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GRAPHENE NANORIBBONS ELICIT CELL SPECIFIC UPTAKE AND DRUG DELIVERY VIA ACTIVATION OF EPIDERMAL GROWTH FACTOR RECEPTORS

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dc.contributor.advisor Sitharaman, Balaji en_US
dc.contributor.author Mullick Chowdhury, Sayan en_US
dc.contributor.other Department of Molecular and Cellular Biology. en_US
dc.date.accessioned 2017-09-20T16:50:25Z
dc.date.available 2017-09-20T16:50:25Z
dc.date.issued 2014-12-01 en_US
dc.identifier.uri http://hdl.handle.net/11401/76495 en_US
dc.description 237 pg. en_US
dc.description.abstract Ligands such as peptides, antibodies or other epitopes bind and activate specific cell receptors, and can be employed for targeted cellular delivery of pharmaceuticals such as drugs, genes and imaging agents. In this dissertation, I investigate the in vitro and hematological compatibility of oxidized graphene nanoribbons, non-covalently functionalized with PEG-DSPE (1, 2-distearoyl-sn-glycero-3-phosphoethanolamine-N[amino(polyethyleneglycol)]) (O-GNR-PEG-DSPE) and evaluate its potential as a drug delivery agent. Although, O-GNR-PEG-DSPE was found to interact with RBC membrane and induce structural changes in them, they did not affect other hematological parameters. In vitro studies showed that these particles activate epidermal growth factor receptors (EGFRs) and elicit cell specific uptake and concentration dependent toxicity in cells over-expressing these receptors. Receptor activation was found to occur through a mechanism involving membrane depolarization and influx of extracellular Ca2+. This activation generates a dynamin-dependent macropinocytosis-like response, and results in significant O-GNR-PEG-DSPE uptake into cells with high EGFR expression. Cells with an integrated human papillomavirus (HPV) genome also show increased uptake due to the modulation of the activated EFGR by the viral protein E5. I demonstrate that this cell specific uptake of O-GNR-PEG-DSPE can be exploited to achieve significantly enhanced drug efficacies even in drug resistant cells and xenograft tumors. These results have implications towards the development of active targeting and delivery agents without ligand functionalization for use in the diagnosis and treatment of pathologies that over-express EGFR or mediated by HPV. en_US
dc.description.sponsorship This work is sponsored by the Stony Brook University Graduate School in compliance with the requirements for completion of degree. en_US
dc.format Monograph en_US
dc.format.medium Electronic Resource en_US
dc.language.iso en_US en_US
dc.publisher The Graduate School, Stony Brook University: Stony Brook, NY. en_US
dc.subject.lcsh Biomedical engineering en_US
dc.subject.other Chemotherapy, Drug delivery, EGFR, Graphene, HPV, Targeted delivery en_US
dc.title GRAPHENE NANORIBBONS ELICIT CELL SPECIFIC UPTAKE AND DRUG DELIVERY VIA ACTIVATION OF EPIDERMAL GROWTH FACTOR RECEPTORS en_US
dc.type Dissertation en_US
dc.mimetype Application/PDF en_US
dc.contributor.committeemember Shroyer, Kenneth en_US
dc.contributor.committeemember Clark, Richard en_US
dc.contributor.committeemember Hearing, Patrick en_US
dc.contributor.committeemember McElroy, Anne. en_US


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