingtgen Thesis advisor Matthew Matthew Thesis advisor text 2017-05 University of North Carolina at Chapel Hill Degree granting institution Junghyun Kim Creator Division of Pharmacoengineering and Molecular Pharmaceutics Eshelman School of Pharmacy NEUTRON-ACTIVATION OF MATERIAL MATRICES FOR PRODUCING THERAPEUTIC RADIONUCLIDES 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. 2017 Pharmaceutical sciences Biomedical engineering Health sciences Graphene Oxide Nanoplatelets; Holmium; Material Matrices; Mesoporous Carbon Nanoparticles; Neutron-Activatable Needles; Neutron Activation eng Doctor of Philosophy Dissertation Pharmaceutical Sciences Michael Jay Thesis advisor Kristy Ainslie Thesis advisor Samuel Lai Thesis advisor Shawn Hingtgen Thesis advisor Matthew Matthew Thesis advisor text 2017-05 University of North Carolina at Chapel Hill Degree granting institution Junghyun Kim Creator Division of Pharmacoengineering and Molecular Pharmaceutics Eshelman School of Pharmacy NEUTRON-ACTIVATION OF MATERIAL MATRICES FOR PRODUCING THERAPEUTIC RADIONUCLIDES 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. 2017 Pharmaceutical sciences Biomedical engineering Health sciences Graphene Oxide Nanoplatelets, Holmium, Material Matrices, Mesoporous Carbon Nanoparticles, Neutron-Activatable Needles, Neutron Activation eng Doctor of Philosophy Dissertation University of North Carolina at Chapel Hill Graduate School Degree granting institution Pharmaceutical Sciences Michael Jay Thesis advisor Kristy Ainslie Thesis advisor Samuel Lai Thesis advisor Shawn Hingtgen Thesis advisor Matthew Matthew Thesis advisor text 2017-05 Junghyun Kim Creator Division of Pharmacoengineering and Molecular Pharmaceutics Eshelman School of Pharmacy NEUTRON-ACTIVATION OF MATERIAL MATRICES FOR PRODUCING THERAPEUTIC RADIONUCLIDES 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. 2017 Pharmaceutical sciences Biomedical engineering Health sciences Graphene Oxide Nanoplatelets, Holmium, Material Matrices, Mesoporous Carbon Nanoparticles, Neutron-Activatable Needles, Neutron Activation eng Doctor of Philosophy Dissertation Pharmaceutical Sciences Michael Jay Thesis advisor Kristy Ainslie Thesis advisor Samuel Lai Thesis advisor Shawn Hingtgen Thesis advisor Matthew Matthew Thesis advisor text 2017-05 University of North Carolina at Chapel Hill Degree granting institution Junghyun Kim Creator Division of Pharmacoengineering and Molecular Pharmaceutics Eshelman School of Pharmacy NEUTRON-ACTIVATION OF MATERIAL MATRICES FOR PRODUCING THERAPEUTIC RADIONUCLIDES 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. 2017 Pharmaceutical sciences Biomedical engineering Health sciences Graphene Oxide Nanoplatelets; Holmium; Material Matrices; Mesoporous Carbon Nanoparticles; Neutron-Activatable Needles; Neutron Activation eng Doctor of Philosophy Dissertation Michael Jay Thesis advisor Kristy Ainslie Thesis advisor Samuel Lai Thesis advisor Shawn Hingtgen Thesis advisor Matthew Matthew Thesis advisor text 2017-05 University of North Carolina at Chapel Hill Degree granting institution Kim_unc_0153D_17147.pdf uuid:21f12788-6d5f-41b7-ab9d-50bd93aea8fa proquest 2019-08-15T00:00:00 2017-06-11T01:20:04Z application/pdf 2723156 yes