JBIC Journal of Biological Inorganic Chemistry

, 14:253

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

Authors

  • Ting-Jung Chen
    • Department of Biological Science and TechnologyNational Chiao Tung University
  • Tsan-Hwang Cheng
    • Department of Biological Science and TechnologyChung Hwa University of Medical Technology
  • Chiao-Yun Chen
    • Department of Medical ImagingKaohsiung Medical University Hospital
    • Department of RadiologyKaohsiung Medical University
  • Sodio C. N. Hsu
    • Faculty of Medicinal and Applied ChemistryKaohsiung Medical University
  • Tian-Lu Cheng
    • Faculty of Biomedical Science and Environmental BiologyKaohsiung Medical University
  • Gin-Chung Liu
    • Department of Medical ImagingKaohsiung Medical University Hospital
    • Department of RadiologyKaohsiung Medical University
    • Department of Biological Science and TechnologyNational Chiao Tung University
    • Faculty of Medicinal and Applied ChemistryKaohsiung Medical University
Original Paper

DOI: 10.1007/s00775-008-0445-9

Cite this article as:
Chen, T., Cheng, T., Chen, C. et al. J Biol Inorg Chem (2009) 14: 253. doi:10.1007/s00775-008-0445-9

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 T2-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 oxideHerceptinHER2/neu receptorMagnetic resonance imaging

Supplementary material

775_2008_445_MOESM1_ESM.pdf (116 kb)
Supporting information (PDF 116 kb)

Copyright information

© SBIC 2008