Journal
INTERNATIONAL JOURNAL OF PHARMACEUTICS
Volume 372, Issue 1-2, Pages 169-176Publisher
ELSEVIER
DOI: 10.1016/j.ijpharm.2009.01.009
Keywords
Gene delivery; Superparamagnetic iron oxide; nanoparticles; Chitosan; Linoleic acid; Hepatocyte; Molecular imaging
Categories
Funding
- National R&D Program for Cancer Control, Ministry for Health, Welfare and Family affairs, Republic of Korea [0620220, 0720420]
- Korea Science and Engineering Foundation
- Ministry of Science Technology [M20702000003-08N0200-00310]
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The goal of this study was to develop a gene delivery imaging system that targets hepatocytes to help diagnose and treat various liver diseases. To this end, we prepared superparamagnetic iron oxide nanoparticles (SPIO)-loaded with water-soluble chitosan (WSC)-linoleic acid (LA) nanoparticles (SCLNs) that formed gene complexes capable of localizing specifically to hepatocytes. We confirmed that Tc-99m-labeled SCLNs delivered into mice via intravenous injection accumulated mainly in the liver using nuclear and magnetic resonance imaging. SCLN/enhanced green fluorescence protein (pEGFP) complexes were also successfully formed and were characterized with a gel retardation assay. SCLN/pEGFP complexes were transfected into primary hepatocytes, where GFP expression was observed in the cytoplasm. In addition, the injection of the gene complexes into mice resulted in significantly increased expression of GFP in hepatocytes in vivo. Furthermore, gene silencing was effectively achieved by administration of gene complexes loaded with specific siRNAs. In conclusion, our results indicate that the SCLNs have the potential to be useful for hepatocyte-targeted imaging and effective gene delivery into hepatocytes. (c) 2009 Elsevier B.V. All rights reserved.
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