Journal
JOURNAL OF BIOLOGICAL INORGANIC CHEMISTRY
Volume 14, Issue 2, Pages 253-260Publisher
SPRINGER
DOI: 10.1007/s00775-008-0445-9
Keywords
Superparamagnetic iron oxide; Herceptin; HER2/neu receptor; Magnetic resonance imaging
Funding
- National Science Council of the Republic of China [NSC 96-2627-M-037-001, NSC 97-2623-7-037-001-NU]
- National Health Research Institutes [NHRI-EX-95-9424EI]
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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.
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