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

Research Paper

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

Mulan Li^1,3,†, Hoe Suk Kim^1,2,†, Lianji Tian^1,3, Mi Kyung Yu⁴, Sangyong Jon⁴, Woo Kyung Moon^{1,2,3 ✉}

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.

✉ Corresponding author: WK Moon, Department of Radiology, Seoul National University Hospital, 101 Daehangno, Jongno-gu, Seoul 110-744, Republic of Korea. Tel: 82-2-2072-3928, E-mail: moonwkac.kr

Abstract

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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