Highly Effective T2 MR Contrast Agent Based on Heparinized Superparamagnetic Iron Oxide Nanoparticles

Dong Yun Lee

Macromolecular Research, Vol.19, No.8, 843-847, August, 2011

DOI10.1007/s13233-011-0805-0 Export Citation

Highly Effective T2 MR Contrast Agent Based on Heparinized Superparamagnetic Iron Oxide Nanoparticles

Dong Yun Lee^†

Departments of Bioengineering, College of Engineering, Institute for Bioengineering and Biopharmaceutical Research, Hanyang University, and Hanyang University Institute of Aging Society, Seoul, 133-791, Korea

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In this study a potential magnetic resonance (MR) T2 contrast agent was developed systematically based on heparin-coated superparamagnetic iron oxide (SPIO) nanoparticles. Dextran-coated SPIO, which is commercially available as Feridex®, was prepared for the control group. The size of the crystalline core was adjusted to provide suitable relaxometric properties. Compared to the uncoated SPIO, the heparin or dextran coating provided a better dispersion of SPIO nanoparticles in solution. The zeta potential of the SPIO surface was detected to confirm the polymer coating. The Zeta potential of non-coated SPIO was approximatelt -44 mV, whereas dextran-coated or heparin-coated SPIO was -6.4 and -33.5 mV, respectively. The zeta potential of heparin-coated SPIO was caused by the rich sulfonate group of heparin. In addition, the heparin-coated SPIO showed higher hyponegativity than dextran-coated SPIO. The reason was that the heparin-coated had a lower r2/r1 ratio (18.2) at 1.5-T magnetic resonance imaging (MRI) compared to dextran-coated SPIO (r2/r1 ratio 32.9). Both SPIO nanoparticles can be still suitable for T2-weighted MRI because r2/r1 ratio was >10. From the results of in vitro cellular labeling, heparin-coated SPIO was more advantageous for cellular labeling because it could powerfully visualize the cells after a short incubation time (2 h). From these findings, it is possible that heparin-coated SPIO can be used as a good negative contrast agent in clinical MRI.

Keywords:superparamagnetic iron oxide (SPIO);heparin;relaxivity;MRI;cellular uptake.

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[Referenced By]

[1] Caravan P, Ellison JJ, McMurry TJ, Lauffer RB, Chem. Rev., 99(9), 2293 (1999)

[2] Taler SJ, Textor SC, Canzanello VJ, Schwartz L, Porayko M, Wiesner RH, Krom RA, Transplantation, 62, 1588 (1996)

[3] Ai H, Flask C, Weinberg B, Shuai X, Pagel MD, Farrell D, Duerk J, Gao JM, Adv. Mater., 17(16), 1949 (2005)

[4] Kim J, Lee JE, Lee SH, Yu JH, Lee JH, Park TG, Hyeon T, Adv. Mater., 20(3), 478 (2008)

[5] Ayres RC, Dousset B, Wixon S, Buckels JA, McMaster P, Mayer AD, Lancet, 343, 862 (1994)

[6] Teramura Y, Iwata H, Bioconjugate Chem., 19, 1389 (2008)

[7] Tromsdorf UI, Bruns OT, Salmen SC, Beisiegel U, Weller H, Nano Lett., 9, 4434 (2009)

[8] Kim DK, Mikhaylova M, Zhang Y, Muhammed M, Chem. Mater., 15, 1617 (2003)

[9] Neuberger T, Schopf B, Hofmann H, Hofmann M, Von Rechenberg B, J. Magn. Magn. Mater., 293, 483 (2005)

[10] Arbab AS, Yocum GT, Kalish H, Jordan EK, Anderson SA, Khakoo AY, Read EJ, Frank JA, Blood, 104, 1217 (2004)

[11] Sjogren CE, Johansson C, Naevestad A, Sontum PC, Briley-Saebo K, Fahlvik AK, Magn. Reson. Imaging, 15, 55 (1997)

[12] Josephson L, Tung CH, Moore A, Weissleder R, Bioconjugate Chem., 10, 186 (1999)

[13] Bulte JW, Zhang S, van Gelderen P, Herynek V, Jordan EK, Duncan ID, Frank JA, Proc. Natl. Acad. Sci. U.S.A., 96, 15256 (1999)