Increased uptake of liposomal-DNA complexes by lung metastases following intravenous administration

Mol Ther. 2003 Mar;7(3):409-18. doi: 10.1016/s1525-0016(03)00004-2.


We have investigated the effects of an improved liposomal formulation (extruded DOTAP:cholesterol (DOTAP:Chol)-DNA complex) on transgene expression in tumor cells and normal cells of murine and human origin both in vitro and in vivo. In vitro, transgene expression was significantly increased (P = 0.01) in human tumor cells compared to normal human cells. The increased transgene expression was due to increased uptake of the liposome-DNA complex by tumor cell phagocytosis. Furthermore, immunohistochemical analysis demonstrated a greater transgene expression in lung tumors than in surrounding normal tissues. Increased transgene expression due to enhanced uptake of the liposome-DNA complexes by tumor cells in vivo was also demonstrated using fluorescently labeled DOTAP:Chol liposomes. Finally, evaluation of lung tissue explants obtained from patients undergoing pulmonary resection demonstrated significantly higher (P = 0.001) transgene expression in tumor cells than in normal cells. Thus, we demonstrated that intravenous injection of DOTAP:Chol-DNA complex results in increased transgene expression in tumor and is due to increased phagocytosis of the complexes by tumor cells.

Publication types

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

MeSH terms

  • Animals
  • Carcinoma, Non-Small-Cell Lung / metabolism*
  • Carcinoma, Non-Small-Cell Lung / secondary
  • Carcinoma, Non-Small-Cell Lung / therapy
  • Cell Survival
  • Cholesterol / metabolism*
  • DNA / metabolism*
  • Fatty Acids, Monounsaturated / metabolism*
  • Genetic Therapy
  • Humans
  • Immunoenzyme Techniques
  • Injections, Intravenous
  • Liposomes
  • Luciferases / metabolism
  • Lung Neoplasms / metabolism*
  • Lung Neoplasms / secondary
  • Lung Neoplasms / therapy
  • Mice
  • Mice, Inbred C3H
  • Phagocytosis
  • Pinocytosis
  • Quaternary Ammonium Compounds / metabolism*
  • Transgenes
  • Tumor Cells, Cultured


  • Fatty Acids, Monounsaturated
  • Liposomes
  • Quaternary Ammonium Compounds
  • DNA
  • Cholesterol
  • Luciferases
  • 1,2-dioleoyloxy-3-(trimethylammonium)propane