Artificially engineered magnetic nanoparticles for ultra-sensitive molecular imaging

Iron oxide nanoparticles have shown promise as agents for detecting tumors using magnetic resonance imaging (MRI), but such efforts have been limited by the relatively weak magnetic signal generated by these nanoparticles.

In order to boost this signal, and improve the ability of MRI to detect the smallest tumors, researchers at Yonsei University in Seoul developed a new chemical method for making iron oxide nanoparticles that would enable them to more carefully control the physical and magnetic properties of these particles. As a result of this effort, described in a publication in the journal Nature Medicine, the investigators were able to detect small tumors implanted into mice.

Jinwoo Cheon, Ph.D., who is also a member of Northwestern University’s Nanomaterials for Cancer Diagnostics and Therapeutics Center for Cancer Nanotechnology Excellence, led the team of investigators that explored how various chemical and physical parameters affect the magnetic signal produced by iron oxide nanoparticles. From these studies, the researchers were able to develop a synthetic technique, using high temperatures and organic solvents, that incorporated traces of manganese, cobalt, or nickel into iron oxide nanoparticles of diameters ranging from 6 to 12 nanometers.

Tests on the resulting nanoparticles showed that those containing small amounts of manganese produced a mangetic signal approximately six times stronger than that produced by the iron oxide nanoparticles typically used in MRI studies. The investigators also found that the 12-nanometer-diameter particles generated a magnetic signal that was about 75 percent stronger than the 6-nanometer-diameter particles.

To determine if these manganese-containing iron oxide nanoparticles could better detect cancer cells using MRI, the investigators labeled the nanoparticles with the human cancer-targeting antibody Herceptin. Herceptin, which is used to treat breast cancer, binds to a specific protein, known as HER2/neu that is overexpressed on certain breast and ovarian tumors. For comparison’s sake, the researchers also prepared Herceptin-labeled conventional iron oxide nanoparticles. The researchers then added these labeled nanoparticles to a variety of human cancer cells growing in culture.

These experiments showed that the manganese-containing nanoparticles were able to detect tumor cells producing only minimal amounts of the HER2/neu protein, while conventional iron oxide nanoparticles could only detect those cells producing the most HER2/neu. A follow-up study confirmed that the enhanced sensitivity observed with the manganese-doped nanoparticles resulted from their superior magnetic properties and not because they bound better or in greater numbers to the targeted cancer cells. These studies, the researchers note, uncovered no signs that the nanoparticles were toxic to the cells.

These results prompted the investigators to examine if manganese-doped iron oxide nanoparticles could detect tumors as small as 50 milligrams in mass in mice. The researchers note that tumors of this size cannot be detected using a highly sensitive method that relies on radioactive tracers. However, within an hour of injecting the nanoparticles into the tumor-bearing mice, the researchers were able to readily locate the implanted tumors using MRI. In contrast, even after two hours post-injection, the researchers were unable to locate the tumors when using conventional iron oxide nanoparticles.

This work, which was supported in part by the National Cancer Institute’s Alliance for Nanotechnology in Cancer, is detailed in a paper titled, “Artificially engineered magnetic nanoparticles for ultra-sensitive molecular imaging.” An abstract of this paper is available through PubMed. View abstract.