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dc.contributor.authorSuh, SeungBeumen_US
dc.date.accessioned2019-02-09T07:00:38Z
dc.date.available2019-02-09T07:00:38Z
dc.date.issued2017-08-17
dc.identifier.othervt_gsexam:12294en_US
dc.identifier.urihttp://hdl.handle.net/10919/87560
dc.description.abstractSystemic chemotherapy is a major therapeutic approach for nearly all types and stages of cancer. Success of this treatment depends not only on the efficacy of the therapeutics but also on the transport of the drug to all tumor cells in sufficient concentrations. Intratumoral drug transport is limited by characteristics of the tumor microenvironment such as elevated interstitial pressure and sparse, irregular vascularization. Moreover, poor tumor selectivity, leads to systemic toxicity. Bacteria possess a host of characteristics that address the aforementioned challenges in conventional drug delivery approaches including tumor selectivity, preferential tumor colonization, effective tumor penetration, which can be augmented via genetic engineering. However, in clinical trials conducted to date, bacteria have rarely been able to inhibit tumor growth solely by their presence in the tumor. The overall goal of this doctoral dissertation is to develop a novel tumor treatment system based on Salmonella Typhimurium VNP20009 (genetically modified for preferential tumor colonization and attenuation) coupled with biodegradable copolymer, poly(lactic-co-glycolic acid) nanoparticles, hereafter referred to as NanoBEADS (Nanoscale Bacteria Enabled Autonomous Drug Delivery System). To this end, a NanoBEADS fabrication procedure that is robust and repeatable was established and a microfluidic chemotaxis-based sorting platform for the separation NanoBEADS from unattached nanoparticles was developed. The transport efficacy of NanoBEADS compared to the commonly used passively-diffusing nanoparticle was investigated in vitro and in vivo and the intratumoral penetration of the therapeutic vectors was quantified using a custom image processing algorithm. The mechanism of intratumoral penetration was elucidated through 2D and 3D invasion assays. Lastly, we developed a biophysical model of intratumoral transport of NanoBEADS based on the intratumoral penetration experimental results towards the theoretical evaluation of the drug transport profile following the administration of NanoBEADS.en_US
dc.format.mediumETDen_US
dc.publisherVirginia Techen_US
dc.rightsThis item is protected by copyright and/or related rights. Some uses of this item may be deemed fair and permitted by law even without permission from the rights holder(s), or the rights holder(s) may have licensed the work for use under certain conditions. For other uses you need to obtain permission from the rights holder(s).en_US
dc.subjectTumor targeting bacteriaen_US
dc.subjectCancer treatmenten_US
dc.subjectBio-hybrid microroboticsen_US
dc.titleBacteria-Enabled Autonomous Drug Delivery Systems: Development, Characterization of Intratumoral Transport and Modelingen_US
dc.typeDissertationen_US
dc.contributor.departmentMechanical Engineeringen_US
dc.description.degreePHDen_US
thesis.degree.namePHDen_US
thesis.degree.leveldoctoralen_US
thesis.degree.grantorVirginia Polytechnic Institute and State Universityen_US
thesis.degree.disciplineMechanical Engineeringen_US
dc.contributor.committeechairBehkam, Baharehen_US
dc.contributor.committeememberBattaglia, Francineen_US
dc.contributor.committeememberDervisis, Nikolaosen_US
dc.contributor.committeememberTafti, Danesh Ken_US
dc.contributor.committeememberScharf, Birgiten_US


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