Doxorubicin-modified magnetic nanoparticles as a drug delivery system for magnetic resonance imaging-monitoring magnet-enhancing tumor chemotherapy
Journal
International Journal of Nanomedicine
Journal Volume
11
Pages
2021-2037
Date Issued
2016
Author(s)
Abstract
In this study, we developed functionalized superparamagnetic iron oxide (SPIO) nanoparticles consisting of a magnetic Fe3 O4 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. ? 2016 Liang et al.
SDGs
Other Subjects
doxorubicin; macrogol; superparamagnetic iron oxide nanoparticle; antineoplastic agent; doxorubicin; iron; macrogol derivative; magnetite nanoparticle; silane derivative; animal experiment; animal model; animal tissue; apoptosis; Article; cardiotoxicity; colon carcinoma; controlled study; DNA cross linking; drug absorption; drug accumulation; drug delivery system; drug formulation; drug half life; female; HT 29 cell line; human; human cell; hysteresis; in vitro study; in vivo study; liver toxicity; magnetic field; male; nonhuman; nuclear magnetic resonance imaging; particle size; rat; transmission electron microscopy; tumor volume; animal; Bagg albino mouse; cell proliferation; chemistry; drug delivery system; drug effects; endocytosis; HT-29 cell line; infrared spectroscopy; magnetism; metabolism; Neoplasms; nude mouse; pathology; procedures; proton nuclear magnetic resonance; Sprague Dawley rat; synthesis; temperature; X ray diffraction; Animals; Antineoplastic Agents; Cell Proliferation; Doxorubicin; Drug Delivery Systems; Endocytosis; HT29 Cells; Humans; Iron; Magnetic Resonance Imaging; Magnetics; Magnetite Nanoparticles; Male; Mice, Inbred BALB C; Mice, Nude; Neoplasms; Particle Size; Polyethylene Glycols; Proton Magnetic Resonance Spectroscopy; Rats, Sprague-Dawley; Silanes; Spectroscopy, Fourier Transform Infrared; Temperature; X-Ray Diffraction
Type
journal article