Cancer nanotechnology, where miniscule molecules are designed with literally atomic precision to combat a disease that kills millions every year, is gaining credibility as the next cure for cancer.

"It's 21st-century medicine," said Vicki Colvin of Rice University's Center for Nanoscale Science and Technology. "It sits at the intersection of some of the greatest achievements in many different areas of science, from material science to cell biology to physics and advances in imaging."

Indeed, the National Cancer Institute, which recently announced two waves of funding for nanotech training and research, sees nanotechnology as vital to its stated goal of "eliminating suffering and death from cancer by 2015."

To anyone familiar with the long, often fruitless search for cancer's cure, or the unfulfilled promise of nanotechnology, this may seem far-fetched. But in recent years, scientists have learned more about how cancer works at the cellular level. They have also learned to build molecules that could detect and destroy cancer cells, making today's painful and often-ineffective treatments a thing of the past.

Though the jump from lab to patient is long, scientists are confident that it can be made.

"Developing any drug or diagnostic is a long process, and that's still going to be the case," said Greg Downing, director of the Office of Technology and Industrial Relations at the National Cancer Institute. "But these technologies have the potential to overcome challenges we can't overcome now."

The technologies now being developed are not the complex miniature machines usually associated with nanotechnology, but particles a few nanometers wide. (As a point of reference, the average human hair is about 100,000 nanometers wide, and a red blood cell is 4,000 nanometers in diameter.)

The first cancer nanotech applications will likely involve detection. Nanoparticles could recognize cancer's molecular signatures, gathering the proteins produced by cancerous cells or signaling the presence of telltale genetic changes. Researchers have already used a protein called albumin -- considered a naturally occurring nanoparticle -- to detect proteins found in ovarian cancer tissue.

Other nanoparticles could adhere to cancerous cells and, when viewed under a magnetic resonance imager or fluorescent light, reveal cancers now hidden to our eyes.

"Nanotech gives us the opportunity to detect cancer tumors at 1,000 cells, whereas we're now seeing them at 1 million cells. By the time you detect some cancers today, there's no option of curing them, only of prolonging life," said Sri Sridhar, director of Northeastern University's Nanomedicine Science and Technology Program.

While diagnostic nanoparticles will first be used to analyze blood or tissue samples outside the body, they could eventually be injected into the bloodstream (making it possible to also design particles that will be flushed from the patient unless they stick to cancer cells). But nanoparticles can be made not only to find those cells, but to destroy them.

One such application involves metallic molecules that adhere to cancer cells and can then be heated with microwaves, a magnetic field or infrared light, destroying the tumor while leaving surrounding tissues unharmed. Researchers at Rice University have done just this with gold-coated particles and breast cancer tissue cultures.

Also promising is the design of molecular envelopes for chemical compounds that would otherwise be toxic to ingest. Another possibility, as seen in the National Cancer Institute's video, are nanoparticles that carry therapeutics on their surfaces.

Researchers at the University of Michigan have already treated liver cancer in mice with drug-carrying nanoparticles that lodged in the tumor cells' folic acid receptors.

"We've become very good at building nanoparticles decorated with biological particles, from DNA to proteins," said Bob Langer, a professor of chemical and biochemical engineering at the Massachusetts Institute of Technology, whose lab is currently researching ovarian cancer.

Researchers also hope to make particles that combine all these functions. "We call this the mother ship," said Sadik Esener, an electrical and computer engineering professor at the University of California, San Diego. "You can put multifunctional particles on it, like an aircraft carrier transports choppers and planes. It goes into the body, and if it encounters a suspicious region, finds out what that area is about and delivers the therapeutics."

No less important is nanotechnology's possible use in collecting information about molecular processes. Combined with information about how cells and tissues interact, this could produce detailed digital models of cancer.

"We want to have quantitative computer simulations that will actually predict how a tumor will evolve in a patient," said Vito Quaranta, a cancer biology professor at Vanderbilt University's Integrative Cancer Biology Center. "One of the major problems today is that we're not capable of knowing to what extent and when a particular cancer will be invasive -- when it will spread from prostate to bone, lung to brain. It's the invasion that kills."

Physicians could use this knowledge to guide their treatment. Moreover, said Quaranta, they might even be able to predict a therapy's outcome by simulating how it would modify the tumor over time, perhaps even looking years into the future.

How soon these cancer nanotechnologies will be commercially available is hard to guess. Though the NCI's Cancer Nanotechnology Plan calls for clinical trials on out-of-body applications within three years, and trials on in-body therapies and diagnostics within five years, researchers are cautious about promising too much.

"There's a lot of what I call the 'wow factor' here," said Colvin. "It's a long road ahead of us."

Beyond the inevitable difficulty of duplicating laboratory results in patients, universal standards for ensuring the uniformity and quality of nanoparticles are still being devised. Nanoparticles will also be harder to test than traditional pharmaceuticals, which are better characterized, less complex and interact with tissues in different ways.

"Toxicology testing is really problematic," said Robert Best, a geneticist and bioethicist at the University of South Carolina's NanoCenter. "As you approach this size range, surface chemistry and quantum effects start to get figured in."

However, given the inadequacy of most present treatments, toxicity is not always the most pressing concern, especially for individuals who have aggressive, highly lethal cancers.

"We're not talking about treating high cholesterol," said Best. "We're talking about cancer, and there's some we can't stop with the agents at hand."

Reference Source 141
November 8, 2005