Acta Pharmacologica Sinica 2007 December; 28 (12): 2019-2026; doi: 10.1111/j.1745-7254.2007.00661.x

Original Article
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Specific targeting of gliomas with multifunctional superparamagnetic iron oxide nanoparticle optical and magnetic resonance imaging contrast agents1

Xiang-xi MENG2, Jia-qi WAN4, Meng JING2, Shi-guang ZHAO2, Wei CAI3, En-zhong LIU2,4

2Department of Neurosurgery, First Affiliated Hospital, Harbin Medical University, Harbin 150001, China; 3School of Material Science and Engineering, Harbin Institute of Technology, Harbin 150001, China


Aim: To determine whether glioma cells can be specifically and efficiently targeted by superparamagnetic iron oxide nanoparticle (SPIO)-fluorescein isothiocyanate (FITC)-chlorotoxin (SPIOFC) that is detectable by magnetic resonance imaging (MRI) and optical imaging.


Methods: SPIOFC was synthesized by conjugating SPIO with FITC and chlorotoxin. Glioma cells (human U251-MG and rat C6) were cultured with SPIOFC and SPIOF (SPIO-FITC), respectively. Neural cells were treated with SPIOFC as the control for SPIOFC-targeted glioma cells. The internalization of SPIOFC by glioma cells was assessed by MRI and was quantified using inductively-coupled plasma emission spectroscopy. The optical imaging ability of SPIOFC was evaluated by confocal laser scanning microscopy.


Results: Iron per cell of U251 (72.5±1.8 pg) and C6 (74.9±2.2 pg) cells cultured with SPIOFC were significantly more than those of U251 (6.6±1.0 pg) and C6 (7.1±0.8 pg) cells incubated with SPIOF. The T2 signal intensity of U251 and C6 cells cultured with SPIOFC (233.6±25.9 and 211.4±17.2, respectively) were substantially lower than those of U251 and C6 cells incubated with SPIOF (2275.3±268.6 and 2342.7±222.4, respectively). Moreover, there were significant differences in iron per cell and T2 signal intensity between SPIOFC-treated neural cells (1.3±0.3; 2533.6±199.2) and SPIOFC-treated glioma cells. SPIOFC internalized by glioma cells exhibited green fluorescence by confocal laser scanning microscopy.

SPIOFC is suitable for the specific and efficient targeting of glioma cells. MRI and optical imaging in conjunction with SPIOFC can differentiate glioma cells from normal brain tissue cells.


Keywords: superparamagnetic iron oxide; nanoparticles; gliomas; biocompatibility; magnetic resonance imaging; optical imaging; molecular imaging

1 Project supported by the National Natural Science Foundation of China (No 30672154 and No 30371458) and the Science and Technology Research Project of the Department of Education of Heilongjiang Province (No 11511191).

4 Correspondence to Prof En-zhong LIU.
Phn 86-451-8426-0286.
Fax 86-451-5363-3660.
Received 2006-12-04     Accepted 2007-05-16

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