| dc.identifier.uri | http://hdl.handle.net/11401/76495 | |
| 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 | |
| dc.format.medium | Electronic Resource | en_US |
| dc.language.iso | en_US | |
| dc.publisher | The Graduate School, Stony Brook University: Stony Brook, NY. | |
| dc.type | Dissertation | |
| dcterms.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. | |
| dcterms.available | 2017-09-20T16:50:25Z | |
| dcterms.contributor | Shroyer, Kenneth | en_US |
| dcterms.contributor | Sitharaman, Balaji | en_US |
| dcterms.contributor | Clark, Richard | en_US |
| dcterms.contributor | Hearing, Patrick | en_US |
| dcterms.contributor | McElroy, Anne. | en_US |
| dcterms.creator | Mullick Chowdhury, Sayan | |
| dcterms.dateAccepted | 2017-09-20T16:50:25Z | |
| dcterms.dateSubmitted | 2017-09-20T16:50:25Z | |
| dcterms.description | Department of Molecular and Cellular Biology. | en_US |
| dcterms.extent | 237 pg. | en_US |
| dcterms.format | Application/PDF | en_US |
| dcterms.format | Monograph | |
| dcterms.identifier | http://hdl.handle.net/11401/76495 | |
| dcterms.issued | 2014-12-01 | |
| dcterms.language | en_US | |
| dcterms.provenance | Made available in DSpace on 2017-09-20T16:50:25Z (GMT). No. of bitstreams: 1
MullickChowdhury_grad.sunysb_0771E_11959.pdf: 8641541 bytes, checksum: 83ec68b8f89c30a93998f5e15cc07a17 (MD5)
Previous issue date: 1 | en |
| dcterms.publisher | The Graduate School, Stony Brook University: Stony Brook, NY. | |
| dcterms.subject | Biomedical engineering | |
| dcterms.subject | Chemotherapy, Drug delivery, EGFR, Graphene, HPV, Targeted delivery | |
| dcterms.title | GRAPHENE NANORIBBONS ELICIT CELL SPECIFIC UPTAKE AND DRUG DELIVERY VIA ACTIVATION OF EPIDERMAL GROWTH FACTOR RECEPTORS | |
| dcterms.type | Dissertation | |
