Efficacy of MRI visible iron oxide nanoparticles in delivering minicircle DNA into liver via intrabiliary infusion.

Abstract

Gene therapy is a very promising technology for treatment of liver diseases. Minicircle DNA (MCDNA) is a versatile gene vector, which possesses excellent features in bio-safety and duration of transgene expression. However, its application has been hampered by the lack of an efficient gene delivery system. In this study, we developed a magnetic resonance imaging (MRI) visible nanoparticle to monitor MCDNA gene delivery and explore the potential of gene therapy in vivo. The nanoparticle was constructed via self-assembly of stearic acid modified low molecular polyethyleneimine (stPEI) and superparamagnetic iron oxide (SPIO) nanocrystals. The multiple SPIO nanocrystals with a controlled clustering structure in the nanoparticles were designed to achieve high MRI sensitivity. Furthermore, the MCDNA was combined with the nanoparticles via electronic interaction. Through intrabiliary infusion, the stPEI-SPIO/MCDNA nanoparticles were efficiently delivered to liver that was visualized by MRI in vivo and confirmed by histology. Moreover, the MCDNA nanoparticles exhibited non-cytotoxicity with no obvious inflammation in the transfection sites. These results indicate that stPEI-SPIO nanoparticle is able to serve as both an efficient DNA vector delivery system and a sensitive agent for MRI visualization.