Researchers hope to turn nanotechnology into therapeutic reality
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BY MARK ANDERSEN / Lincoln Journal Star
Lanky molecules poke out from the sides like children's arms from an unsupervised school bus. It's a gangly bit of contraption, an artful wad of protein, metal and medicine.
Gangly, yet sophisticated.
While circulating in the bloodstream, its tiny molecular arms can latch tightly onto cancer cells, and once attached, this bit of nothing — so small it wouldn't trip an ant — becomes both bomb and homing beacon.
In MRI scans, its metallic elements glow brightly, revealing tumors it has latched onto smaller than dust particles. That contact with cancer cells, meanwhile, loosens the polymer bonds securing its poison payload.
If some of the MRI homing beacons stop signaling tomorrow as the body removes the now dead cancer cells, doctors will know the chemotherapy is working. If not, they can alter the payload for a new injection.
In September, the National Cancer Institute announced a $144 million, five-year initiative aimed at developing this and other nanotechnology medical fantasies into therapeutic reality. Within a decade, scientists hope, nano devices will transform medication delivery, and not just for cancer but Alzheimer's, Parkinson's and other age-old afflictions.
Within weeks of the National Cancer Institute's funding announcement, the University of Nebraska Medical Center in Omaha announced it was forming a Center for Drug Delivery and Nanomedicine. Alexander (Sasha) Kabanov, the center's director, is optimistic his team of 31 researchers — assembled from a variety of scientific disciplines at UNMC, the University of Nebraska-Lincoln and Creighton University — will latch onto some of this new cash to further research into polymer micelles, nanogels and other drug delivery devices 100,000 times smaller than the head of a pin.
Nanotechnology, the creation of things measuring billionths of a meter, isn't as futuristic as most people think, said Kabanov, a Russian scientist who brought his research to Nebraska after the collapse of the Soviet Union. "Actually, we are using it on patients right now," he said. "We can help people today."
Kabanov's team began forming in the early 1990s as an offshoot of the UNMC College of Pharmacy. Their research led to Supratek Pharma's current clinical trials of a nanotechnology device for treating esophageal adenocarcinoma. If successful, the device — a micelle — may be used to treat other cancers.
Micelles
Chances are, you covered yourself with self-forming micelles this morning in the shower. Normally called soap, these micelles formed when chemical forces caused tiny cores of water-repellent material to be surrounded by outer shells of water-soluble material. Soap cleans by trapping the body's grease in the oily core. The watery outside allows it to be washed away.
Kabanov's micelles aren't soap.
Instead, a water-repellent core of medicine is surrounded by a protective water-soluble exterior. These micelles, research shows, can defeat drug-resistant cancer cells. The discovery came as an offshoot of learning to make drugs penetrate the blood-brain barrier.
That barrier, Kabanov explained, is actually an array of tiny chemical pumps in the walls of the capillaries that carry blood within the brain. These pumps allow blood to pass and feed nerve cells, but most foreign invaders get pushed back into the bloodstream.
The pumps use the same fuel as the body's muscles. Polymer micelles cause these pumps to exhaust that fuel, enabling more medication to pass.
Drug-resistant cancer cells protect themselves in the same way, he said. The cell pumps the medicine back outside, enabling the cell to survive. Combining a cancer drug with polymers, he said, makes it 1,000 times more effective against medication-resistant cells — at least in laboratory experiments.
UNMC scientist Joe Vetro explained another strategy that tries to exploit a cancer's physical properties and make it a weakness.
Like babies in the womb, he said, cancer tumors grow their own blood vessels. Without them, they couldn't grow so much. The strategy is to stop the cancer growth by preventing vessels from forming.
The trick is to concentrate an antidote to this vessel growth inside the tumor. UNMC scientists encase the antidote in nanogels small enough to enter the tumor but too large to exit its poorly developed lymphatic drain. As a result, the antidote accumulates like rain water in a basement without a sump pump.
Other nanotechnology strategies would marry metals onto cancer-seeking antibodies.
Ultimately, several devices might be combined into the multifunctional contraption described above — a device that seeks out, exposes problems and fixes or destroys them.
A small need
Announcing its research initiative, the National Cancer Institute said research into genetic science was suggesting new ways to defeat cancer but turning those theories into therapies would require mechanisms able to reach into individual cells and fix them. Cells are one thing that nanotechnology can get its arms around.
There remain many bodily defenses and technical challenges to overcome, but there are advantages to working small. At these sizes, it's possible to control a material's fundamental characteristics, such as melting point, magnetism and color, without changing its basic composition.
Metal can be fused to amino acids. DNA segments can be joined to synthetics.
Future nanotechnology devices might some day act like tiny surgeons or computer programmers, splicing errant segments of genetic code while it's inside a living cell.
That's in the future. Introducing DNA into a cell remains a very tricky problem.
"Who said that it's easy?" Kabanov said.
One goal of his team is to develop modular solutions, the ability to adapt one strategy for confronting a variety of diseases. Eventually, it should be possible to mix and match anticancer drugs with any number of nanotechnology delivery vehicles and targeting agents.
That would allow doctors to fine-tune a therapy as needed, said UNMC researcher Tatiana Bronich. A disease takes as many different forms as there are patients who have it, she said.
"It's never the same disease. Even aspirin acts very differently in different people."
Even the effectiveness of existing drugs might be improved.
Traditional chemotherapies act like weed killers, poisoning every cell in the body to kill the faster growing, more susceptible cancer cells. Nano devices could bypass the healthy cells and target the sick.
There are many problems with traditional drug delivery, Kabanov said. The body eliminates many before they can work, the body degrades some drugs, some drugs can't penetrate cancer tumors, and bodily tissues develop resistance to drugs. Nano devices can preserve, protect and disguise.
Nano Nebraska
In the early 1990s when he first became involved, Kabanov said, few scientists were working on these problems. Today, there are many.
Since 1995, the UNMC program has garnered 27 grants worth
$13.4 million from the National Institute of Health and National Science Foundation.
Nebraska's program has earned some small recognition, Kabanov said.
"It wouldn't be an exaggeration to say we are well on the map in this place," he said.
The aspirations are to build much bigger. The goal is not to perfect today's infant technologies, he said, but to look 15 years down the road at the new solutions that will be needed.
At the same time, Kabanov hopes to develop things that will benefit people within his lifetime. Most scientific discovery is about laying the groundwork for future scientists. It's hard to do something that makes a difference in your own lifetime, he said.
It might be a small distinction, but, "that's the soul of this program."
Reach Mark Andersen at 473-7238 or mandersen@journalstar.com.
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