Magnets destroy tumours in mice without side effects

Magnetic Nanoparticles Fry Tumors
by TIM WOGAN
From Science NOW

Any parent fretting over a child's fever knows that temperatures just a few degrees above normal can kill. But cancer researchers have now found a way to make high temperatures heal. In a new study, a team found that injecting mice with tiny magnets and cranking up the heat eliminated tumors from the animals' bodies with no apparent side effects.

The idea of killing cancer with heat isn't new. Researchers know that, like normal cells, cancer cells start to die when the mercury rises above 43˚C. The trick is figuring out how to kill the cancer without harming the body's own cells. One promising idea, known as magnetic hyperthermia, involves injecting minuscule "nanoparticles," basically microscopic lumps of iron oxide or other compounds, into tumors to make them magnetic. The patient is put into a magnetic field that reverses direction thousands of times every second. The magnetic nanoparticles are excited by the applied field and begin to get hot, heating and potentially destroying the surrounding cancer tissue. Because healthy tissue is not altered by the magnetic field, it does not heat up and is not damaged.

But the therapy has yet to make its way to the clinic, with only a single reported trial in humans (with modest success). This is largely because conventional nanoparticles interact only weakly with the applied field, so quite a large dose is needed to generate enough heat to damage the tumor. Although nanoparticles aren't particularly toxic, in large quantities they can trigger the body's immune system to attack them, causing allergic reactions.

Nanoscientist Jinwoo Cheon of Yonsei University in Seoul and colleagues set out to create a nanoparticle that would get hotter than traditional nanoparticles so that not as many would need to be injected into the body. They made two-layer nanoparticles, each containing a core of one magnetic mineral inside a shell of another. Because of an esoteric interaction between the two minerals, called exchange coupling, these "core-shell" nanoparticles interacted far more strongly with the magnetic field than do traditional nanoparticles and released up to 10 times as much heat. That means one would need to give only 10% of the original dose to patients to achieve the same degree of hyperthermia as with traditional nanoparticles.

The team tested its technique on three mice whose abdomens had been grafted with cells from human brain cancer. The researchers injected the tumors with core-shell nanoparticles and placed the mice inside a coil of wire (see illustration). They turned on an alternating current in the coil, creating an alternating magnetic field. Although the researchers weren't able to measure the precise temperatures inside the tumors, their estimates are between 43˚ and 48˚C. After 10 minutes, the team removed the mice from the coil and monitored the tumors for the next 4 weeks.

All traces of cancer disappeared from the mice with no apparent side effects, the team reported online 26 June in Nature Nanotechnology. For comparison, another group of mice were treated instead with a single dose of doxorubicin, a traditional anticancer drug. Although it initially shrunk some of the tumors, they grew back to four times their original size by the end of the trial. Heat treatment after an injection of traditional iron oxide nanoparticles had no significant effect on the tumors.

Nanoengineer Naomi Halas of Rice University in Houston, Texas, is impressed. "This group has solved the key impasse that has arrested the development of magnetic nanotherapies, that is, the weak response of the nanoparticle to the applied magnetic field," she says. "I am so happy that more of these types of nanoparticle-based hyperthermal therapies are being developed to increase the arsenal of weapons against cancer."

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Reference
Lee J-H, Jang J-t, Choi J-s, Moon SH, Noh S-h, Kim J-w, Kim J-G, Kim I-S, PArk KI, Cheon J (2011) Exchange-coupled magnetic nanoparticles for efficient heat induction. Nature Nanotechnology doi:10.1038/nnano.2011.95

Abstract
The conversion of electromagnetic energy into heat by nanoparticles has the potential to be a powerful, non-invasive technique for biotechnology applications such as drug release, disease treatment and remote control of single cell functions, but poor conversion efficiencies have hindered practical applications so far. In this Letter, we demonstrate a significant increase in the efficiency of magnetic thermal induction by nanoparticles. We take advantage of the exchange coupling between a magnetically hard core and magnetically soft shell to tune the magnetic properties of the nanoparticle and maximize the specific loss power, which is a gauge of the conversion efficiency. The optimized core–shell magnetic nanoparticles have specific loss power values that are an order of magnitude larger than conventional iron-oxide nanoparticles. We also perform an antitumour study in mice, and find that the therapeutic efficacy of these nanoparticles is superior to that of a common anticancer drug.