Theranostics 2012; 2(1):76-85. doi:10.7150/thno.3462

Research Paper

Comparison of Two Ultrasmall Superparamagnetic Iron Oxides on Cytotoxicity and MR Imaging of Tumors

Mulan Li1,3,†, Hoe Suk Kim1,2,†, Lianji Tian1,3, Mi Kyung Yu4, Sangyong Jon4, Woo Kyung Moon1,2,3 ✉

1. Department of Radiology, Seoul National University Hospital, 101 Daehangno, Jongno-gu, Seoul 110-744, Korea
2. The Institute of Radiation Medicine, Medical Research Center, Seoul National University, 101 Daehangno, Jongno-gu, Seoul 110-744, Korea
3. Department of Biomedical Science, College of Medicine, Seoul National University, Seoul, 101 Daehangno, Jongno-gu, Seoul 110-744, Korea
4. Cell Dynamics Research Center, School of Life Sciences, Gwangju Institute of Science and Technology, 261 Chemdangwagi-ro, Gwangju 500-712, Korea
These authors contributed equally to this work.


Purpose: This study was performed to compare the cytotoxicity and magnetic resonance (MR) contrast in diverse cultured cells and xenograft tumors models of two ultra-small superparamagnetic iron oxides (USPIOs), thermally cross-linked superparamagnetic iron oxide nanoparticles (TCL-SPION) and monocrystalline iron oxide nanoparticles (MION-47).

Materials and methods: Transmission electron microscopy (TEM) images and R2 relaxivity values of the TCL-SPION and MION-47 were obtained and the cell viability and cell growth velocity of treated and untreated human fibroblasts and human umbilical vein endothelial cells (HUVEC) were evaluated. The effect of TCL-SPION and MION-47 on the secretion of interlukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α), the production of nitric oxides and the mitochondrial membrane potentials in murine macrophage cells (RAW264.7) was compared. Human hepatocellular carcinoma cells (HepG2, 5x105) were subcutaneously injected into nude mice (BALB/c) and in vivo MR imaging of tumors before and after injection with TCL-SPION or MION-47 (12.5 mg Fe/kg) was performed on a 1.5 Tesla MRI scanner.

Results: On TEM images, the average core diameter of TCL-SPION was 9 nm whereas that of MION-47 was 5 nm. TCL- SPION (345.0 ± 6.2 mM-1sec-1) had higher relaxivity (R2) than MION-47 (130.7 ± 1.1 mM-1sec-1). Significant changes in cell viability and growth were not found in human fibroblasts and HUVEC exposed to TCL-SPION and MION-47. However, IL-6 and TNF-α secretions increased dose-dependently and significantly in the macrophages treated with MION-47 or TCL-SPION. TCL-SPION had a lower stimulatory effect on IL-6 secretions than did MION-47 (P <0.05) and nitric oxides were produced in the macrophages by MION-47 but not TCL-SPION. A change in the mitochondrial membrane potential of the macrophages was observed 24 hours after the exposure, and MION-47 induced more collapses of the mitochondrial membrane potential than did TCL-SPION. In the in vivo MR imaging, 33.0 ± 1.3% and 7.5 ± 0.4% signal intensity decrease on T2*-weighted images was observed in the tumors injected with TCL-SPION and MION-47, respectively.

Conclusion: Due to the modified surface properties and larger core size of its iron oxide nanoparticles, TCL-SPION achieves lower cytotoxicity and better tumor MR contrast than MION-47. Our study suggests that TCL-SPION may be used as a new platform for tumor imaging and therapy monitoring.

Keywords: Ultra-small superparamagnetic iron oxides, Magnetic resonance imaging, TCL-SPION, MION-47, Tumor targeting.

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How to cite this article:
Li M, Kim HS, Tian L, Yu MK, Jon S, Moon WK. Comparison of Two Ultrasmall Superparamagnetic Iron Oxides on Cytotoxicity and MR Imaging of Tumors. Theranostics 2012; 2(1):76-85. doi:10.7150/thno.3462. Available from