Bioengineered Nanoparticles for Targeted Cancer Therapy

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dc.contributor.advisorVishwanatha, Jamboor K.
dc.contributor.committeeMemberRanjan, Amalendu P.
dc.contributor.committeeMemberCistola, David P.
dc.contributor.committeeMemberOlivencia-Yurvati, Albert H.
dc.creatorGdowski, Andrew S.
dc.date.accessioned2020-06-01T14:02:36Z
dc.date.available2020-06-01T14:02:36Z
dc.date.issued2018-05
dc.description.abstractDespite improved overall survival in cancer patients over the past 50 years, limited advances have been made in treating patients with metastatic cancers. Multiple types of cancers demonstrate the unique ability to specifically metastasize to the bone. Among these, prostate cancer exhibits increased capacity to create bone specific lesions with high frequency. Once bone localization takes place, treatment regimens are limited and overall survival is poor. These bone metastases often cause debilitating and life threatening problems including: uncontrollable pain, hypercalcemia, broken bones, spinal cord compression, and the inability to perform activities of daily living. The overarching goal of this thesis was to develop novel bone targeted nanoparticle therapies. The first generation of nanoparticles we engineered and tested were designed to target the hydroxyapatite structure of the bone particularly in areas of high bone turnover with subsequent therapeutic release at the site of the tumor. Notably, this nanoparticle formulation was efficacious in decreasing prostate cancer bone metastatic tumors, improving bone structure, and reducing pain in a mouse model. The next generation of nanoparticles were developed to simultaneously target the bone endothelium and tumor cells using a programmable bioinspired approach with guidance from genomic information of prostate cancer patients. This novel bioinspired nanoparticle demonstrated enhanced ability to self-recognize cancer cells as well as improved bone homing and retention in our in vivo evaluation. Finally, we addressed the challenge of nanoparticle manufacturing scale up from lab size quantities to large scale batches using a microfluidic process. It is our sincere hope that concepts and publications derived from this thesis will help guide future efforts for targeted therapy and improve the lives of patients with cancer.
dc.format.mimetypeapplication/pdf
dc.identifier.urihttps://hdl.handle.net/20.500.12503/29844
dc.language.isoen
dc.subjectbone metastasis
dc.subjectnanoparticles
dc.subjectprostate cancer
dc.titleBioengineered Nanoparticles for Targeted Cancer Therapy
dc.typeThesis
dc.type.materialtext
thesis.degree.departmentGraduate School of Biomedical Sciences
thesis.degree.disciplineBiomedical Sciences
thesis.degree.grantorUniversity of North Texas Health Science Center at Fort Worth
thesis.degree.nameDoctor of Philosophy

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