Intracellular Hyperthermia Mediated by Nanoparticles in Radiofrequency Fields in the Treatment of Pancreatic Cancer

Persistent Link:
http://hdl.handle.net/10150/222840
Title:
Intracellular Hyperthermia Mediated by Nanoparticles in Radiofrequency Fields in the Treatment of Pancreatic Cancer
Author:
Glazer, Evan S.
Issue Date:
2012
Publisher:
The University of Arizona.
Rights:
Copyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.
Abstract:
Intracellular hyperthermic therapy may prove to be a unique and novel approach to the management of pancreatic cancer. Utilizing the principle of photothermal destruction, selective killing of cancer cells with minimal injury to normal tissues may be possible. This dissertation investigated the role of antibody targeted metal nanoparticles and the cytotoxic effects of nonionizing radiofrequency fields in pancreatic cancer. Cancer cell death was induced by heat release from intracellular metal nanoparticles after radiofrequency field exposure. Fluorescent and gold nanoparticles were delivered with two antibodies, cetuximab and PAM-4, to pancreatic cancer cells in vitro and mouse xenografts in vivo. Selective delivery of these nanoparticles induced cell death in vitro and decreased tumor burden in vivo after whole animal RF field exposure. This occurred through both apoptosis and necrosis. In addition, activated caspase-3 was increased after antibody treatment and RF field exposure. Furthermore, although there was non-specific uptake by the liver and spleen in vivo, there was no evidence of acute or chronic toxicity in the animals. These results are in agreement with the principle that malignant cells are more thermally sensitive than normal cells or tissues. Selective intracellular delivery of metal nanoparticles coupled with whole body RF field exposure may be a beneficial therapy against micrometastases and unresectable pancreatic cancer in the future. Further studies are planned with more specific antibodies, other nanoparticles, and other cancer targets.
Type:
text; Electronic Dissertation
Keywords:
radiation; radiofrequency field; Medical Sciences; nanoparticles; pancreatic cancer
Degree Name:
Ph.D.
Degree Level:
doctoral
Degree Program:
Graduate College; Medical Sciences
Degree Grantor:
University of Arizona
Advisor:
Krouse, Robert S.

Full metadata record

DC FieldValue Language
dc.language.isoenen_US
dc.titleIntracellular Hyperthermia Mediated by Nanoparticles in Radiofrequency Fields in the Treatment of Pancreatic Canceren_US
dc.creatorGlazer, Evan S.en_US
dc.contributor.authorGlazer, Evan S.en_US
dc.date.issued2012-
dc.publisherThe University of Arizona.en_US
dc.rightsCopyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.en_US
dc.description.abstractIntracellular hyperthermic therapy may prove to be a unique and novel approach to the management of pancreatic cancer. Utilizing the principle of photothermal destruction, selective killing of cancer cells with minimal injury to normal tissues may be possible. This dissertation investigated the role of antibody targeted metal nanoparticles and the cytotoxic effects of nonionizing radiofrequency fields in pancreatic cancer. Cancer cell death was induced by heat release from intracellular metal nanoparticles after radiofrequency field exposure. Fluorescent and gold nanoparticles were delivered with two antibodies, cetuximab and PAM-4, to pancreatic cancer cells in vitro and mouse xenografts in vivo. Selective delivery of these nanoparticles induced cell death in vitro and decreased tumor burden in vivo after whole animal RF field exposure. This occurred through both apoptosis and necrosis. In addition, activated caspase-3 was increased after antibody treatment and RF field exposure. Furthermore, although there was non-specific uptake by the liver and spleen in vivo, there was no evidence of acute or chronic toxicity in the animals. These results are in agreement with the principle that malignant cells are more thermally sensitive than normal cells or tissues. Selective intracellular delivery of metal nanoparticles coupled with whole body RF field exposure may be a beneficial therapy against micrometastases and unresectable pancreatic cancer in the future. Further studies are planned with more specific antibodies, other nanoparticles, and other cancer targets.en_US
dc.typetexten_US
dc.typeElectronic Dissertationen_US
dc.subjectradiationen_US
dc.subjectradiofrequency fielden_US
dc.subjectMedical Sciencesen_US
dc.subjectnanoparticlesen_US
dc.subjectpancreatic canceren_US
thesis.degree.namePh.D.en_US
thesis.degree.leveldoctoralen_US
thesis.degree.disciplineGraduate Collegeen_US
thesis.degree.disciplineMedical Sciencesen_US
thesis.degree.grantorUniversity of Arizonaen_US
dc.contributor.advisorKrouse, Robert S.en_US
dc.contributor.committeememberCurley, Steven A.en_US
dc.contributor.committeememberMcDonagh, Paul F.en_US
dc.contributor.committeememberHeimark, Ronald L.en_US
dc.contributor.committeememberFriese, Randallen_US
dc.contributor.committeememberKrouse, Robert S.en_US
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