Journal of Biological Inorganic Chemistry 2009-02-01

Targeted Herceptin-dextran iron oxide nanoparticles for noninvasive imaging of HER2/neu receptors using MRI.

Ting-Jung Chen, Tsan-Hwang Cheng, Chiao-Yun Chen, Sodio C N Hsu, Tian-Lu Cheng, Gin-Chung Liu, Yun-Ming Wang

Index: J. Biol. Inorg. Chem. 14(2) , 253-60, (2009)

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Abstract

A novel magnetic resonance imaging (MRI) contrast agent containing Herceptin is reported. The surfaces of superparamagnetic iron oxide nanoparticles were modified with dextran and conjugated with Herceptin (Herceptin-nanoparticles) to improve their dispersion, magnetization, and targeting of the specific receptors on cells. From analytical results, we found that Herceptin-nanoparticles were well dispersed in solutions of various pH range, and had no hysteresis, high saturation magnetization (80 emu/g), and low cytotoxicity to a variety of cells. Notably, the magnetic resonance enhancements for the different breast cancer cell lines (BT-474, SKBR-3, MDA-MB-231, and MCF-7) are proportional to the HER2/neu expression level in vitro. When Herceptin-nanoparticles were administered to mice bearing breast tumor allograft by intravenous injection, the tumor site was detected in T (2)-weighted magnetic resonance images as a 45% enhancement drop, indicating a high level of accumulation of the contrast agent within the tumor sites. Therefore, targeting of cancer cells was observed by in vitro and in vivo MRI studies using Herceptin-nanoparticles contrast agent. In addition, Herceptin-nanoparticles enhancing the magnetic resonance signal intensity were sufficient to detect the cell lines with a low level of HER2/neu expression.