Journal
JOURNAL OF CONTROLLED RELEASE
Volume 169, Issue 3, Pages 228-238Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.jconrel.2013.02.015
Keywords
Superparamagnetic iron-oxide (SPIO) nanocomposites; pH-sensitive; Controlled release; PEGylation; Magnetic resonance imaging (MRI); Theranostics
Funding
- National Basic Research Program [2012CB821500, 2013CB834506]
- Shanghai Rising-Star Program [11QH1401500]
- China National Funds for Distinguished Young Scientists [21025417]
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A multifunctional pH-sensitive superparamagnetic iron-oxide (SPIO) nanocomposite system was developed for simultaneous tumor magnetic resonance imaging (MRI) and therapy. Small-size SPIO nanoparticles were chemically bonded with antitumor drug doxorubicin (DOX) and biocompatible poly(ethylene glycol) (PEG) through pH-sensitive acylhydrazone linkages, resulting in the formation of SPIO nanocomposites with magnetic targeting and pH-sensitive properties. These DOX-conjugated SPIO nanocomposites exhibited not only good stability in aqueous solution but also high saturation magnetizations. Under an acidic environment, the DOX was quickly released from the SPIO nanocomposites due to the cleavage of pH-sensitive acylhydrazone linkages. With the help of magnetic field, the DOX-conjugated SPIO nanocomposites showed high cellular uptake, indicating their magnetic targeting property. Comparing to free DOX, the DOX-conjugated SPIO nanocomposites showed better antitumor effect under magnetic field. At the same time, the relaxivity value of these SPIO nanocomposites was higher than 146 s(-1) mM(-1) Fe, leading to similar to 4 times enhancement compared to that of free SPIO nanoparticles. As a negative contrast agent, these SPIO nanocomposites illustrated high resolution in MRI diagnosis of tumor-bearing mice. All of these results confirm that these pH-sensitive SPIO nanocomposites are promising hybrid materials for synergistic MRI diagnosis and tumor therapy. (C) 2013 Elsevier B. V. All rights reserved.
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