Improved siRNA delivery efficiency via solvent-induced condensation of micellar nanoparticles

Juan Wu, Wei Qu, John Michael Williford, Yong Ren, Xuesong Jiang, Xuan Jiang, Deng Pan, Hai Quan Mao*, Erik Luijten

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

Efficient delivery of short interfering RNA (siRNA) remains one of the primary challenges of RNA interference therapy. Polyethylene glycol (PEG)ylated polycationic carriers have been widely used for the condensation of DNA and RNA molecules into complex-core micelles. The PEG corona of such nanoparticles can significantly improve their colloidal stability in serum, but PEGylation of the carriers also reduces their condensation capacity, hindering the generation of micellar particles with sufficient complex stability. This presents a particularly significant challenge for packaging siRNA into complex micelles, as it has a much smaller size and more rigid chain structure than DNA plasmids. Here, we report a new method to enhance the condensation of siRNA with PEGylated linear polyethylenimine using organic solvent and to prepare smaller siRNA nanoparticles with a more extended PEG corona and consequently higher stability. As a proof of principle, we have demonstrated the improved gene knockdown efficiency resulting from the reduced siRNA micelle size in mice livers following intravenous administration.

Original languageEnglish (US)
Article number204002
JournalNanotechnology
Volume28
Issue number20
DOIs
StatePublished - Apr 25 2017

Keywords

  • gene therapy
  • nanoparticle
  • siRNA delivery
  • size control
  • solvent polarity

ASJC Scopus subject areas

  • Bioengineering
  • Chemistry(all)
  • Materials Science(all)
  • Mechanics of Materials
  • Mechanical Engineering
  • Electrical and Electronic Engineering

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