Doxorubicin-modified magnetic nanoparticles as a drug delivery system for magnetic resonance imaging-monitoring magnet-enhancing tumor chemotherapy.
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 (r 2) for SPIO-PEG-D was significantly higher than the longitudinal relaxivity (r 1) (r 2/r 1 >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.
Institute of Biomedical Engineering, College of Medicine, College of Engineering, National Taiwan University Hospital, Taipei, Taiwan; Department of Medical Imaging, National Taiwan University Hospital, Taipei, Taiwan.
Po-Chin
PC
Liang
Institute of Biomedical Engineering, College of Medicine, College of Engineering, National Taiwan University Hospital, Taipei, Taiwan; Biomedical Technology and Device Research Labs, Industrial Technology Research Institute, Hsinchu, Taiwan.
Yung-Chu
YC
Chen
Institute of Biomedical Engineering, College of Medicine, College of Engineering, National Taiwan University Hospital, Taipei, Taiwan.
Chi-Feng
CF
Chiang
Division of Gastroenterology, Department of Internal Medicine, E-Da Hospital, Kaohsiung, Taiwan.
Lein-Ray
LR
Mo
Department of Medical Imaging, National Taiwan University Hospital, Taipei, Taiwan.
Shwu-Yuan
SY
Wei
Biomedical Technology and Device Research Labs, Industrial Technology Research Institute, Hsinchu, Taiwan.
Wen-Yuan
WY
Hsieh
Institute of Biomedical Engineering, College of Medicine, College of Engineering, National Taiwan University Hospital, Taipei, Taiwan; Institute of Biomedical Engineering and Nanomedicine, National Health Research Institutes, Miaoli, Taiwan.
Win-Li
WL
Lin
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D049109:Cell Proliferation / Q000187:drug effects; D004317:Doxorubicin / Q000494:pharmacology / Q000627:therapeutic use*; D016503:Drug Delivery Systems / Q000379:methods*; D004705:Endocytosis / Q000187:drug effects; D019073:HT29 Cells; D006801:Humans; D007501:Iron / Q000378:metabolism; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008280:Magnetics / Q000379:methods*; D058185:Magnetite Nanoparticles / Q000737:chemistry*; D008297:Male; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D010316:Particle Size; D011092:Polyethylene Glycols / Q000138:chemical synthesis / Q000737:chemistry; D066244:Proton Magnetic Resonance Spectroscopy; D017207:Rats, Sprague-Dawley; D012821:Silanes / Q000138:chemical synthesis / Q000737:chemistry; D017550:Spectroscopy, Fourier Transform Infrared; D013696:Temperature; D014961:X-Ray Diffraction
D000970:Antineoplastic Agents; D058185:Magnetite Nanoparticles; D012821:Silanes; D011092:Polyethylene Glycols; D004317:Doxorubicin; D007501:Iron
MRI monitoring; chemotherapy; doxorubicin; magnet enhancing; polyethylene glycol; superparamagnetic iron oxide