Superparamagnetic iron oxide nanoparticles-loaded chitosan-linoleic acid nanoparticles as an effective hepatocyte-targeted gene delivery system.
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 (99m)Tc-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.
Department of Nuclear Medicine, Chonbuk National University Medical School and Hospital, Jeonju, Republic of Korea.
Su-Jin
SJ
Cheong
Chang-Moon
CM
Lee
Se-Lim
SL
Kim
Hwan-Jeong
HJ
Jeong
Eun-Mi
EM
Kim
Eun-Hye
EH
Park
Dong Wook
DW
Kim
Seok Tae
ST
Lim
Myung-Hee
MH
Sohn
D000818:Animals; D002478:Cells, Cultured; D048271:Chitosan / Q000008:administration & dosage*; D005260:Female; D005290:Ferric Compounds / Q000008:administration & dosage*; D018390:Gene Targeting / Q000379:methods; D018014:Gene Transfer Techniques; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D019787:Linoleic Acid / Q000008:administration & dosage*; D008280:Magnetics; D051379:Mice; D008807:Mice, Inbred BALB C; D053758:Nanoparticles / Q000008:administration & dosage*
D005290:Ferric Compounds; C000499:ferric oxide; D048271:Chitosan; D019787:Linoleic Acid