Nanomedicine: Tiny technology becomes a big topic

When it comes to innovative disease prevention, diagnosis and treatment, the smallest of the small are increasingly driving the development process.

Researchers are working on minuscule therapeutics they hope will intervene before illness develops, nanoparticles that will carry medication directly to diseased cells without affecting healthy ones and imaging technology that will see imperfections at the molecular level.

It's all part of the nanotechnology revolution. It already has reached into many industries and is finding its role in health care. At the moment, the number of nanomedical tools actually in the hands of physicians might not be large, but it is expected to grow exponentially over the next few years.

"It's one of the most exciting frontiers of medicine right now," said Marsha Rappley, MD, professor of pediatrics and human development at Michigan State University. She gave the welcome address at her institution's nanomedicine conference in April. "It will give my patients and give me, as a primary care physician, a wider array of options for treatment of serious illness."

The activity surrounding this new frontier is indicative of the potential many perceive. Publishers have launched a half-dozen medical journals on the subject. Doctors in this field have formed the American Academy of Nanomedicine. The National Institutes of Health has provided funding to several universities to create nanomedicine institutes. And the American Medical Association even featured an educational session on the subject at its Annual Meeting in June.

"We want to be able to tell our patients and our peers that this is what's coming down the road," said Gary L. Woods, MD, an orthopedic surgeon and the member of the AMA Council on Science and Public Health, who moderated the AMA forum. "The sun is still over the horizon, but the dawn is here."

Though still unclear exactly how to define nanomedicine, most describe it as the targeting of therapeutics and diagnostics to the molecular level through the use of nano-sized particles. These specks are smaller than Raquel Welch in the movie "Fantastic Voyage." Millions of them can fit on the head of a pin. The push is to develop ways to guide them exactly where interventions are needed, thereby allowing precision with minimal involvement of healthy tissue.

"We're going to intervene on the scale that disease really works as opposed to trying to beat an ant with a baseball bat, which is what we do now," said David Baskin, MD, residency program director at the Methodist Hospital Neurological Institute in Houston. He researches nanotechnology that could be used in imaging or anti-cancer drug delivery.

Early advances

The area where nanomedicine already is making its mark is that of pharmaceuticals and medical devices. For several years, for instance, Nucryst Pharmaceuticals, has marketed a burn dressing coated with silver nanocrystals. On the drug front, the Food and Drug Administration last year approved Abraxane, which delivers the chemotherapy drug paclitaxel on the back of nanoparticles of albumin.

Both take advantage of the fact that nano-sized substances have different properties than their full-sized counterparts. According to several studies, the burn dressing has a lower risk of infection and doesn't need to be changed as frequently as those that have a more traditionally manufactured silver coating. Abraxane delivers paclitaxel to cancerous cells without the use of a solvent that can be quite toxic. This means that it can be taken in higher doses and could be a more formidable foe to the tumor.

Developments in this area are expected to continue. Specifically, numerous other pharmaceuticals and devices utilizing nanotechnology are in the works. Some attempt to improve the effectiveness of already available drugs. Others are completely new.

The hope is to create ways to get therapy to places in the body that are otherwise inaccessible, to prevent the body's normal defenses from getting in the way before treatments reach targets and to reduce the chance that healthy tissue will be damaged.

"We're still in the honeymoon period in terms of realizing what nanotechnology's great potential will be, but we're seeing some of the first therapeutic products," said Cato T. Laurencin, MD, PhD, professor and chair of orthopedic surgery at the University of Virginia. He is researching the use of nanotechnology to develop devices that may be able to repair soft tissue, such as rotator cuff injuries. "It's probably one of the most rapidly growing areas of science and areas of inquiry."

For many, nanomedicine is the natural extension of the Human Genome Project, which has long offered the promise of personalized medicine. Experts say the Genome Project provided the map. The tools will come from nanomedicine.

"The Genome Project was a fact-finding mission. Now it's up to us ... to go out and do something with those data," said Samuel Wickline, MD, a cardiologist and a professor of medicine, biomedical engineering, physics and cellular biology at Washington University in St. Louis. Dr. Wickline researches the use of nanoparticles to carry drugs that treat cancer and heart disease and is a founder of St. Louis-based Kereos Inc., a biotechnology company which is attempting to commercialize his work.

Not all of these new tools will be therapeutic. Many will have diagnostic applications.

In this area, researchers have developed handheld point-of-care tests that, because of gold nanoparticles combined with DNA, will be able to determine from a drop of blood or body fluid whether a patient has markers for neurodegenerative problems, cardiovascular disease or cancer. The Biobarcode Ultra-sensitive Protein Detection Technology -- which will be marketed by Northbrook, Ill.-based Nanosphere Inc. -- is currently being tested in some hospitals and is expected to be available more widely within the next two years. The makers say it would be less cumbersome than currently used assays because enzyme amplification is not required. These tests sense proteins and other disease markers that are at such low levels that they cannot be detected with current methods.

"What this means is that one can begin to look at markers that one couldn't consider ... with the old tools because of a lack of sensitivity," said Chad Mirkin, PhD, director of the International Institute for Nanotechnology at Northwestern University in Chicago and one of the founders of Nanosphere.

For example, Dr. Mirkin believes that this test could be used to detect markers for Alzheimer's that are at such low levels in the blood that currently available assays would not be sensitive enough to detect them. These tests also could be used to detect the recurrence of cancer at a stage when it is undetectable to other modalities or find indicators of a patient's impending heart attack.

Finding a new image

Researchers also hope to harness the fact that nanoparticles reflect light differently to develop agents that could be used with an array of currently available imaging technology. These new agents would allow the visualization of each individual cell to diagnose disease early. Once the disease is diagnosed and treated, this imaging technology also could be used to ensure that no unhealthy cells are left untreated or, in the case of surgical removal, left behind.

"If you give a chemotherapeutic agent now, we don't know if the tumor is dying," said Mohamed Khan, MD, PhD, a radiation oncologist and member of the AMA Council on Science and Public Health. "We might see a lump shrink or get bigger or stay the same. You can kill a lot of tumor cells and have it stay exactly the same size, but if you are able to image on a molecular level and see the death signals all turn on -- all of a sudden, you can image and quantify exactly how much tumor is being killed rather than just look at a lump shrink or grow over several months."

After diagnosis and treatment are revolutionized by nanomedicine, many of those involved are optimistic that this line of science eventually will be used for prevention, realizing that this purpose is considered a long way off. Still, many imagine nano-sized machines going into a patient's body to clean up plaque in the blood vessels, to destroy viruses before they can create illness or to maintain cell health by not allowing them ever to become cancerous.

"A nano-sized robot or something that will travel through your body -- kind of as a police officer -- checking if everything is OK. When it senses that something is wrong, it has the tools on board that can fix the cells. [It] is an idea that people have envisioned for decades. We're still a long way away, but it is closer to becoming reality," said Maaike Everts, PhD, a research instructor in the Division of Human Genome Therapy at the University of Alabama, Birmingham. She researches the use of gold nanoparticles to deliver cancer therapy.

But while experts say nanomedicine will radically change the tools that physicians use, most are less convinced that it will significantly change how doctors work.

"We're going to still have to listen to a patient tell us what's wrong, and why it's wrong and what they'd like done about it and treat them as people with the best tools we have," said Paul Sieving, MD, PhD, director of the National Eye Institute and co-chair of the NIH's Nanomedicine Roadmap Initiative. "I think nanomedicine might provide those tools."