title: Efficient suppression of murine intracellular adhesion molecule-1 using ultrasound-responsive and mannose-modified lipoplexes inhibits acute hepatic inflammation.
abstract: Hepatitis is often associated with the overexpression of various adhesion molecules. In particular, intracellular adhesion molecule-1 (ICAM-1), which is expressed on hepatic endothelial cells (HECs) in the early stage of inflammation, is involved in serious illnesses. Therefore, ICAM-1 suppression in HECs enables the suppression of inflammatory responses. Here, we developed an ICAM-1 small interfering RNA (siRNA) transfer method using ultrasound (US)-responsive and mannose-modified liposome/ICAM-1 siRNA complexes (Man-PEG(2000) bubble lipoplexes [Man-PEG(2000) BLs]), and achieved efficient HEC-selective ICAM-1 siRNA delivery in combination with US exposure. Moreover, the sufficient ICAM-1 suppression effects were obtained via this ICAM-1 siRNA transfer in vitro and in vivo, and potent anti-inflammatory effects were observed in various types of inflammation, such as lipopolysaccharide, dimethylnitrosamine, carbon tetrachloride, and ischemia/reperfusion-induced inflammatory mouse models.
  
  
  CONCLUSIONS
  HEC-selective and efficient ICAM-1 siRNA delivery using Man-PEG(2000) BLs and US exposure enables suppression of various types of acute hepatic inflammation. This novel siRNA delivery method may offer a valuable system for medical treatment where the targeted cells are HECs.
authors.affiliation: Department of Drug Delivery Research, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto, Japan.
authors.forename: Keita
authors.initials: K
authors.lastname: Un
authors.forename: Shigeru
authors.initials: S
authors.lastname: Kawakami
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Yoshida
authors.forename: Yuriko
authors.initials: Y
authors.lastname: Higuchi
authors.forename: Ryo
authors.initials: R
authors.lastname: Suzuki
authors.forename: Kazuo
authors.initials: K
authors.lastname: Maruyama
authors.forename: Fumiyoshi
authors.initials: F
authors.lastname: Yamashita
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Hashida
mesh_terms: D000208:Acute Disease; D000704:Analysis of Variance; D000818:Animals; D002478:Cells, Cultured; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism; D015316:Genetic Therapy / Q000379:methods*; D006505:Hepatitis / Q000473:pathology / Q000628:therapy*; D022781:Hepatocytes / Q000166:cytology / Q000378:metabolism; D066298:In Vitro Techniques; D018799:Intercellular Adhesion Molecule-1 / Q000187:drug effects* / Q000235:genetics*; D008081:Liposomes / Q000737:chemistry / Q000494:pharmacology; D008297:Male; D008358:Mannose / Q000737:chemistry / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D034741:RNA, Small Interfering / Q000235:genetics / Q000494:pharmacology*; D011897:Random Allocation; D012016:Reference Values; D014162:Transfection / Q000379:methods; D014464:Ultrasonic Therapy / Q000379:methods*
chemical_list: D008081:Liposomes; D034741:RNA, Small Interfering; D018799:Intercellular Adhesion Molecule-1; D008358:Mannose