Modulation of nanoparticle uptake, intracellular distribution, and retention with docetaxel to enhance radiotherapy

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dc.contributor.author Bannister, Aaron
dc.date.accessioned 2019-12-10T23:42:10Z
dc.date.copyright 2019 en_US
dc.date.issued 2019-12-10
dc.identifier.uri http://hdl.handle.net/1828/11355
dc.description.abstract OBJECTIVE: One of the major issues in current radiotherapy (RT) is the normal tissue toxicity. A smart combination of agents within the tumor would allow lowering the RT dose required while minimizing the damage to healthy tissue surrounding the tumor. We chose gold nanoparticles (GNPs) and docetaxel (DTX) as our choice of two radiosensitizing agents. They have a different mechanism of action which could lead to synergistic effect. Our first goal was to assess the variation in GNP uptake, distribution, and retention in the presence of DTX. Our second goal was to assess the therapeutic results of the triple combination, RT/GNPs/DTX. METHODS: We used HeLa and MDA-MB-231 cells for our study. Cells were incubated with GNPs (0.2nM) in the absence and presence of DTX (50nM) for 24 hrs for determination of uptake, distribution, and retention of NPs. For RT experiment, treated cells were given a 2 Gy dose of 6 MV photons using a linear accelerator. RESULTS: Concurrent treatment of DTX and GNPs resulted in over 85% retention of GNPs in tumor cells. DTX treatment also forced GNPs to be closer to the most important target, the nucleus, resulting in a significant decrease in cell survival with the triple combination of RT, GNPs, and DTX vs. RT plus DTX alone. Our experimental therapeutics results are supported by Monte Carlo simulations. CONCLUSION: The ability to not only trap GNPs at clinically feasible doses but also to retain them within the cells could lead to meaningful fractionated treatments in future combined cancer therapy. Furthermore, the suggested triple combination of RT/GNPs/DTX may allow lowering the RT dose to spare surrounding healthy tissue. ADVANCES IN KNOWLEDGE: This is the first study to show intracellular GNP transport disruption by DTX, and its advantage in radiosensitization. en_US
dc.language English eng
dc.language.iso en en_US
dc.rights Available to the World Wide Web en_US
dc.subject gold nanoparticle en_US
dc.subject nanoparticle en_US
dc.subject cancer en_US
dc.subject docetaxel en_US
dc.subject taxotere en_US
dc.subject radiotherapy en_US
dc.subject endocytosis en_US
dc.subject exocytosis en_US
dc.subject microtubule en_US
dc.title Modulation of nanoparticle uptake, intracellular distribution, and retention with docetaxel to enhance radiotherapy en_US
dc.type Thesis en_US
dc.contributor.supervisor Chithrani, Devika
dc.degree.department Department of Physics and Astronomy en_US
dc.degree.level Master of Science M.Sc. en_US
dc.description.scholarlevel Graduate en_US
dc.description.embargo 2020-10-31

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