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
Original Paper

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 oxide Herceptin HER2/neu receptor Magnetic resonance imaging 

Notes

Acknowledgements

We are grateful to the National Science Council of the Republic of China for financial support under contracts no. NSC 96-2627-M-037-001 and NSC 97-2623-7-037-001-NU. This research was also supported in part by grants from National Health Research Institutes under contract no. NHRI-EX-95-9424EI.

Supplementary material

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

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Copyright information

© SBIC 2008

Authors and Affiliations

  • Ting-Jung Chen
    • 1
  • Tsan-Hwang Cheng
    • 2
  • Chiao-Yun Chen
    • 3
    • 4
  • Sodio C. N. Hsu
    • 5
  • Tian-Lu Cheng
    • 6
  • Gin-Chung Liu
    • 3
    • 4
  • Yun-Ming Wang
    • 1
    • 5
  1. 1.Department of Biological Science and TechnologyNational Chiao Tung UniversityHsinchuTaiwan
  2. 2.Department of Biological Science and TechnologyChung Hwa University of Medical TechnologyTainan CountyTaiwan
  3. 3.Department of Medical ImagingKaohsiung Medical University HospitalKaohsiungTaiwan
  4. 4.Department of RadiologyKaohsiung Medical UniversityKaohsiungTaiwan
  5. 5.Faculty of Medicinal and Applied ChemistryKaohsiung Medical UniversityKaohsiungTaiwan
  6. 6.Faculty of Biomedical Science and Environmental BiologyKaohsiung Medical UniversityKaohsiungTaiwan

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