Cell-specific targeting polymeric gene delivery carriers

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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
Date Created 2012-04-24
Date Modified 2012-04-24
ID 190778
Reference URL https://collections.lib.utah.edu/ark:/87278/s6rv0qfg