Please use this identifier to cite or link to this item: https://hdl.handle.net/2440/124902
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Type: Journal article
Title: Polymer nanocarrier system for endosome escape and timed release of siRNA with complete gene silencing and cell death in cancer cells
Author: Gu, W.
Jia, Z.
Truong, N.P.
Prasadam, I.
Xiao, Y.
Monteiro, M.J.
Citation: Biomacromolecules, 2013; 14(10):3386-3389
Publisher: American Chemical Society
Issue Date: 2013
ISSN: 1525-7797
1526-4602
Statement of
Responsibility: 
Wenyi Gu, Zhongfan Jia, Nghia P. Truong, Indira Prasadam, Yin Xiao, and Michael J. Monteiro
Abstract: An influenza virus-inspired polymer mimic nanocarrier was used to deliver siRNA for specific and near complete gene knockdown of an osteoscarcom cell line (U-2SO). The polymer was synthesized by single-electron transfer living radical polymerization (SET-LRP) at room temperature to avoid complexities of transfer to monomer or polymer. It was the only LRP method that allowed good block copolymer formation with a narrow molecular weight distribution. At nitrogen to phosphorus (N/P) ratios of equal to or greater than 20 (greater than a polymer concentration of 13.8 μg/mL) with polo-like kinase 1 (PLK1) siRNA gave specific and near complete (>98%) cell death. The polymer further degrades to a benign polymer that showed no toxicity even at polymer concentrations of 200 μg/mL (or N/P ratio of 300), suggesting that our polymer nanocarrier can be used as a very effective siRNA delivery system and in a multiple dose administration. This work demonstrates that with a well-designed delivery device, siRNA can specifically kill cells without the inclusion of an additional clinically used highly toxic cochemotherapeutic agent. Our work also showed that this excellent delivery is sensitive for the study of off-target knockdown of siRNA.
Keywords: Cell Line, Tumor
Endosomes
Humans
Osteosarcoma
Polymers
RNA, Small Interfering
Drug Carriers
Drug Delivery Systems
Drug Screening Assays, Antitumor
Cell Death
Cell Survival
Gene Silencing
Molecular Structure
Structure-Activity Relationship
Dose-Response Relationship, Drug
Hydrogen-Ion Concentration
Time Factors
Nanoparticles
Rights: © 2013 American Chemical Society
DOI: 10.1021/bm401139e
Grant ID: ARC
Published version: http://dx.doi.org/10.1021/bm401139e
Appears in Collections:Aurora harvest 8
Biochemistry publications

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