Polymer Nanocarrier System for Endosome Escape and Timed Release of siRNA with Complete Gene Silencing and Cell Death in Cancer Cells

Wenyi Gu, Zhongfan Jia, Nghia P. Truong, Indira Prasadam, Yin Xiao, Michael J. Monteiro

Research output: Contribution to journalArticle

47 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)3386-3389
Number of pages4
JournalBiomacromolecules
Volume14
Issue number10
DOIs
Publication statusPublished - 14 Oct 2013
Externally publishedYes

Fingerprint Dive into the research topics of 'Polymer Nanocarrier System for Endosome Escape and Timed Release of siRNA with Complete Gene Silencing and Cell Death in Cancer Cells'. Together they form a unique fingerprint.

  • Cite this