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Permanent link (DOI): https://doi.org/10.7939/R3BD4M

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Lipid Modified Polymers for Transfection of Human CRL Fibroblasts, and for siRNA Mediated MDR Reversal in Melanoma Cancer Therapy Open Access

Descriptions

Other title
Subject/Keyword
Chemotherapy
Fibroblast
Plasmid DNA
Transfection
SCID Mice
Multidrug Resistance
Polymer
siRNA
Non Viral Gene Delivery
Doxorubicin
Tumor
Paclitaxel
In Vivo Gene Delivery
P-glycoprotein
Melanoma Cancer
Type of item
Thesis
Degree grantor
University of Alberta
Author or creator
Abbasi Dezfouli, Meysam
Supervisor and department
Uludag, Hasan (Chemical & Materials Engineering)
Examining committee member and department
Weinfeld, Michael (Oncology)
Pun, Suzie (Bioengineering)
Willman, Alan (Biomedical Engineering)
Hugh, Judith (Laboratory Medicine & Pathology)
Berthiaume, Luc (Cell Biology)
Burrell, Robert (Biomedical Engineering)
Department
Department of Biomedical Engineering
Specialization

Date accepted
2010-08-31T16:57:19Z
Graduation date
2010-11
Degree
Doctor of Philosophy
Degree level
Doctoral
Abstract
Gene delivery for therapeutic purposes is quickly emerging as the best potential treatment option for inherited genetic diseases and cancer. Viral gene carriers have been the choice for this purpose due to their high efficiency, but harmful immunogenic and oncogenic host reactions have limited their in vivo use. Cationic polymers provide a safe alternative to viral carriers as they can be engineered to reduce immunogenic and toxic responses and serve therapeutic purposes in the body. Due to their strong positive charge, they are able to compact the negatively charged nucleotides to small nano-sized particles appropriate for cellular uptake. Additionally, they efficiently encapsulate the highly sensitive nucleotides, and protect them against degradation by the nucleases present at the physiological milieu. In this thesis work, I have used a novel approach for gene delivery by combining the critical properties of a cationic polymer (i.e., nucleotide condensing ability) with that of a fatty acid (i.e., lipid membrane compatibility). The resulting lipid modified polymer increased delivery of our gene of interest into target cells and resulted in increased siRNA delivery for cancer gene therapy.
Language
English
DOI
doi:10.7939/R3BD4M
Rights
Permission is hereby granted to the University of Alberta Libraries to reproduce single copies of this thesis and to lend or sell such copies for private, scholarly or scientific research purposes only. Where the thesis is converted to, or otherwise made available in digital form, the University of Alberta will advise potential users of the thesis of these terms. The author reserves all other publication and other rights in association with the copyright in the thesis and, except as herein before provided, neither the thesis nor any substantial portion thereof may be printed or otherwise reproduced in any material form whatsoever without the author's prior written permission.
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