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dc.contributor.advisorDelehanty, James Ben_US
dc.contributor.advisorStroka, Kimberly Men_US
dc.contributor.authorSangtani, Ajmeetaen_US
dc.date.accessioned2019-06-19T05:37:33Z
dc.date.available2019-06-19T05:37:33Z
dc.date.issued2019en_US
dc.identifierhttps://doi.org/10.13016/yzf9-1nt5
dc.identifier.urihttp://hdl.handle.net/1903/21917
dc.description.abstractSystemic drug delivery relies on repeated dosing of large concentrations of poorly targeted drug leading to off-target toxicity. Recently, nanoparticle (NP)-mediated drug delivery (NMDD) has been developed as an approach to overcome the limitations of traditional drug delivery. The unique size-dependent properties of NPs and their ability to augment the activity of attached/loaded cargos makes them attractive drug delivery vectors. NPs are classified into two categories (soft or hard depending on their material composition) and our understanding of how to load and control soft NP materials currently surpasses that of hard NPs. In this dissertation we seek to further our fundamental knowledge of hard NP-based drug delivery systems. In Aim 1 we utilize a quantum dot (QD)-cell uptake peptide complex as a central scaffold to append various responsive peptide-drug constructs in order to modulate the toxicity of one of the most widely used chemotherapeutics, doxorubicin. By doing a comparative study of four chemical linkages, we determine the role played by attachment chemistry in controlling drug release. In Aim 2, we utilize the knowledge gained from Aim 1 to develop a system capable of overcoming multidrug resistance in cancer cells, which is known to severely limit the efficacy of chemotherapeutics. Our hard NP conjugate system is unique as it is one of the few systems reported in the literature to bypass multidrug resistance pumps without the need for exogenous drugs. Finally, in Aim 3 we append a peptide for membrane targeting and a photosensitizing drug capable of generating reactive oxygen species to the QD. This multifunctional system displays augmented therapeutic efficacy of the appended photosensitizer by delivering it to the membrane of cells and controlling its actuation using energy transfer. The work described here details basic concepts for the design of “smart” hard NP materials for internally and externally-triggered, active release of surface-appended drug cargos. Additionally, we hope to elucidate the important design considerations that must be taken into account when designing hard NP systems for controlled drug delivery.en_US
dc.language.isoenen_US
dc.titleACTUATION OF MULTIFUNCTIONAL HARD NANOPARTICLES FOR ACTIVELY CONTROLLED DRUG RELEASEen_US
dc.typeDissertationen_US
dc.contributor.publisherDigital Repository at the University of Marylanden_US
dc.contributor.publisherUniversity of Maryland (College Park, Md.)en_US
dc.contributor.departmentBioengineeringen_US
dc.subject.pqcontrolledNanoscienceen_US
dc.subject.pqcontrolledNanotechnologyen_US
dc.subject.pquncontrolledControlled releaseen_US
dc.subject.pquncontrolledDoxorubicinen_US
dc.subject.pquncontrolledDrug Deliveryen_US
dc.subject.pquncontrolledNanoparticleen_US
dc.subject.pquncontrolledQuantum Dotsen_US
dc.subject.pquncontrolledTargeted deliveryen_US


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