Folate-targeted, cationic liposome-mediated gene transfer into disseminated peritoneal tumors

Gene Ther. 2002 Nov;9(22):1542-50. doi: 10.1038/


A folate-targeted, cationic lipid based transfection complex was developed and found to specifically transfect folate receptor-expressing cells and tumors. These liposomal vectors were comprised of protamine-condensed plasmid DNA, a mixture of cationic and neutral lipids, and a folic acid-cysteine-polyethyleneglycol-phosphatidylethanolamine (FA-Cys-PEG-PE) conjugate. Pre-optimization studies revealed that inclusion of low amounts (0.01 to 0.03%) of FA-Cys-PEG-PE yielded the highest binding activity of dioleoylphosphatidylcholine/cholesterol liposomes to folate receptor-bearing cells. In contrast, higher amounts (>0.5%) of FA-Cys-PEG-PE progressively decreased cellular binding of the liposomes. In vitro studies with cationic lipid/dioleoylphosphatidylethanolamine formulations indicated that as little as 0.01 to 0.3% of FA-Cys-PEG-PE was needed to produce optimal targeted expression of plasmid DNA. Similarly, using a disseminated intraperitoneal L1210A tumor model, maximum in vivo transfection activity occurred with intraperitoneally administered formulations that contained low amounts (0.01 mol%) of the FA-Cys-PEG-PE targeting lipid. Overall, folate-labeled formulations produced an eight- to 10-fold increase in tumor-associated luciferase expression, as compared with the corresponding non-targeted cationic lipid/DNA formulations. These results collectively indicate that transfection of widespread intraperitoneal cancers can be significantly enhanced using folate-targeted techniques.

MeSH terms

  • Animals
  • Carrier Proteins / metabolism*
  • Cell Line
  • Female
  • Folate Receptors, GPI-Anchored
  • Folic Acid / genetics*
  • Folic Acid / metabolism
  • Gene Targeting / methods*
  • Genetic Therapy / methods*
  • Liposomes
  • Luciferases / genetics
  • Mice
  • Mice, Inbred DBA
  • Peritoneal Neoplasms / metabolism
  • Peritoneal Neoplasms / therapy*
  • Protein Binding
  • Receptors, Cell Surface*
  • Transfection / methods


  • Carrier Proteins
  • Folate Receptors, GPI-Anchored
  • Liposomes
  • Receptors, Cell Surface
  • Folic Acid
  • Luciferases