Efficient intracellular delivery of oligonucleotides formulated in folate receptor-targeted lipid vesicles

Bioconjug Chem. Nov-Dec 2002;13(6):1220-5. doi: 10.1021/bc025569z.


In this study, a novel lipid vector has been developed for targeted delivery of oligodeoxynucleotides (ODN) to tumors that overexpress folate receptor. This is based on a method developed by Semple et al. (1), which utilizes an ionizable aminolipid (1,2-dioleoyl-3-(dimethylammonio)propane, DODAP) and an ethanol-containing buffer system for encapsulating large quantities of polyanionic ODN in lipid vesicles. Folate is incorporated into the lipid vesicles via a distearoylphosphatidylethanolamine-poly(ethylene glycol) (DSPE-PEG) spacer. These vesicles are around 100-200 nm in diameter with an ODN entrapment efficiency of 60-80%. Folate mediated efficient delivery of ODN to KB cells that overexpress folate receptor. Uptake of folate-targeted lipidic ODN by KB cells is about 8-10-fold more efficient than that of lipidic ODN without a ligand or free ODN. This formulation is resistant to serum. Thus, targeted delivery of ODN via this novel lipid vector may have potential in treating tumors that overexpress folate receptors.

Publication types

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

MeSH terms

  • Base Sequence
  • Biological Transport / drug effects
  • Carrier Proteins / metabolism*
  • Ceramides
  • Drug Carriers / metabolism*
  • Drug Delivery Systems*
  • Folate Receptors, GPI-Anchored
  • Folic Acid / metabolism*
  • Humans
  • Intracellular Fluid / metabolism*
  • KB Cells
  • Liposomes / metabolism*
  • Microscopy, Fluorescence
  • Oligodeoxyribonucleotides / genetics
  • Oligodeoxyribonucleotides / metabolism*
  • Polyethylene Glycols
  • Receptors, Cell Surface*


  • Carrier Proteins
  • Ceramides
  • Drug Carriers
  • Folate Receptors, GPI-Anchored
  • Liposomes
  • Oligodeoxyribonucleotides
  • Receptors, Cell Surface
  • Polyethylene Glycols
  • Folic Acid