| dc.identifier.uri | http://hdl.handle.net/11401/76322 | |
| 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 | Thesis | |
| dcterms.abstract | Chemotherapy is one of the most commonly used cancer treatments. However, many side effects could occur due to the non-specific bindings of extremely toxic anti-cancer drugs to healthy cells and organs. Targeted delivery has been developed to enhance the selectivity of drug delivery vehicle and minimize side effects of chemotherapy. In this study, the hydrophobically modified glycol chitosan (HGC) micelle was further modified with a biotin-avidin-biotin (B-A-B) strategy to improve the tumor-selective ability of HGC. Firstly, HGC was biotinylated either at the amine groups (NH2) or the hydroxyl groups (OH) on the chitosan main chain. Then the biotin-4-fluorescein, as a model biomolecule, was linked to biotinylated HGC via the strong and specific biotin-avidin linkage. A near-infrared fluorescent dye cyanine 5.5 was also conjugated to the amine groups on HGC for the additional visualization of HGC micelles. The hydrodynamic diameters of these two types of nanoparticles were 197.9±6.4 nm (NH2-conjugated) and 173.6±3.8 nm (OH-conjugated), and their surface charges were 20.3±2.1 mV (NH2-conjugated) and 12.0±1.2 mV (OH-conjugated), ensuring the enhanced permeability and retention (EPR) effect of nanoparticles and their interactions with negatively charged cancer cells membranes. Both types of nanoparticles were delivered at a concentration of 0.3 mg/mL to the 4T1 mouse breast cancer cells. Confocal microscope images showed that nanoparticles were distributed evenly throughout the cytoplasm of cancer cells after 6 hours of exposure. Co-localization of the Cy5.5 and FITC signals further confirmed the formation of BHGC-A-B4F structure. | |
| dcterms.abstract | Chemotherapy is one of the most commonly used cancer treatments. However, many side effects could occur due to the non-specific bindings of extremely toxic anti-cancer drugs to healthy cells and organs. Targeted delivery has been developed to enhance the selectivity of drug delivery vehicle and minimize side effects of chemotherapy. In this study, the hydrophobically modified glycol chitosan (HGC) micelle was further modified with a biotin-avidin-biotin (B-A-B) strategy to improve the tumor-selective ability of HGC. Firstly, HGC was biotinylated either at the amine groups (NH2) or the hydroxyl groups (OH) on the chitosan main chain. Then the biotin-4-fluorescein, as a model biomolecule, was linked to biotinylated HGC via the strong and specific biotin-avidin linkage. A near-infrared fluorescent dye cyanine 5.5 was also conjugated to the amine groups on HGC for the additional visualization of HGC micelles. The hydrodynamic diameters of these two types of nanoparticles were 197.9±6.4 nm (NH2-conjugated) and 173.6±3.8 nm (OH-conjugated), and their surface charges were 20.3±2.1 mV (NH2-conjugated) and 12.0±1.2 mV (OH-conjugated), ensuring the enhanced permeability and retention (EPR) effect of nanoparticles and their interactions with negatively charged cancer cells membranes. Both types of nanoparticles were delivered at a concentration of 0.3 mg/mL to the 4T1 mouse breast cancer cells. Confocal microscope images showed that nanoparticles were distributed evenly throughout the cytoplasm of cancer cells after 6 hours of exposure. Co-localization of the Cy5.5 and FITC signals further confirmed the formation of BHGC-A-B4F structure. | |
| dcterms.available | 2017-09-20T16:50:01Z | |
| dcterms.contributor | Cao, Jian | en_US |
| dcterms.contributor | Meng, Yizhi | en_US |
| dcterms.contributor | Gersappe, Dilip. | en_US |
| dcterms.creator | Li, Weiyi | |
| dcterms.dateAccepted | 2017-09-20T16:50:01Z | |
| dcterms.dateSubmitted | 2017-09-20T16:50:01Z | |
| dcterms.description | Department of Materials Science and Engineering. | en_US |
| dcterms.extent | 82 pg. | en_US |
| dcterms.format | Monograph | |
| dcterms.format | Application/PDF | en_US |
| dcterms.identifier | http://hdl.handle.net/11401/76322 | |
| dcterms.issued | 2015-12-01 | |
| dcterms.language | en_US | |
| dcterms.provenance | Made available in DSpace on 2017-09-20T16:50:01Z (GMT). No. of bitstreams: 1
Li_grad.sunysb_0771M_12492.pdf: 3032458 bytes, checksum: feb6a9d6ef5fc83aa365b439e55bb230 (MD5)
Previous issue date: 1 | en |
| dcterms.publisher | The Graduate School, Stony Brook University: Stony Brook, NY. | |
| dcterms.subject | Avidin, Biotin, Biotinylation, Chitosan, Micelle, Targeted delivery | |
| dcterms.subject | Materials Science | |
| dcterms.title | Biotinylated self-assembled micelles as potential vehicles for targeted anti-cancer drug delivery | |
| dcterms.type | Thesis | |
