Precisely tunable engineering of sub-30 nm monodisperse oligonucleotide nanoparticles

J Am Chem Soc. 2014 Jan 8;136(1):234-40. doi: 10.1021/ja408879b. Epub 2013 Dec 17.


Advancement of RNAi therapies is mainly hindered by the development of efficient delivery vehicles. The ability to create small size (<30 nm) oligonucleotide nanoparticles is essential for many aspects of the delivery process but is often overlooked. In this report, we describe diblock star polymers that can reproducibly complex double-stranded oligonucleotides into monodisperse nanoparticles with 15, 23, or 30 nm in diameter. The polymer-nucleic acid nanoparticles have a core-shell architecture with dense PEG brush coating. We characterized these nanoparticles using ITC, DLS, FRET, FCS, TIRF, and TEM. In addition to small size, these nanoparticles have neutral zeta-potentials, making the presented polymer architecture a very attractive platform for investigation of yet poorly studied polyplex size range for siRNA and antisense oligonucleotide delivery applications.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Bioengineering
  • Calorimetry
  • Cell Survival
  • HeLa Cells
  • Humans
  • Microscopy, Electron, Transmission
  • Molecular Structure
  • Nanoparticles / chemistry*
  • Oligonucleotides / chemistry*
  • Particle Size
  • Polyethylene Glycols / chemistry*


  • Oligonucleotides
  • Polyethylene Glycols