Date of Award
Summer 8-2020
Document Type
Thesis
Degree Name
Master of Science (MS)
Department
Pharmaceutical Sciences
First Advisor
Dr. Hamidreza Montazeri
Second Advisor
Dr. Keykavous Parang
Third Advisor
Dr. Tiwari Rakesh
Fourth Advisor
Dr. Innokentiy Maslennikov
Abstract
Delivering siRNA is challenging due to many obstacles, such as extremely short in vivo half-life, rapid elimination via glomerular filtration, and inability to cross cell membranes due to the hydrophilic and negatively-charged nature. Thus, a delivery system is needed to deliver the siRNA into the cells by crossing the negatively-charged phospholipid cell membrane. The goal of this project was to design hybrid cyclic-linear peptides as siRNA delivery system. We designed and synthesized hybrid cyclic-linear peptides [R5K]W5, [R6K]W6, and [R5K]W7 containing positively-charged arginine residues attached to hydrophobic tryptophan chains for more efficient interaction with siRNA and to improve siRNA internalization into the cell. SYBR Green II dye exclusion assay showed a high binding affinity of the peptides with siRNA. The delivery of siRNA into the cells was further enhanced by incorporating hybrid peptides into a multi-component structure called Peptide/Lipid-Associated Nucleic Acids (PLANAs). The efficiency of PLANA for delivery of siRNA to human breast cancer cells was studied by using flow cytometry, exhibiting significantly higher uptake of siRNA with PLANA-containing peptides. The PLANA containing siRNA exhibited protein silencing more efficiently than that of lipofectamine.
Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.
Recommended Citation
Alasmari, A. Hybrid Cyclic/Linear Peptides in a Multi-Component Lipid Structure as a siRNA Delivery System. [master’s thesis]. Irvine, CA: Chapman University; https://doi.org/10.36837/chapman.000194