Dicetyl phosphate-tetraethylenepentamine-based liposomes for systemic siRNA delivery

Bioconjug Chem. 2011 Mar 16;22(3):429-35. doi: 10.1021/bc1004697. Epub 2011 Mar 1.


Dicetyl phosphate-tetraethylenepentamine (DCP-TEPA) conjugate was newly synthesized and formed into liposomes for efficient siRNA delivery. Formulation of DCP-TEPA-based polycation liposomes (TEPA-PCL) complexed with siRNA was examined by performing knockdown experiments using stable EGFP-transfected HT1080 human fibrosarcoma cells and siRNA for GFP. An adequate amount of DCP-TEPA in TEPA-PCL and N/P ratio of TEPA-PCL/siRNA complexes were determined based on the knockdown efficiency. Then, the biodistribution of TEPA-PCL modified with poly(ethylene glycol) (PEG) was examined in BALB/c mice. As a result, TEPA-PCL modified with PEG6000 avoided reticuloendothelial system uptake and showed long circulation in the bloodstream. On the other hand, PEGylation of TEPA-PCL/siRNA complexes caused dissociation of a portion of the siRNA from the liposomes. However, we found that the use of cholesterol-conjugated siRNA improved the interaction between TEPA-PCL and siRNA, which allowed PEGylation of TEPA-PCL/siRNA complexes without siRNA dissociation. In addition, TEPA-PCL complexed with cholesterol-conjugated siRNA showed potent knockdown efficiency in stable luciferase-transfected B16-F10 murine melanoma cells. Finally, the biodistribution of cholesterol-conjugated siRNA formulated in PEGylated TEPA-PCL was examined by performing near-infrared fluorescence imaging in Colon26 NL-17 murine carcinoma-bearing mice. Our results showed that tumor targeting with siRNA via systemic administration was achieved by using PEGylated TEPA-PCL combined with active targeting with Ala-Pro-Arg-Pro-Gly, a peptide used for targeting angiogenic endothelium.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • Cell Line, Tumor
  • Cholesterol / metabolism
  • Ethylenediamines / chemistry*
  • Fibrosarcoma / metabolism
  • Fibrosarcoma / pathology
  • Gene Silencing
  • Humans
  • Injections, Intravenous
  • Liposomes / administration & dosage
  • Liposomes / chemical synthesis
  • Liposomes / chemistry*
  • Liposomes / pharmacokinetics
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Molecular Imaging
  • Organophosphates / chemistry*
  • Polyethylene Glycols / chemistry
  • RNA, Small Interfering / genetics
  • RNA, Small Interfering / metabolism*
  • Spectrophotometry, Infrared


  • Ethylenediamines
  • Liposomes
  • Organophosphates
  • RNA, Small Interfering
  • dicetylphosphate
  • Polyethylene Glycols
  • Cholesterol
  • tetraethylenepentamine