title: siRNA delivery to lung-metastasized tumor by systemic injection with cationic liposomes.
abstract: BACKGROUND
  Cationic liposomes can efficiently deliver siRNA to the lung by intravenous injection of cationic liposome/siRNA complexes (lipoplexes).
  
  
  OBJECTIVE
  The aim of this study was to examine a formulation of cationic liposomes for siRNA delivery to lung metastasis of breast tumor.
  
  
  METHODS
  For the preparation of cationic liposomes, 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP) or dimethyldioctadecylammonium bromide (DDAB) as a cationic lipid and cholesterol (Chol) or 1,2-dioleoyl-L-α-glycero-3-phosphatidylethanolamine (DOPE) as a neutral lipid were used. In vitro and in vivo gene silencing effects by cationic lipoplexes were evaluated after transfection into stably luciferase-expressing human breast tumor MCF-7-Luc cells and after intravenous injection into mice with lung MCF-7-Luc metastasis, respectively. Intracellular localization of siRNA after transfection into MCF-7 cells by cationic lipoplexes and biodistribution of siRNA after intravenous injection of cationic lipoplexes into the mice with lung metastasis were examined by confocal and fluorescent microscopy analyses, respectively.
  
  
  RESULTS
  In in vitro transfection, DOTAP/DOPE and DDAB/DOPE lipoplexes of luciferase siRNA strongly suppressed luciferase activity in MCF-7-Luc cells, but DOTAP/Chol and DDAB/Chol lipoplexes did not, although DOTAP/Chol and DDAB/Chol lipoplexes exhibited higher cellular uptake than DOTAP/DOPE and DDAB/DOPE lipoplexes. When their cationic lipoplexes were intravenously injected into mice with lung MCF-7-Luc metastasis, siRNAs were mainly accumulated in the lungs; however, the reduced luciferase activities in the lung-metastasized tumors were observed only by injections of DOTAP/Chol and DOTAP/DOPE lipoplexes, but not by DDAB/Chol and DDAB/DOPE lipoplexes.
  
  
  CONCLUSIONS
  DOTAP-based liposomes might be useful as an in vivo siRNA delivery carrier that can induce gene silencing in lung-metastasized tumors.
authors.affiliation: a Institute of Medicinal Chemistry, Hoshi University , Shinagawa-ku , Tokyo , Japan.
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Hattori
authors.affiliation: a Institute of Medicinal Chemistry, Hoshi University , Shinagawa-ku , Tokyo , Japan.
authors.forename: Ayako
authors.initials: A
authors.lastname: Nakamura
authors.affiliation: a Institute of Medicinal Chemistry, Hoshi University , Shinagawa-ku , Tokyo , Japan.
authors.forename: Shohei
authors.initials: S
authors.lastname: Arai
authors.affiliation: a Institute of Medicinal Chemistry, Hoshi University , Shinagawa-ku , Tokyo , Japan.
authors.forename: Kumi
authors.initials: K
authors.lastname: Kawano
authors.affiliation: a Institute of Medicinal Chemistry, Hoshi University , Shinagawa-ku , Tokyo , Japan.
authors.forename: Yoshie
authors.initials: Y
authors.lastname: Maitani
authors.affiliation: a Institute of Medicinal Chemistry, Hoshi University , Shinagawa-ku , Tokyo , Japan.
authors.forename: Etsuo
authors.initials: E
authors.lastname: Yonemochi
mesh_terms: D000818:Animals; D002412:Cations / Q000008:administration & dosage / Q000737:chemistry; D004337:Drug Carriers / Q000008:administration & dosage* / Q000737:chemistry* / Q000493:pharmacokinetics; D005260:Female; D020868:Gene Silencing; D006801:Humans; D007275:Injections, Intravenous; D008081:Liposomes; D008175:Lung Neoplasms / Q000378:metabolism* / Q000556:secondary*; D061986:MCF-7 Cells; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D010316:Particle Size; D034741:RNA, Small Interfering / Q000008:administration & dosage* / Q000235:genetics / Q000493:pharmacokinetics*; D013499:Surface Properties; D014018:Tissue Distribution; D014407:Tumor Cells, Cultured
chemical_list: D002412:Cations; D004337:Drug Carriers; D008081:Liposomes; D034741:RNA, Small Interfering
keywords: Breast tumor; cationic liposome; gene knockdown; lung metastasis; siRNA delivery