Monday, August 4, 2008

Nanomagnets tackle cancer

Technique uses heat to kill cancerous cells
In nanomagnetic cancer treatment, blue fluid with therapeutic nanomagnets targets tumor cells (right). But the nanomagnets leave healthy cells (left) alone. Click on image for full story.MagForce Nanotechnologies

A new wave of therapies can exert a magnetic hold over disease — literally. The therapies employ powerful, roughly spherical magnets to help kill carefully targeted diseased cells and nothing else. What makes these magnets special is their size. Each is about a thousandth the diameter of a human hair.

Most researchers in the field are designing these billionth-of-a-meter-scale magnets to serve as highly localized space heaters. Under the influence of an external magnetic field, the magnetic particles will warm to temperatures that will kill immediately adjacent cells.

Two U.S. research groups recently reported success in developing high-performance iron-cobalt nanomagnets for cancer therapy. New studies by another group describe the ability to target, track and deliver killer heat with a weaker, but potentially less toxic, class of cobalt-free magnetic nanoparticles.

If these nanonuggets and their ilk perform as expected, they should increase cancer survival rates and lower the toxicity associated with conventional therapies. Indeed, MagForce Nanotechnologies AG, based in Berlin, is exploring the idea of making its tiny magnetic beads do double duty: heat-treat tumors in the body and at the same time deliver drugs directly into malignancies. Direct delivery should largely eliminate the poisoning of healthy tissue — a primary side effect of most existing cancer treatments.

Some dozen teams around the world are developing these therapeutic beads, notes Robert Ivkov of Johns Hopkins University in Baltimore. He and others have established the technology’s proof of concept in test-tube and animal studies.

MagForce, the only group to have tested nanomagnet therapy in people, appears closest to commercialization. Over the past five years, it has conducted trials, enrolling patients with at least eight tumor types, according to Uwe Maschek, the company’s chief executive officer. The most advanced trial is currently studying some 65 patients with late-stage, recurrent glioblastoma multiforme, a type of brain cancer. Individuals with this cancer typically survive no more than seven months, he notes.

By next year the company hopes to establish whether its nanomagnetic therapy lengthens survival by at least three months. If it does, Maschek says MagForce could receive regulatory approval to market its technology in the European Union by the first quarter of 2010.

On June 2, Triton BioSystems Inc., Ivkov’s former employer, merged with another company to form Aduro Biotech, based in Berkeley, Calif. The new firm’s website describes a planned 2009 trial that would administer therapeutic nanomagnets to U.S. cancer patients.

MagForce founder Andreas Jordan began exploring nanomagnet cancer treatment some 20 years ago. He aimed to use hyperthermia — essentially inducing highly localized 44° Celsius to 50°C fevers to kill diseased tissue. Not only are cancer cells much more sensitive to heat, but radiation and cancer drugs also tend to work better on heat-stressed cells.

In fact, researchers have long been interested in using heat to treat disease. A research team at Presbyterian-St. Luke’s Hospital in Chicago led by R.K. Gilchrist reported a promising new approach — a full half century ago.

The surgeons injected a fine, iron-oxide powder into lymph nodes suspected of hosting metastases — the seeds of new cancers — and applied a magnetic field to heat the micromagnets. It worked like a charm, the researchers reported in a 1957 Annals of Surgery paper. “The possible application of such a tool,” Gilchrist’s group concluded, “requires little imagination.”

Yet the technology languished for much of the next four decades. Ivkov says it required something that was unusual in the 1950s — research teams that integrated chemists, materials scientists, cell biologists and physicists. Today such collective efforts tailor tinier and more effective magnets, and are perfecting strategies to activate the nanonuggets without burning healthy tissues along the way.

Nearly all research groups work with iron-oxide nanomagnets. But in the April 1 Journal of Applied Physics, Michael McHenry’s group at Carnegie Mellon University in Pittsburgh reported developing a non-oxide iron-cobalt particle with a magnetic strength five to 10 times that of oxide magnets. This could permit treatment using fewer magnetic nanoparticles, McHenry says, or a lower-powered external field to heat the nanobeads.

Ultimately, those beads will receive a coating to shield the potentially toxic cobalt and to keep the nanonuggets from looking like foreign objects that the body should mark for disposal. This coating can also be studded with antibodies to selectively bind to receptors found on the surface of a target, such as a cancer cell.

In a Journal of the American Chemical Society paper posted online in mid-July, Kenneth Scarberry and his colleagues at the Georgia Institute of Technology in Atlanta describe an oxide version of the iron-cobalt recipe for their nanobeads.

They gave their nanomagnets a “sugar coating” of polygalacturonic acid, Scarberry says, and then linked tiny proteinlike structures to the coating. The attached peptides serve as hooks to grab onto a receptor that’s only present on ovarian cancer cells.

The scientists report that by placing a big magnet on the skin of a treated mouse, they can pull injected nanobeads to the other side of the skin, which could facilitate eventual nanobead removal. But the application the researchers are most excited about, Scarberry says, is a dialysis-like system. It would pump liquids from inside the body through a tube outside the body. Nanomagnets treated with ovarian cancer cell “hooks” would line the inside of the tube. The beads would catch and hold passing metastatic cells, filtering the blood before it is returned to the body.

Scientists at the University of California, Davis School of Medicine and the former Triton BioSystems collaborated for several years on related studies using a different nanoparticle model. Instead of creating sugar-coated magnets, they essentially created sugar balls studded throughout with magnetic iron-oxide “raisins,” explains Ivkov.

His group attached antibodies that bind to receptors on breast cancer cells. Then they injected the nanomagnets into mice that had been seeded with those cancer cells and heated the beads for 20 minutes. Tumors in the treated animals shrank. Far more so, in fact, than predicted.

But cancer treatment is far from the only medical application being eyed for these nanomagnets. Scarberry first became interested in the technology a couple of years ago when he realized it might offer a clever adjunct to standard therapy for HIV — the AIDS virus. He won’t say much except that his preliminary data on this “look promising.”