Original Paper

JBIC Journal of Biological Inorganic Chemistry

, 14:253

First online:

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

  • Ting-Jung ChenAffiliated withDepartment of Biological Science and Technology, National Chiao Tung University
  • , Tsan-Hwang ChengAffiliated withDepartment of Biological Science and Technology, Chung Hwa University of Medical Technology
  • , Chiao-Yun ChenAffiliated withDepartment of Medical Imaging, Kaohsiung Medical University HospitalDepartment of Radiology, Kaohsiung Medical University
  • , Sodio C. N. HsuAffiliated withFaculty of Medicinal and Applied Chemistry, Kaohsiung Medical University
  • , Tian-Lu ChengAffiliated withFaculty of Biomedical Science and Environmental Biology, Kaohsiung Medical University
  • , Gin-Chung LiuAffiliated withDepartment of Medical Imaging, Kaohsiung Medical University HospitalDepartment of Radiology, Kaohsiung Medical University
  • , Yun-Ming WangAffiliated withDepartment of Biological Science and Technology, National Chiao Tung UniversityFaculty of Medicinal and Applied Chemistry, Kaohsiung Medical University Email author 

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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.

Keywords

Superparamagnetic iron oxide Herceptin HER2/neu receptor Magnetic resonance imaging