title: Increased uptake of liposomal-DNA complexes by lung metastases following intravenous administration.
abstract: 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.
authors.affiliation: Department of Thoracic and Cardiovascular Surgery, 77030, Houston, Texas, USA
authors.forename: Isao
authors.initials: I
authors.lastname: Ito
authors.forename: Gopalan
authors.initials: G
authors.lastname: Began
authors.forename: Imran
authors.initials: I
authors.lastname: Mohiuddin
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Saeki
authors.forename: Yuji
authors.initials: Y
authors.lastname: Saito
authors.forename: Cynthia D
authors.initials: CD
authors.lastname: Branch
authors.forename: Ara
authors.initials: A
authors.lastname: Vaporciyan
authors.forename: L Clifton
authors.initials: LC
authors.lastname: Stephens
authors.forename: Nancy
authors.initials: N
authors.lastname: Yen
authors.forename: Jack A
authors.initials: JA
authors.lastname: Roth
authors.forename: Rajagopal
authors.initials: R
authors.lastname: Ramesh
mesh_terms: D000818:Animals; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism* / Q000556:secondary / Q000628:therapy; D002470:Cell Survival; D002784:Cholesterol / Q000378:metabolism*; D004247:DNA / Q000378:metabolism*; D005229:Fatty Acids, Monounsaturated / Q000378:metabolism*; D015316:Genetic Therapy; D006801:Humans; D007124:Immunoenzyme Techniques; D007275:Injections, Intravenous; D008081:Liposomes; D008156:Luciferases / Q000378:metabolism; D008175:Lung Neoplasms / Q000378:metabolism* / Q000556:secondary / Q000628:therapy; D051379:Mice; D008809:Mice, Inbred C3H; D010587:Phagocytosis; D010873:Pinocytosis; D000644:Quaternary Ammonium Compounds / Q000378:metabolism*; D019076:Transgenes; D014407:Tumor Cells, Cultured
chemical_list: D005229:Fatty Acids, Monounsaturated; D008081:Liposomes; D000644:Quaternary Ammonium Compounds; D004247:DNA; D002784:Cholesterol; D008156:Luciferases; C070046:1,2-dioleoyloxy-3-(trimethylammonium)propane