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Efficient suppression of murine intracellular adhesion molecule‐1 using ultrasound‐responsive and mannose‐modified lipoplexes inhibits acute hepatic inflammation
Author(s) -
Un Keita,
Kawakami Shigeru,
Yoshida Mitsuru,
Higuchi Yuriko,
Suzuki Ryo,
Maruyama Kazuo,
Yamashita Fumiyoshi,
Hashida Mitsuru
Publication year - 2012
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.25607
Subject(s) - inflammation , small interfering rna , intercellular adhesion molecule 1 , lipopolysaccharide , in vivo , icam 1 , in vitro , cell adhesion molecule , mannose receptor , intracellular , liposome , transfection , chemistry , immunology , cancer research , medicine , biology , biochemistry , macrophage , gene , microbiology and biotechnology
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. Conclusion : 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. (H EPATOLOGY 2012;56:259–269)