Efficient suppression of murine intracellular adhesion molecule-1 using ultrasound-responsive and mannose-modified lipoplexes inhibits acute hepatic inflammation.

Abstract

UNLABELLED:

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.

• Authors: Keita Un, Shigeru Kawakami, Mitsuru Yoshida, Yuriko Higuchi, Ryo Suzuki, Kazuo Maruyama, Fumiyoshi Yamashita, Mitsuru Hashida
• Journal: Hepatology (Baltimore, Md.) (Hepatology) Vol. 56 Issue 1 Pg. 259-69 (Jul 2012) ISSN: 1527-3350 [Electronic] United States
• PMID: 22271390 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 American Association for the Study of Liver Diseases.

Chemical References

• Liposomes
• RNA, Small Interfering
• Intercellular Adhesion Molecule-1
• Mannose

Topics

• Acute Disease
• Analysis of Variance
• Animals
• Cells, Cultured
• Disease Models, Animal
• Endothelial Cells (cytology, metabolism)
• Genetic Therapy (methods)
• Hepatitis (pathology, therapy)
• Hepatocytes (cytology, metabolism)
• In Vitro Techniques
• Intercellular Adhesion Molecule-1 (drug effects, genetics)
• Liposomes (chemistry, pharmacology)
• Male
• Mannose (chemistry, pharmacology)
• Mice
• Mice, Inbred C57BL
• RNA, Small Interfering (genetics, pharmacology)
• Random Allocation
• Reference Values
• Transfection (methods)
• Ultrasonic Therapy (methods)