title: Small interfering RNA delivery into the liver by cationic cholesterol derivative-based liposomes.
abstract: OBJECTIVE
  Previously, we reported that the cationic liposomes composed of a cationic cholesterol derivative, cholesteryl (2-((2-hydroxyethyl)amino)ethyl)carbamate (OH-C-Chol) and 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE) (termed LP-C), could deliver small interfering RNAs (siRNAs) with high transfection efficiency into tumor cells. In this study, to develop a liposomal vector for siRNA delivery in vivo, we prepared the poly(ethyleneglycol) (PEG)-modified cationic liposomes (LP-C-PEG) and evaluated their transfection efficiency in vitro and in vivo.
  
  
  METHODS
  We prepared LP-C-PEG/siRNA complexes (LP-C-PEG lipoplexes) formed in water or 50 mM NaCl solution, and evaluated their siRNA biodistribution and gene silencing effect in mice after intravenous injection.
  
  
  RESULTS
  LP-C-PEG lipoplexes strongly exhibited in vitro gene silencing effects in human breast tumor MCF-7 cells as well as LP-C lipoplexes. In particular, formation of LP-C and LP-C-PEG lipoplexes in the NaCl solution increased the cellular association. When LP-C-PEG lipoplexes with Cy5.5-labeled siRNA formed in water or NaCl solution were injected into mice, accumulation of the siRNA was observed in the liver. Furthermore, injection of LP-C-PEG lipoplexes with ApoB siRNA could suppress ApoB mRNA levels in the liver and reduce very-low-density lipoprotein/low-density lipoprotein levels in serum compared with that after Cont siRNA transfection, although the presence of NaCl solution in forming the lipoplexes did not affect gene silencing effects in vivo.
  
  
  CONCLUSIONS
  LP-C-PEG may have potential as a gene vector for siRNA delivery to the liver.
authors.affiliation: a Department of Drug Delivery Research , Hoshi University , Tokyo , Japan and.
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Hattori
authors.affiliation: a Department of Drug Delivery Research , Hoshi University , Tokyo , Japan and.
authors.forename: Yoko
authors.initials: Y
authors.lastname: Machida
authors.affiliation: b Graduate School of Pharmaceutical Sciences, Kyoto University , Kyoto , Japan.
authors.forename: Maho
authors.initials: M
authors.lastname: Honda
authors.affiliation: a Department of Drug Delivery Research , Hoshi University , Tokyo , Japan and.
authors.forename: Nozomi
authors.initials: N
authors.lastname: Takeuchi
authors.affiliation: a Department of Drug Delivery Research , Hoshi University , Tokyo , Japan and.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Yoshiike
authors.affiliation: b Graduate School of Pharmaceutical Sciences, Kyoto University , Kyoto , Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Ohno
authors.affiliation: a Department of Drug Delivery Research , Hoshi University , Tokyo , Japan and.
authors.forename: Hiraku
authors.initials: H
authors.lastname: Onishi
mesh_terms: D000818:Animals; D002412:Cations; D002784:Cholesterol / Q000737:chemistry*; D005260:Female; D020868:Gene Silencing; D018014:Gene Transfer Techniques; D006801:Humans; D008077:Lipoproteins, LDL / Q000737:chemistry / Q000378:metabolism; D008081:Liposomes / Q000008:administration & dosage / Q000737:chemistry* / Q000494:pharmacology; D008099:Liver / Q000187:drug effects*; D061986:MCF-7 Cells; D008807:Mice, Inbred BALB C; D010316:Particle Size; D011092:Polyethylene Glycols / Q000737:chemistry; D034741:RNA, Small Interfering / Q000008:administration & dosage / Q000737:chemistry*; D013499:Surface Properties; D014162:Transfection / Q000379:methods
chemical_list: D002412:Cations; D008077:Lipoproteins, LDL; D008081:Liposomes; D034741:RNA, Small Interfering; D011092:Polyethylene Glycols; D002784:Cholesterol
keywords: Cationic cholesterol derivative; cationic liposome; liver targeting; siRNA delivery; transfection