Synthesis and characterization of chemically condensed oligoethylenimine containing beta-aminopropionamide linkages for siRNA delivery

Biomaterials. 2007 Sep;28(25):3731-40. doi: 10.1016/j.biomaterials.2007.04.037. Epub 2007 May 3.

Abstract

Polyethylenimines (PEI) are often inefficient in gene knockdown experiments with small interfering RNA (siRNA), presumably due to the strong complexing properties. A more efficient and potentially degradable oligoethylenimine-based carrier was synthesized by the condensation of 800 molecular weight PEI oligomers with hexanedioldiacrylate. Reaction conditions were chosen such that Michael reaction occurs followed by complete N-acylation of all residual ester bonds resulting in beta-aminopropionamide linkage sites and an average molecular weight of 30,000. Based on NMR analysis, these conditions produced 38% tertiary amides and 62% secondary amides, with about 2% residual carboxylate, presumably from hydrolysis. The ionizable equivalent weight of the carrier increased to 51, compared to a value of 43 for standard PEI. Sensible in vitro knockdown of the luciferase gene in stably transfected HUH7 cells, up to 80% in comparison to non-specific siRNA, demonstrated its suitability for siRNA delivery.

MeSH terms

  • Amides / chemical synthesis
  • Amides / chemistry
  • Biocompatible Materials / chemical synthesis*
  • Biocompatible Materials / chemistry
  • Cell Line, Tumor
  • Humans
  • Luciferases / genetics
  • Luciferases / metabolism
  • Magnetic Resonance Spectroscopy
  • Molecular Structure
  • Particle Size
  • Polyethyleneimine / chemical synthesis*
  • Polyethyleneimine / chemistry
  • RNA, Small Interfering / genetics*
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Spectrophotometry, Infrared
  • Transfection / methods*

Substances

  • Amides
  • Biocompatible Materials
  • RNA, Small Interfering
  • Recombinant Fusion Proteins
  • Polyethyleneimine
  • Luciferases