Bold cancer therapy begins crucial trials

In human test, world may soon know if the hype about nanoshells was deserved

By ERIC BERGER Copyright 2008 Houston Chronicle

July 31, 2008, 12:40AM

The buzz surrounding gold nanoshells, a radical new approach to treating cancer, began shortly after their creation in Houston a decade ago.

The work by Rice University scientists prompted U.S. Rep. John Culberson, a nanotechnology enthusiast whose district includes Rice, to declare that cancer was "cured." And when the National Institute of Cancer announced a massive influx of funding into nanotechnology -- the control of matter on the atomic and molecular scale -- nanoshells became its poster child.

But cancer hasn't been cured, and drugs touted as magic bullets litter the history of cancer research. So what of nanoshells? Are they all sizzle, no substance?

It's a question that's not yet answerable but may be soon. Without fanfare, the Houston company formed to develop nanoshells, Nanospectra Biosciences, has just begun its first human clinical trial, treating a patient with head and neck cancer.

The company hopes to heat nanoshells in the tumor with near-infrared light, burning the cancerous growth away.

For the company and for Houston, the trial marks a big step.

Nanoshells -- tiny spheres of glass coated with gold -- are the first engineered nanomaterial to enter into human trials. And discoveries made in Houston labs are typically developed by biotechnology firms elsewhere, such as Boston or San Diego.

"I'm thrilled," said Naomi Halas, the Rice chemist who created nanoshells in 1997 and realized a few years later their potential to treat cancer. "There's no question it's been a long road, but we always knew it was going to be that way."

The road for any potential medical therapy from a basic science lab into a hospital is always a long and tortuous one.

After conceiving a use for a new technology, a scientist must jump numerous hurdles to reach clinical trials: find medical collaborators, get research funding, obtain venture capital funding, find biotech professionals to create a company that will manufacture the new device or drug, run countless animal tests and finally get U.S. Food and Drug Administration approval for human tests.

And that's just the big stuff, not the countless details.

"Unfortunately, the development of drugs and devices is not at all an efficient process," said Dr. Robert Bast, vice president for translational research at The University of Texas M.D. Anderson Cancer Center.

Classified as a 'device'

On average, it takes nine to 15 years to bring a drug from the laboratory into the clinic, Bast said.

Nanoshells have a key advantage, however. The FDA has classified them a "device" rather than a "drug," because gold does not react with the body. Devices are subject to a streamlined approval process.

It's easy to find drugs that will kill cancer cells. The difficulty has always been twofold: running the drugs past the body's immune system, and then selectively delivering the lethal compounds only to cancer cells and not healthy tissues.

Nanoshells appear to meet both criteria. The body's immune system ignores nanoshells. And because of their tiny size -- about half that of the smallest bacteria -- they're typically only ingested by cancer cells.

That's because the blood vessels that "feed" tumor cells are generally larger and more leaky than healthy cells' blood vessels, allowing nanoshells to slip in.

About 24 hours after an IV injection of nanoshells, tests have shown, about 1 percent of them accumulate in tumors while most of the rest wash out of the body.

Potential 'amazing'

That provides a critical mass for the next phase of treatment. Because of their design, nanoshells are incredibly efficient at absorbing near-infrared light, which isn't visible and normally passes harmlessly through the body.

But when shined over a tumor laden with nanoshells, the tiny devices absorb the energy, heat up and fry the tumor.

"The therapeutic potential has always been amazing," said Jennifer West, a Rice bioengineer who initially worked with Halas to develop nanoshells as a cancer therapy. "In all of the animal studies, from mice through dogs, we've seen tremendously high rates of tumor regression."

The next step, of course, is the biggest one. Of drugs that begin human clinical trials, only 11 percent actually receive FDA approval. The odds are also long for devices.

In the first trials, nanoshells will be used to target head and neck cancers. But there's a reasonable chance they can be used to treat a wide variety of tumors, Halas said.

Iron-core nanoshells

M.D. Anderson researchers John Hazle and R.J. Stafford, for instance, are employing a variety of approaches in an effort to make nanoshells a viable treatment for a range of cancers.

One of their methods, which was announced this week, uses nanoshells with iron in their core. This allows magnetic resonance imaging, or MRI, to track the accumulation of nanoshells throughout the body.

This permits Hazle and Stafford to ensure that nanoshells accumulate only in tumors and not healthy tissues.

In other M.D. Anderson tests of dogs with brain cancer, the nanoshells destroyed tumors without harming the animals' brains.

"There's a lot of potential here, but as of right now. nanoshells aren't yet a panacea for all cancer," Hazle said. "We're going to need to find better delivery and better targeting techniques."

eric.berger@chron.com