Intracellular Transport in Cancer Treatments: Carbon Nanohorns Conjugated to Quantum Dots and Chemotherapeutic Agents

dc.contributor.authorZimmermann, Kristen Annen
dc.contributor.committeecochairRylander, Christopher G.en
dc.contributor.committeecochairRylander, M. Nicholeen
dc.contributor.committeememberLong, Timothy E.en
dc.contributor.departmentBiomedical Engineeringen
dc.date.accessioned2016-09-22T14:56:39Zen
dc.date.adate2012-06-05en
dc.date.available2016-09-22T14:56:39Zen
dc.date.issued2012-04-26en
dc.date.rdate2015-04-22en
dc.date.sdate2012-05-10en
dc.description.abstractCancer therapies are often limited by bulk and cellular barriers to transport. Nanoparticle or chemotherapeutic compound intracellular transport has implications in understanding therapeutic effect and toxicity. The scope of this thesis was to study the intracellular transport of carbon nanohorns and to improve the efficacy of various chemotherapeutic agents through increased intracellular transport. In the first study, fluorescent probes (quantum dots) were conjugated to carbon nanohorns to facilitate the optical visualization of the nanohorns. These hybrid particles were characterized with transmission electron microscopy, electron dispersive spectroscopy and UV-VIS/FL spectroscopy. Their cellular uptake kinetics, uptake efficiencies, and intracellular distribution were determined in three malignant cell lines (breast – MDA-MB-231, bladder – AY-27, and brain – U87-MG) using flow cytometry and confocal microscopy. Intracellular distribution did not vary greatly between cell lines; however, the uptake kinetics and efficiencies were highly dependent on cell morphology. In the second study, the efficacy of various chemotherapeutic agents (i.e., doxorubicin, cisplatin, and carboplatin) was evaluated in AY-27 rat bladder transitional cell carcinoma cells. In the future, severe hyperthermia and chemothermotherapy (chemotherapy + hyperthermia) will also be evaluated. Doxorubicin and cisplatin compounds were more toxic compared to carboplatin. Hyperthermia has previously shown to increase the cellular uptake of chemotherapeutic agents; therefore, chemothermotherapy is expected to have synergistic effects on cell death. This work can then be translated to carbon nanohorn-based laser heating to generate thermal energy in a local region for delivery of high concentrations of chemotherapeutic agents. Although these two concepts are small pieces of the overall scope of nanoparticle-based therapies, they are fundamental to the advancement of such therapies.en
dc.description.degreeMaster of Scienceen
dc.identifier.otheretd-05102012-130107en
dc.identifier.sourceurlhttp://scholar.lib.vt.edu/theses/available/etd-05102012-130107/en
dc.identifier.urihttp://hdl.handle.net/10919/72986en
dc.language.isoen_USen
dc.publisherVirginia Techen
dc.rightsIn Copyrighten
dc.rights.urihttp://rightsstatements.org/vocab/InC/1.0/en
dc.subjectCanceren
dc.subjectIntracellular distributionen
dc.subjectcarbon nanohornen
dc.subjectcellular uptake kineticsen
dc.subjectchemotherapyen
dc.subjecthyperthermiaen
dc.subjectquantum doten
dc.subjecttransporten
dc.titleIntracellular Transport in Cancer Treatments: Carbon Nanohorns Conjugated to Quantum Dots and Chemotherapeutic Agentsen
dc.typeThesisen
dc.type.dcmitypeTexten
thesis.degree.disciplineBiomedical Engineeringen
thesis.degree.grantorVirginia Polytechnic Institute and State Universityen
thesis.degree.levelmastersen
thesis.degree.nameMaster of Scienceen

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