International Journal of Nanomedicine (May 2016)
Doxorubicin-modified magnetic nanoparticles as a drug delivery system for magnetic resonance imaging-monitoring magnet-enhancing tumor chemotherapy
Abstract
Po-Chin Liang,1,2,* Yung-Chu Chen,1,3,* Chi-Feng Chiang,1 Lein-Ray Mo,4 Shwu-Yuan Wei,2 Wen-Yuan Hsieh,3 Win-Li Lin1,5 1Institute of Biomedical Engineering, College of Medicine, College of Engineering, 2Department of Medical Imaging, National Taiwan University Hospital, Taipei, 3Biomedical Technology and Device Research Labs, Industrial Technology Research Institute, Hsinchu, 4Division of Gastroenterology, Department of Internal Medicine, E-Da Hospital, Kaohsiung, 5Institute of Biomedical Engineering and Nanomedicine, National Health Research Institutes, Miaoli, Taiwan *These authors contributed equally in this work Abstract: In this study, we developed functionalized superparamagnetic iron oxide (SPIO) nanoparticles consisting of a magnetic Fe3O4 core and a shell of aqueous stable polyethylene glycol (PEG) conjugated with doxorubicin (Dox) (SPIO-PEG-D) for tumor magnetic resonance imaging (MRI) enhancement and chemotherapy. The size of SPIO nanoparticles was ~10 nm, which was visualized by transmission electron microscope. The hysteresis curve, generated with vibrating-sample magnetometer, showed that SPIO-PEG-D was superparamagnetic with an insignificant hysteresis. The transverse relaxivity (r2) for SPIO-PEG-D was significantly higher than the longitudinal relaxivity (r1) (r2/r1 >10). The half-life of Dox in blood circulation was prolonged by conjugating Dox on the surface of SPIO with PEG to reduce its degradation. The in vitro experiment showed that SPIO-PEG-D could cause DNA crosslink more serious, resulting in a lower DNA expression and a higher cell apoptosis for HT-29 cancer cells. The Prussian blue staining study showed that the tumors treated with SPIO-PEG-D under a magnetic field had a much higher intratumoral iron density than the tumors treated with SPIO-PEG-D alone. The in vivo MRI study showed that the T2-weighted signal enhancement was stronger for the group under a magnetic field, indicating that it had a better accumulation of SPIO-PEG-D in tumor tissues. In the anticancer efficiency study for SPIO-PEG-D, the results showed that there was a significantly smaller tumor size for the group with a magnetic field than the group without. The in vivo experiments also showed that this drug delivery system combined with a local magnetic field could reduce the side effects of cardiotoxicity and hepatotoxicity. The results showed that the developed SPIO-PEG-D nanoparticles own a great potential for MRI-monitoring magnet-enhancing tumor chemotherapy. Keywords: superparamagnetic iron oxide, polyethylene glycol, doxorubicin, MRI monitoring, magnet enhancing, chemotherapy
