Protein Nanoscaffolds for Delivering Toxic Inorganic Cargo to Cancer Cells

dc.contributor.advisorKurtz, Donald M.
dc.contributor.authorCioloboc, Daniela
dc.contributor.committeeMemberGoins, Beth
dc.contributor.committeeMemberFrantz, Doug E.
dc.contributor.committeeMemberMcHardy, Stanton
dc.contributor.committeeMemberNash, Kelly
dc.contributor.committeeMemberTonzetich, Zachary J.
dc.date.accessioned2024-02-09T20:20:40Z
dc.date.available2024-02-09T20:20:40Z
dc.date.issued2017
dc.descriptionThis item is available only to currently enrolled UTSA students, faculty or staff. To download, navigate to Log In in the top right-hand corner of this screen, then select Log in with my UTSA ID.
dc.description.abstractTargeted delivery of anticancer drugs or prodrugs to tumors can minimize systemic toxicity and side effects. This study develops platforms for targeted delivery of two potentially less systemically toxic prodrugs by exploiting the native and/or bioinorganic properties of two ferritins, both of which function naturally as iron storage proteins. Two delivery approaches were investigated. The first system was designed to serve as either an enhancement or alternative to traditional photodynamic therapy by generating hydroxyl radical in addition to singlet oxygen as the toxic reactive oxygen species. This system used Escherichia coli bacterioferritin (Bfr) loaded with ~2,500 irons and multiple zinc-porphyrin (ZnP) photosensitizers. Ferrous iron was released by photoreduction of ferric iron stored within the Bfr protein shell. Hydroxyl radicals were generated via the Fenton reaction between hydrogen peroxide and the released ferrous iron. The outer surface of the Bfr protein shell was coated with peptides that specifically bind to a receptor known to be overexpressed in many tumor cells and tumor vasculature. The iron-loaded peptide-ZnP-Bfr was endocytosed by melanoma cells, where it showed photo-triggered release of iron and light-dependent cytotoxicity. The second system, built around human heavy chain ferritin (HFn), was loaded with arsenate as a less toxic “prodrug” and designed to release arsenic in its toxic, therapeutically effective reduced form, arsenic trioxide (ATO). The Hfn shell was coated with peptides targeting receptors that are hyperexpressed in triple negative breast cancers. The arsenate/iron-loaded-Hfn was endocytosed by a breast cancer cell line and showed cytotoxicity equivalent to that of free ATO on an arsenic basis, whereas the “empty” or iron-only loaded Hfn showed no cytotoxicity. Although HFn has previously been used to deliver organic drugs and imaging agents, these new results demonstrate that both Bfr and HFn can be manipulated to function as 'Trojan horse’ nanocarriers for inorganic drugs.
dc.description.departmentChemistry
dc.format.extent147 pages
dc.format.mimetypeapplication/pdf
dc.identifier.isbn9780355533729
dc.identifier.urihttps://hdl.handle.net/20.500.12588/3240
dc.languageen
dc.subjectarsenic
dc.subjectFenton reactive iron
dc.subjectnanocarriers
dc.subjectphotodynamic therapy
dc.subjectTargeted delivery
dc.subject.classificationBiochemistry
dc.subject.classificationMedicine
dc.subject.classificationNanoscience
dc.titleProtein Nanoscaffolds for Delivering Toxic Inorganic Cargo to Cancer Cells
dc.typeThesis
dc.type.dcmiText
dcterms.accessRightspq_closed
thesis.degree.departmentChemistry
thesis.degree.grantorUniversity of Texas at San Antonio
thesis.degree.levelDoctoral
thesis.degree.nameDoctor of Philosophy

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