Polymer nanocarrier system for endosome escape and timed release of siRNA with complete gene silencing and cell death in cancer cells

Gu, Wenyi, Jia, Zhongfan, Truong, Nghia P., Prasadam, Indira, Xiao, Yin, & Monteiro, Michael J. (2013) Polymer nanocarrier system for endosome escape and timed release of siRNA with complete gene silencing and cell death in cancer cells. Biomacromolecules, 14(10), pp. 3386-3389.

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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.

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23 citations in Web of Science®

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ID Code: 62400
Item Type: Journal Article
Refereed: Yes
Keywords: Polymer Nanoparticles, Timed release, Osteosarcoma, PLK1 siRNA, Drug delivery
DOI: 10.1021/bm401139e
ISSN: 1525-7797
Subjects: Australian and New Zealand Standard Research Classification > BIOLOGICAL SCIENCES (060000)
Australian and New Zealand Standard Research Classification > ENGINEERING (090000) > BIOMEDICAL ENGINEERING (090300) > Biomaterials (090301)
Divisions: Current > Schools > School of Chemistry, Physics & Mechanical Engineering
Current > Institutes > Institute of Health and Biomedical Innovation
Current > QUT Faculties and Divisions > Science & Engineering Faculty
Deposited On: 12 Nov 2013 23:19
Last Modified: 13 Nov 2013 21:01

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