Doxorubicin-Conjugated Heparin-Coated Superparamagnetic Iron Oxide Nanoparticles for Combined Anticancer Drug Delivery and Magnetic Resonance Imaging

In this study, superparamagnetic iron oxide (SPIO) nanoparticles (NPs) with an average size of 10 +/- 2 nm were coated with doxorubicin (Dox)-conjugated heparin (DH-SPIO) and were used for targeted anticancer drug delivery, and as a magnetic resonance imaging (MRI) contrast agent. The DH-SPIO NPs had a mean particle size of 125 +/- 10 nm and a zeta potential of -35 +/- 3 mV. Fourier transform-infrared spectroscopy, X-ray diffraction spectroscopy, transmission electron microscopy, vibrating sample magnetometry, and MTT assay were used to investigate the properties of DH-SPIO NPs. The internalization of DH-SPIO NPs into A549 tumor cells was examined using fluorescence microscopy and quantified by flow cytometry. Prussian blue staining, total iron assay, in vitro MRI and transmission electron microscopy showed that DH-SPIO NPs had high superparamagnetic clustering effect. In vivo therapy of A549 human lung carcinoma, DH-SPIO NPs displayed a higher efficacy than Dox in inhibiting tumor growth and prolonging the survival of mice bearing tumors. Meanwhile, the pathological damage to the cardiac tissue in mice treated with DH-SPIO NPs was significantly less severe than that of mice treated with free Dox at the same dosage. These results show that DH-SPIO NPs are promising biomaterials for combined drug therapy and clinical imaging.