PEG-Functionalized Magnetic Nanoparticles for Drug Delivery and Magnetic Resonance Imaging Applications
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Polyethylene glycol (PEG) functionalized magnetic nanoparticles (MNPs) were tested as a drug carrier system, as a magnetic resonance imaging (MRI) agent, and for their ability to conjugate to an antibody.
An iron oxide core coated with oleic acid (OA) and then with OA-PEG forms a water-dispersible MNP formulation. Hydrophobic doxorubicin partitions into the OA layer for sustained drug delivery. The T1 and T2 MRI contrast properties were determined in vitro and the circulation of the MNPs was measured in mouse carotid arteries. An N-hydroxysuccinimide group (NHS) on the OA-PEG-80 was used to conjugate the amine functional group on antibodies for active targeting in the human MCF-7 breast cancer cell line.
The optimized formulation had a mean hydrodynamic diameter of 184 nm with an ~8 nm iron-oxide core. The MNPs enhance the T2 MRI contrast and have a long circulation time in vivo with 30% relative concentration 50 min post-injection. Doxorubicin-loaded MNPs showed sustained drug release and dose-dependent antiproliferative effects in vitro; the drug effect was enhanced with transferrin antibody-conjugated MNPs.
PEG-functionalized MNPs could be developed as a targeted drug delivery system and MRI contrast agent.
KEY WORDSanticancer drugs anti-proliferative effect contrast agent iron-oxide reticuloendothelial system transferrin antibody
The study reported here is funded by grant R01 EB005822 (to VL) from the National Institute of Biomedical Imaging and Bioengineering of the National Institutes of Health. SPF is a predoctoral student in Cleveland Clinic’s Molecular Medicine Ph.D. Program, which is funded by the “Med into Grad” initiative of the Howard Hughes Medical Institute (http://www.lerner.ccf.org/molecmed/phd/).
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