UD researcher targets cancer
Tiny nanotubes explode cancer cells like highly selective 'bombs'
Clockwise from top left: A computer image from Panchapakesan's research work shows a sequence using nanotubes to explode and kill cancer cells.
The News Journal/WILLIAM BRETZGER
Balaji Panchapakesan attacks cancer with “nanobombs.”
By VICTOR GRETO
The News Journal
02/24/2006
Five years ago, when Balaji Panchapakesan reached the 19,335-foot summit of Africa's Mount Kilimanjaro in northeastern Tanzania, he felt alone and small.
And blissfully unafraid.
"There is no security net in nature," the 31-year-old University of Delaware assistant professor of electrical and computer engineering says amid the busy clutter of his campus office in one of the corners of DuPont Hall's meandering third floor.
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Breathing the thin African air, looking at the white streak of the Milky Way in the night sky and feeling at times as if lost on a lunar landscape, Panchapakesan says he realized that meaning can be found in the journey -- in this instance, moving somewhere between the smallness of his body and the enormous size of the mountain.
But his body now stands enormous against the nanoworld in which he works. And he seems on the verge of grasping the literally ungraspable.
He and a handful of colleagues and students at UD and at Philadelphia's Thomas Jefferson Medical School have devised a method of exploding cancer cells with "nanobombs." They figured out how to attach unimaginably small single-walled carbon tubes to cancer cells via proteins. When a laser is directed at the tubes, they heat up and explode, killing the cancer cell. Like a cluster bomb, the tube causes a chain reaction that also kills nearby cancer cells.
If the aloneness he felt on Mount Kilimanjaro is an integral part of the human condition, so is searching and researching, Panchapakesan says. "My goal is to search for the meaning and truth of my own life."
That ultimate personal goal has helped fire the imagination of his scientific and engineering work, which has this ambition: To kill cancer cells without killing any cells around them. This is in stark contrast to chemotherapy, which indiscriminately kills everything it touches around the cancer.
The nanotubes are a billionth of a millimeter, much smaller than a cell, and, "Potentially, they can be used on different types of cancer cells, including breaking up blood clots," he says. About 100,000 nanotubes could pack themselves together on the width of one strand of human hair.
So far, Panchapakesan has used them to successfully destroy human breast cancer cells in the laboratory.
Although he and his team are early in their research, they have shown that the method works "in vitro," in an artificial or controlled environment, or cell culture, outside an organism.
The next step will be clinical animal trials, scheduled to begin within the next six months at Thomas Jefferson. Even so, it will be years before the method can be tested on a person.
"He's very imaginative and enthusiastic," says Dr. Eric Wickstrom, professor of biochemistry and molecular biology at Thomas Jefferson. With Panchapakesan, he recently co-authored two papers. Those articles introduced results of their research to fellow scientists. Another article to be published will concern detecting cancer cells. All the papers are published in a journal called Nanobiotechnology.
"He's a great example of the American way of doing science," Wickstrom, 58, says. "Turn loose a young Ph.D. in his lab and let him run with his ideas."
Early interest in anatomy
Born the second of two children in the state of Tamil Nadu in Chennai (formerly Madras) in southern India, Panchapakesan showed a love of science early, and by 14 he wanted to be a doctor.
Never squeamish, he dissected a rat without breaking any of the rodent's blood vessels, impressing his 10th-grade biology teacher.
He loved looking inside.
"It turned me on to all aspects of the body," he says of his interest in anatomy. "I even loved the jargon. I thought I wanted to be a heart or brain surgeon."
But his interests soon broadened. "I liked the whole idea of constructing things, how things came together and worked," he says.
The fact that his father worked for the Madras oil refineries further pushed him toward the more practical and less personally expensive career path of engineering, with the prospect of working and living near his parents.
But it was in undergraduate school at the Regional Engineering College in Rourkela in northeastern India near Calcutta, more than a thousand miles from home, where dreams of going to the United States for graduate school first took shape.
He applied to Georgetown University and the University of Maryland; the latter accepted him, and he came to the United States in 1995 to study.
Cancer cells detected, destroyed
Wickstrom says Panchapakesan contacted him three years ago and told him of the nanotube idea.
Panchapakesan had been reading articles about the microscopic carbon tubes during graduate school and became intrigued by their properties and potential.
Nanotubes are sequences of carbon atoms arranged in a cylinder tube. "If you block an atom out of the bond, the electrical properties change," he says. What fascinated him initially was its strength. "In its world, it's stronger than steel, and more flexible."
His nanotube research seemed a doable fit with Wickstrom's research, which concerned identifying and turning off the genes that cause cancer.
Wickstrom says he knew of nanotubes only through the scientific literature. "I thought it might be nice," he says. "It couldn't hurt to encourage this guy."
The first year, Wickstrom and his students helped Panchapakesan and his students to get proteins or antibodies to attach themselves to the nanotubes. They were grown in mouse blood cancer cells programmed to make a single antibody.
"We checked to see if they were staying on the tubes," he says. "Neither he nor I knew if it would work."
Scientists already knew how to put antibodies on nanotubes to see if they can use them to detect certain proteins that can be the fingerprints of cancer, Wickstrom says.
"The catch is if a protein binds to a nanotube, you can say you detected a protein. His question was if we could bind it to the whole cell."
They could, by adding antibodies to nanotubes, rinsing them off, and then adding cells, which bound to the nanotubes and caused an increase in current. That showed that the cells could bind and get a major increase in current, Wickstrom says.
"You can only see the cancer cell if the antibody specific to a cancer cell attaches to it," he says. "It's a great way to detect the cancer."
The next step is to destroy the cancer cell.
The experiment bloomed further when Panchapakesan and one of Wickstrom's students hit on the idea of forming a sheet of concentrated nanotubes and putting two wells or indentations in that sheet one millimeter apart.
Putting a cluster of human breast cancer cells in each well, they shined the laser light on one well, and it was picked up by the nanotubes "to the point where the tubes exploded in the one millimeter patch," Wickstrom says. "A millimeter away, the cells were untouched and happy and healthy. That's the kind of precision you have to have to attack tumors wrapped around a critical nerve or organ."
Steps toward attacking tumors
Wickstrom's future experimentation with mice, he says, will involve growing a tumor just under its skin, opening it up, applying a nanotube sheet on the tumor, and shining the laser light on it to see if it kills the tumor.
Scientists are many years away from this method becoming a therapeutic treatment: where, with an injection, the nanotubes would enter the bloodstream and find their way to a tumor to attack it.
"I'm worried about toxicity from these flying, whiskerlike particles that might get into the lungs, liver, or anyplace that might be irritating," Wickstrom says. Because the tubes are long, narrow strands, they potentially could block the liver and kidneys from functioning.
Blowing up other cells is easier to control because the explosions of the nanotubes are controlled by the laser.
But that's only one of the problems. There is a chasm between making the nanotubes work in vitro and making them work within a complex organism, says Deni Galileo, a UD assistant professor in biological sciences.
"Tumors don't grow in dishes," he says. "They grow in organisms, and the trick if you're exploding cells is to try not to have [the organism] bleed to death. Cells in dishes don't have blood vessels."
Galileo has been working on developing and studying the migration, or metastasis, of tumors in chicken embryos. His and Panchapakesan's methods may soon meet each other in a tumor growing above a yolk. They're trying to get money for a student to experiment with nanotubes on chick embryos.
It is much simpler to work with chick embryos than with rodents, Galileo says, and it's an essential first step to take the procedure into an organism.
"We had some ideas about making little tumors and injecting the nanobombs into the bloodstream -- to see where they would go, if they're toxic," he says. Another experiment may be "to form tumors on top of the embryo, which makes it easier to explode them because they're not buried in the animal."
Panchapakesan and his team are not the only ones working on using nanotubes -- first discovered only 14 years ago -- to attack cancer cells. At least two others -- Hongjie Dai, a physical chemist at Stanford University, and Naomi Halas, a chemistry professor at Rice University -- have been using slightly different methods with a similar goal of attacking cancer cells.
India's spiritual influence
When he was in sixth grade, Panchapakesan's father gave him a book that changed his life.
"It was a book about a Himalayan yogi's life," he says. "I was skeptical at first, but it wasn't preachy. It was just an open book about his life. It impressed me."
So much so that he seriously thought of becoming a yogi, or practitioner of yoga, sequestered in the Himalayas.
He still practices yoga, if sporadically, thanks to his busy life.
Although not conventionally religious, he describes himself as "spiritual."
"The human mind is much more difficult to explain than the nature of God," he says.
His migration to "the most capitalistic country in the world," he says, is as ironic as his timing in leaving India.
Panchapakesan sees himself as one of the last wave of Indian immigrants to the United States who left in search of a better life. Because now, he says, India is becoming much more like the United States.
In fact, India began moving away from a state-run economy just as he was applying to schools in the United States in the early 1990s, opening its economy to foreign imports and holding a seemingly boundless reserve for potentially outsourced jobs.
Panchapakesan observes these massive changes to his home country each time he visits his parents and friends, about every two years.
"Some of my friends from school make a lot of money now," he says.
But the only money he seems to be interested now is grant money to continue his research -- a form of searching that he performs sequestered in his messy office, plowing through data and e-mail, or in a lab shooting lasers at normally recalcitrant cancer cells.
He previously received a $120,000 grant from the Department of Defense for his cancer work; a $100,000 grant from the National Science Foundation and a $30,000 grant from UD.
But he just hit pay dirt in the past few weeks when he learned the National Science Foundation awarded him its prestigious Faculty Early Career Development Award. Over five years, he will get $400,000 to support his nanotube research.
The prospect of a long journey of discovery doesn't bother him.
"I'll always be searching for something," he says. "That's just me."
Contact Victor Greto at 324-2832 or vgreto@delawareonline.com.
