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

Abstract A novel magnetic resonance imaging (MRI) contrast agent containing Herceptin is reported. The sur-faces 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 magneti-zation (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–nanoparti-cles 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 accu-mulation 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–nanoparti-cles 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