Magnetic nanoparticles coated with a specialized targeting molecule were able to latch on to cancer cells in mice and drag them out of the body. The results are described in a study published online this month in the Journal of the American Chemical Society. The study's authors, researchers at Georgia Institute of Technology, hope that the new technique will one day provide a way to test for--and potentially even treat--metastatic ovarian cancer.
"It's a fairly novel approach, to use magnetic particles in vivo to try to sequester cancer cells," says Michael King, an associate professor of biomedical engineering at Cornell University, who was not involved in the study.
With ovarian cancer, metastasis occurs when cells slough off the primary tumor and float free in the abdominal cavity. If researchers could use the magnetic nanoparticles to trap drifting cancer cells and pull them out of the abdominal fluid, they could predict and perhaps prevent metastasis. Although the nanoparticles were tested inside the bodies of mice, the authors envision an external device that would remove a patient's abdominal fluid, magnetically filter out the cancer cells, and then return the fluid to the body. After surgery to remove the primary tumor, a patient would undergo the treatment to remove any straggling cancer cells. The researchers are currently developing such a filter and testing it on abdominal fluid from human cancer patients.
"It's possible that the particles may not ever have to go into the patient's body," says John McDonald, chief scientific officer of the Ovarian Cancer Institute at Georgia Tech and a senior author of the paper. "That would be preferable, because then you don't have to worry about any potential toxicity."
The particles, which are just 10 nanometers or less in diameter, have cobalt-spiked magnetite at their core. Most of the time they are not magnetic, but when a magnet is present, they become strongly attracted to it. On the surface of the particles is a peptide--a small, proteinlike molecule--designed to attach to a marker that protrudes from most ovarian cancer cells.
To test the new technology, the researchers injected first cancer cells and then the magnetic nanoparticles into the abdominal cavities of mice. The cancer cells were tagged with a green fluorescent marker, and the nanoparticles with a red one. When the team brought a magnet near each mouse's belly, a concentrated area of green and red glow appeared just under the skin, indicating that the nanoparticles had latched on to the cancer cells and dragged them toward the magnet.
While this experiment showed that the nanoparticles could snag at least some cancer cells within the body, it's not yet clear what proportion of cancer cells were captured and removed. Tests to pinpoint that proportion are planned.
Cornell's King suspects that the technology may be better suited to diagnosing, rather than treating, metastasis. "I think that this technology has much more potential for diagnostics and for detecting cancer cells," he says. "I'm not fully convinced that it could be used to really significantly filter out cancer cells as a therapy."
A similar technology that uses antibody-coated beads to separate out cancer cells has already proved effective in vitro, but the new study's authors believe that the magnetic nanoparticles will be less likely to cause an unwanted immune response and are thus better suited for use inside the body. And because they seem to bind more strongly than antibodies to their targets, says McDonald, they may be better able to pull out cancer cells.
"The ideal would be to try to get everything, but I doubt that would happen," says McDonald. "But we believe that we could significantly reduce the number and thus lower the probability of metastasis."
For now, the treatment seems uniquely suited to ovarian cancer; most other tumors metastasize through cells floating in the bloodstream rather than in the abdominal fluid. But eventually, the team hopes to adapt the particles for use in blood, perhaps extending their use not only to other cancer types, but also to viral diseases such as HIV. To do so, say the researchers, they will need to develop highly specific targeting molecules for each disease to ensure that healthy blood cells are spared.
To test the feasibility of using the nanoparticles in the bloodstream, Ken Scarberry, a graduate student at Georgia Tech and coauthor of the study, reports watching them in action in an artificial circulatory system that passed under a fluorescent microscope. When a magnet was placed near the microscope's lens, "you could see that all of the cells immediately got sequestered over to the side and did not move as the fluid continued to flow," says Scarberry. "This technology has so many possibilities. Right now, I think we're just scratching the surface with it."