| Publication Type |
dissertation |
| School or College |
College of Pharmacy |
| Department |
Pharmaceutics & Pharmaceutical Chemistry |
| Author |
Suh, Won-Hee |
| Title |
Cell-specific targeting polymeric gene delivery carriers |
| Date |
2001-08 |
| Description |
Cell-specific polymeric gene delivery carriers targeted to leukemia T cells and angiogenic endothelial cells, were designed and developed using anti-JL1 antibody and alpha-v-beta3/alpha-v-beta5 integrin-binding RCD-4C peptide as targeting moieties. In the first part of this thesis, an angiogenic endothelial cell-targeting polymeric gene carrier was synthesized by conjugating RGD-4C peptide with the cationic polymer polyethyleneimine (PEI) using a heterobifunctional polyethylene glycol (PEG) linker. The incorporation of hydrophilic PEG into PEI improved poor physicochemical properties of DNA/PEI complexes; however, the extensive grafting of PEI with PEG was shown to inhibit DNA condensation process, significantly decreasing transfection efficiency. In in vitro transfection experiments, PEI-g-1PEG-RGD showed high specificity to angiogenic endothelial cells, compared to normal endothelial cells. Also PEI-g-1PEG-RGD exhibited approximately a five-fold increase in transfection with angiogenic endothelial cells over PEI homopolymer, probably due to an integrin-mediated internalization pathway. In the second part of this thesis, a leukemia-specific polymeric gene delivery carrier was developed by carbohydrate site-directed modification of anti-JL1 antibody with the cationic polymer, polylysine (PLL). The composition and antigen binding affinity of anti-JL1 antibody-PLL conjugates were analyzed by amino acid analysis and flow cytometry respectively. In the experiments with Molt 4 (human leukemia T cells), anti-JL1 antibody-PLL/DNA complexes were efficiently internalized into the cytoplasm after a 4 hour incubation at 37°C and showed significantly higher in vitro transfection efficiency than PLL/DNA complexes and DNA/Lipofectin formulation. This high efficiency of anti-JL1 antibody-containing PLL might result from the targeting effect of receptor-mediated endocytosis induced by anti-JL1 antibody. |
| Type |
Text |
| Publisher |
University of Utah |
| Subject |
Drug Delivery Systems; Polymeric Drugs |
| Subject MESH |
Gene Targeting; Gene Therapy; Leukemia |
| Dissertation Institution |
University of Utah |
| Dissertation Name |
PhD |
| Language |
eng |
| Relation is Version of |
Digital reproduction of "Cell-specific targeting polymeric gene delivery carriers." Spencer S. Eccles Health Sciences Library. Print version of "Cell-specific targeting polymeric gene delivery carriers." available at J. Willard Marriott Library Special Collection. RS43.5 2001 .S84. |
| Rights Management |
© Won-Hee Suh. |
| Format Medium |
application/pdf |
| Format Extent |
2,565,728 bytes |
| Identifier |
undthes,5221 |
| Source |
Original: University of Utah Spencer S. Eccles Health Sciences Library (no longer available). |
| Funding/Fellowship |
Expression Genetics Inc. |
| Master File Extent |
2,565,767 bytes |
| ARK |
ark:/87278/s6rv0qfg |
| Setname |
ir_etd |
| ID |
190778 |
| Reference URL |
https://collections.lib.utah.edu/ark:/87278/s6rv0qfg |
