But the high hopes for nanomedicine extend far beyond the drugstore. Medicine and nanotechnology are a natural pairing because life itself is a nanoscale phenomenon. Where biology is concerned, the nanoscale is where the action is—amino acids, proteins, DNA, viruses—all are measured in nanometers. The study (and perchance the cure) of disease will increasingly take place where it begins—at the cellular and subcellular level.

The fact that nanomedicine operates at the same scale as our component proteins is cause for sobriety as well as excitement. If little is known so far about the potential for nanoscale medicines to heal, even less is known about their potential to harm. Future research will necessarily walk a careful line, pursuing our hopes for nanomedicine while addressing justifiable concerns.

Among the highest hopes for nanomedicine is nothing less than a cure for cancer. Equally promising is the possibility of extremely targeted and controlled drug delivery, using nanoscale encapsulation methods that are designed to release their medicine at just the right time and place. Nanostructures also seem destined to assist with diagnosis of disease, bringing improvements in imaging and detection of the body’s subtlest biochemical signals.

But what, you ask, has nanomedicine done for us lately? Or more to the point, what will it do for us soon? The most intriguing developments in nanomedicine are still just that—under development. That said, here are a few of the nanomedical technologies that are available now or could become available in the next few years.

• A Cure for Cancer?

• Napkin to Detect Biohazards

• Synthetic Bone

• Color-Changing Tattoo for Diabetics

• Imaging With Quantum Dots

• HIV-Preventative Gel

A Cure for Cancer?

“You’ve got cancer.” There are few medical diagnoses more terrifying. Although some cancers are treatable, survival is far from guaranteed, and currently available therapies—surgery, chemotherapy, and radiation—have a number of highly unpleasant and sometimes fatal side effects. But technologies currently in development strongly suggest that the day is not too far off when “the big C” will no longer be so big a deal.

Traditional chemotherapy and radiation therapies are the medical equivalent of saturation bombing. Healthy cells are killed along with the cancerous ones. The trick to an effective cancer cure is finding a way to target only cancerous cells. That’s where nanotechnology comes in.

A carbon nanotube is a hollow tube consisting of repeating hexagonal arrangements of carbon atoms.

Several varieties of nanostructures are demonstrating extraordinary power to selectively destroy cancerous cells. Nanostructures like carbon nanotubes and gold nanoshells both show promise not only in treating cancer, but also in allowing early, precise, and noninvasive detection of cancer. Carbon nanotubes are rolled-up sheets of carbon atoms, forming hollow tubes only about one nanometer wide. Gold nanoshells are tiny spheres (in this case, of silica) coated with a thin layer of gold.

What’s the trick to getting nanotubes and nanoshells to stick only to cancerous cells? So far, researchers have used both folate (a B vitamin) and antibodies. Cancer cells have an unusually high number of receptors for folate, and nanostructures coated in folate pass easily into cancerous cells. Antibodies promise even greater selectivity; for example, a nanostructure can be coated with antibodies that bind to proteins found only on the surface of melanoma cells.

Once the nanotubes are stuck to the cancerous targets, they are poised to kill in one of two ways. Their hollow interiors can carry anticancer drugs, or they can be zapped with infrared radiation, the same relatively harmless form of radiation that causes sunlight to feel warm and that turns on your TV remotely. Bathed in infrared light, which passes easily through body tissue, the carbon nanotubes heat up dramatically and destroy the attached cancerous cells.

Gold nanoshells appear in this series of photographs, magnified 15,000X, 20,000X, 30,000X, and 95,000X respectively.

Gold nanoshells also show great promise in targeting tumors, even without the help of folate or antibodies to guide them. Thanks to their small size—twenty times smaller than a human blood cell—nanoshells injected into the bloodstream tend to congregate in cancerous tumors, which grow so rapidly and erratically that they tend to have “leaky” blood vessels that let gold nanoshells pass into the cancerous tissue. Apply some infrared radiation from the outside and the nanoshells cook the tumor to death while leaving healthy tissue unharmed.

The fact that nanostructures can be designed to collect at tumor sites makes them very promising for cancer detection, as well. Nanotubes and nanoshells are both good conductors; when they collect around cancerous cells, they can act as beacons to make even tiny tumors visible during scans.

So far, the great promise shown by nanostructures in treating cancer has been limited to Petri dishes and mice. Human trials are likely to begin in the next few years, a prospect that thrills some people even as it makes others nervous.

Despite glimmers of a cancer cure on the horizon, the nanostructure picture isn’t entirely rosy. The ease with which nanostructures can enter cells leaves open the as yet largely unexplored question of what else they might do once inside. Fish exposed to nanostructures called buckyballs developed severe brain damage in one study, and another showed that mice inhaling carbon nanotubes developed lesions in their lungs. Any medical use of nanostructures will require plenty of research to confirm that they can be administered safely.
^back to top

Napkin to Detect Biohazards

Imagine being able to detect harmful bacteria, viruses, or other contaminants with a simple swipe of a paper towel. Far-fetched as it might sound, such a technology already exists, though it’s not yet on the market.

The presence of E. coli bacteria (shown here) causes the "nano napkin" to turn yellow.

The so-called “nano napkin” is a napkin made of ultra-fine polymer fibers 100 billionths of a meter (or 100 nanometers) wide. The fibers are coated with antibody-bearing proteins. When the antibodies come in contact with a specific pathogen, they release a dye that changes the color of the napkin.

So far, researchers have only developed a napkin to detect E. coli bacteria. Wipe the napkin on a surface contaminated with E. coli and it turns yellow—a potentially useful tool in a meat-packing plant or industrial kitchen. By substituting different antibodies, napkins could be made to detect any number of contaminants, including anthrax, bird flu, or even the common cold virus. Multiple antibodies on one napkin could allow for detection of dozens of biohazards at once.

Though the napkin is in its preliminary stages, the technology promises to be inexpensive and, clearly, easy to use.
^back to top

Synthetic Bone

Broken bones, bad backs, torn ligaments—orthopedic ailments and injuries of all kinds often necessitate the use of tissue and devices to replace or temporarily secure real bone.
In some cases, real bone donated from other areas of the body can be used, but the supply is limited. For patients with degenerative bone diseases, bone from elsewhere in the body might not be sufficiently strong.

The need for strength explains why most orthopedic devices to bolster bone are metallic. However, metal screws, pins, and plates can cause inflammation, and bone doesn’t grow back as strongly around metal as it does around other bone. Discomfort caused by metal orthopedic devices can also necessitate follow-up surgeries to remove them after healing is complete.
An optimal replacement for natural bone would be almost indistinguishable from natural bone. It would also be bioabsorbable, meaning that over time, it would be absorbed by the body and replaced by natural bone. Natural bone is largely comprised of nanoscale minerals of hydroxyapatite. Bioabsorbable bone-replacement technologies have been based on this material, but they have used larger-than-nanosized grains, creating a material that is not especially strong.

These implants are made of synthetic nano-engineered bone.

In 2005, however, the FDA approved a nano-engineered synthetic bone that is both bioabsorbable and almost as strong as stainless steel. Formed in the lab by precipitation from a solvent, the translucent material is made up of nanocrystals of hydroxyapatite, the same mineral in natural bone. The impressive strength of the material is due to the small size of the nanocrystals; cracks have a harder time forming between the ultra small crystals. The small size of the crystals also speeds healing and the bioabsorption of the material.

Early applications of the synthetic include an injectable bone filler, screws for holding grafted ligaments in place, anchors to attach sutures to bone for surgeries such as rotator cuff repairs, and implants called fusion cages that help fuse spinal vertebrae together.
^back to top

Color-Changing Tattoo for Diabetics

For millions of diabetics, the need to monitor blood sugar levels means daily needle-sticking to obtain a blood sample. But there is a light—fluorescent, to be exact—at the end of the glucose-monitoring tunnel, in the form of a tattoo that changes color in response to changes in blood sugar levels.

Blood testing is a daily routine for millions of diabetics, but could soon be made unnecessary by a glucose-monitoring tattoo.

The technology relies on injecting an “ink” comprised of tiny fluorescent plastic beads just under the skin. The beads are coated with a molecular compound that recognizes the presence of glucose and glows when exposed to certain frequencies of light. Using a wristwatch monitor, a person would only need to check the color of the tattoo at any time for an accurate blood-sugar-level reading.

The tattoos have already been tested successfully on rats, with no apparent ill effects. Human trials are still several years away, however. Since the fluorescent compounds in the beads do break down over time, the tattoos would probably need to be boosted once a year or so.

Strictly speaking, this application is not a nanotechnology, because the tattoo ink’s fluorescent beads are actually at the “micro” scale. (A nanometer is a billionth of a meter, whereas a micrometer is only a millionth.) However, researchers are exploring plenty of other medical monitoring applications that are at nanometer scale, including a NASA project that would use retinal scanning of fluorescent nanoparticles to detect human exposure to radiation.
^back to top

Imaging with Quantum Dots

In medicine and biomedical research alike, understanding disease requires seeing the invisible. What pathogens are at work, and where are they lurking? Which tissue is diseased or damaged, and which tissue is healthy? How and where is the disease spreading? To answer such questions, or even to be able to understand how the body develops and functions when it’s perfectly healthy, we have to be able to see things—viruses, genetic abnormalities, cellular changes—that can’t easily be seen.

Until recently, researchers often visualized these tiny biomedical players by “tagging” them with organic dye molecules. These dye molecules absorb light of only a very specific frequency and then reemit it. When attached to a subject of interest, they glow with a characteristic color. Unfortunately, these organic dye molecules break down rapidly, quickly losing their ability to glow. Meanwhile, they are also often quite toxic, and so are of limited use for the study of living systems.

Differently-sized quantum dots glow with different colors when exposed to ultraviolet light.

But the future of biomedical imaging is glowing more brightly thanks to quantum dots. Quantum dots are semiconductor nanocrystals—very tiny bits of materials that are not quite metals, and not quite nonmetals. Imagine starting with a small chip of silicon, and then breaking it into smaller and smaller bits. When you have a piece that’s only about 20 nanometers or so across, that’s a quantum dot.

The amazing (and amazingly useful) thing about quantum dots is their flexibility when it comes to both absorbing and emitting light. They can absorb light of all frequencies, above a certain threshold. The light they emit, however, depends on the dot’s size. A smaller dot emits bluer light, a larger dot emits redder light. In this way, a single material such as silicon can be used to make a rainbow of differently-colored quantum dots, each of which can be chemically tailored to bind only to certain specific targets—it’s like having an infinite variety of colored Post-Its^® to paste directly onto cells, viruses, and other biological sites of interest.

Glowing red quantum dots reveal cells infected with a respiratory virus.

Biological systems being as complex as they are, the potential for numerous tags that can all be monitored at once is a great boon. The other advantage of quantum dots for biomedical imaging is a much longer lifetime. Cells can be tagged with a quantum dot and then visualized for several cell generations before they lose that special glow.

In light (ahem) of their advantages, quantum dots are being put to an ever-expanding number of research uses, such as watching the spread of a flu virus through lung tissue or singling out cancerous cells in mice. In the coming years, quantum dots are certain to speed research progress and thereby speed the arrival of cures and treatments. It’s likely that quantum dots will eventually be put to use pinpointing disease sites and identifying pathogens in living humans.
^back to top

HIV-Preventative Gel

Forty million people are infected with HIV worldwide, and the number grows by millions each year. The current best weapons against HIV transmission are barrier methods—condoms and dental dams. Even these are not 100 percent effective, given the possibility that these barriers may rupture.

These T cells are infected with the HIV virus. Soon, HIV infection could be prevented by trapping the HIV virus in a dense, bushy molecule called a dendrimer.

A company in Australia is developing a “liquid condom,” a topical gel called VivaGel that blocks the transmission of HIV as well as other sexually transmitted diseases, including herpes and chlamydia. Applied to the vagina before sex, the gel works by binding to receptors on the surface of the HIV virus, making them unable to attach to (and thereby infect) T cells in the body.

The nanotechnology behind the gel is a tree-like molecule called a dendrimer. Dendrimers are constructed in stages. Starting from a central core, multiple compounds attach and branch off. Further reactions cause each branch to branch in turn, ultimately forming a dense, bushy structure. The ability of dendrimers to conceal drugs within their branches makes them very promising as smart drug delivery capsules, especially since the dendrimers can also be designed to change shape and release their cargo under appropriate conditions.

Multiple branches give dendrimers their tree-like structure.

In the case of the “liquid condom,” however, the dendrimers themselves, and not a drug hidden inside, are the active ingredient. Like balls of Velcro, dendrimers stop infection merely by sticking to the receptors on the surface of the HIV virus and other microbes.

Vivagel has already demonstrated its effectiveness at preventing HIV transmission in primates, and has passed its first round of human testing. The manufacturer hopes to have the product on the market in 2008.
^back to top