| dc.identifier.uri | http://hdl.handle.net/11401/77168 | |
| 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 | Amphiphilic block copolymers with both a hydrophobic domain and a hydrophilic domain can thermodynamically self-assemble into ordered structures such as spherical micelles, worm-like micelles or vesicles in selective solvents which have great potential for biomedical applications such as drug/gene delivery. Stimuli-responsive amphiphilic block copolymers which can change morphology in response to internal or external stimulus have great potential to achieve controlled release of drugs or genes at specific sites. In this dissertation, two types of stimuli-responsive star-shaped triblock copolymers PEO-S(CKn)-PLA and PEO-(PDEAm)-PLA were synthesized and studied. Amphiphilic cationic star-shaped triblock copolymers with poly(ethylene oxide), poly(D,L-lactide), and poly(L-lysine arms) (PEO-S(CKn)-PLA) were synthesized by a combination of ring opening polymerization (ROP) and arm coupling through a thiol-disulfide exchange reaction. The morphology of PEO-S(Boc)-PLA diblock copolymers, PEO-S(CKn)-PLA triblock copolymers, and PEO-S(CKn)-PLA /GFP DNA complexes were characterized by dynamic light scattering (DLS) and small-angle X-ray scattering (SAXS). PEO-S(CKn)-PLA could effectively condense DNA into nanosized complexes suitable for endocytotic cellular uptake and retard GFP DNA migration in agarose gel electrophoresis at N/P ratios (ratio of moles of the primary amine groups of cationic polymers to those of the phosphate groups of DNA) ) greater than 1. In vitro gene transfection studies in the HeLa cell line showed that the amphiphilic structure could enhance gene transfection when compared to the corresponding polylysine. Addition of chloroquine could further enhance the gene transfection efficiency by interfering with the endocytosis process to enhance endosomal escape of the complexes. The cytotoxicity of PEO-S(CKn)-PLA triblock copolymers was studied in HeLa cells by MTS assay. PEO2k-S(CK40)-PLA2k triblock copolymers showed almost no toxicity at all conditions examined while the corresponding polylysine PLL40 and branched PEI showed relatively low toxicity at low concentrations but high toxicity at high concentrations. | |
| dcterms.available | 2017-09-20T16:52:08Z | |
| dcterms.contributor | Bhatia, Surita | en_US |
| dcterms.contributor | Grubbs, Robert B | en_US |
| dcterms.contributor | Chiu, Melanie | en_US |
| dcterms.contributor | Montclare, Jin. | en_US |
| dcterms.creator | WU, TIANYUAN | |
| dcterms.dateAccepted | 2017-09-20T16:52:08Z | |
| dcterms.dateSubmitted | 2017-09-20T16:52:08Z | |
| dcterms.description | Department of Chemistry. | en_US |
| dcterms.extent | 145 pg. | en_US |
| dcterms.format | Application/PDF | en_US |
| dcterms.format | Monograph | |
| dcterms.identifier | http://hdl.handle.net/11401/77168 | |
| dcterms.issued | 2015-12-01 | |
| dcterms.language | en_US | |
| dcterms.provenance | Made available in DSpace on 2017-09-20T16:52:08Z (GMT). No. of bitstreams: 1
WU_grad.sunysb_0771E_12661.pdf: 3887126 bytes, checksum: f041da579124ab798059474cbd2160c8 (MD5)
Previous issue date: 1 | en |
| dcterms.publisher | The Graduate School, Stony Brook University: Stony Brook, NY. | |
| dcterms.subject | Gene delivery, Polymer, Stimulus-responsive | |
| dcterms.subject | Chemistry | |
| dcterms.title | Preparation and characterization of stimuli-responsive star-shaped triblock copolymers for gene delivery | |
| dcterms.type | Dissertation | |
