Therapeutic Nanoparticles Give New Meaning to Sugar-Coating Medicine

Published on 22 September 2009

A research team at the National Institute of Standards and Technology (NIST) studying sugar-coated nanoparticles for use as a possible cancer therapy has uncovered a delicate balancing act that makes the particles more effective than conventional thinking says they should be. Just like individuals in a crowd respecting other people’s personal space, the particles work because they get close together, but not too close.

In cooperation with colleagues at The Johns Hopkins University, Dartmouth College, the University of Manitoba and two biopharmaceutical companies, the NIST team has demonstrated* that the particles—essentially sugar-coated bits of iron oxide, about 100 nanometers wide—are potent cancer killers because they interact with one another in ways that smaller nanoparticles do not. The interactions, thought by many bioengineers to be undesirable, actually help the larger particles heat up better when subjected to an alternating magnetic field. Because this heat destroys cancer cells, the team’s findings may help engineers design better particles and treatment methods.

Nanoparticles hold the promise of battling cancer without the damaging side effects of chemotherapy or radiation treatment. Minuscule balls of iron oxide can be coated with sugar molecules making them particularly attractive to resource-hungry cancer cells. Once the particles are injected, cancer cells would then ingest them, and doctors would then be able to apply an alternating magnetic field that causes the iron oxide centers to heat, killing the cancer but leaving surrounding tissue unharmed.

Two biotech companies, Micromod Partikeltechnologie and Aduro BioTech, created particles that showed great potential in treating cancers in mice, and they asked NIST to help understand why it worked so well. “But they sent us particles that were much larger than what the conventional wisdom says they should be,” says NIST materials scientist Cindi Dennis. “Larger particles are more strongly magnetic and tend to clump together, which makes them large enough to attract the body’s defense systems before they can reach a tumor. The companies’ nanoparticles, however, did not have this problem.”

Neutron scattering probes at the NIST Center for Neutron Research revealed that the particles’ larger iron oxide cores attract one another, but that the sugar coating has fibers extending out, making it resemble a dandelion—and these fibers push against one another when two particles get too close together, making them spring apart and maintain an antibody-defying distance rather than clumping. Moreover, when the particles do get close, the iron oxide centers all rotate together under the influence of a magnetic field, both generating more heat and depositing this heat locally. All these factors helped the nanoparticles destroy breast tumors in three out of four mice after one treatment with no regrowth.

An iron-centered nanoparticle (left) analyzed at NIST’s Center for Neutron Research has a coating of the sugar dextran, whose tendrils prevent groups of the particles from clumping. When tumor cells ingest them (right), the particles still congregate closely enough to share heat when stimulated by a magnetic field, killing the cells. White arrow indicates a red blood cell. View hi-resolution image
Credit: (l.) J. Aarons; (r.) A. Guistini, R. Strawbridge and P. Hoopes, Dartmouth College

“The push-pull is part of a tug of war that fixes the distance between nanoparticles,” Dennis says. “This suggests we can stabilize interacting particles in ways that potentially pay off in the clinic.”

The research was funded by the U.S. Army Medical Research and Materiel Command and used facilities supported by the National Science Foundation.

* C.L. Dennis, A.J. Jackson, J.A. Borchers, P.J. Hoopes, R. Strawbridge, A.R. Foreman, J. van Lierop, C. Gruttner and R. Ivkov. Nearly complete regression of tumors via collective behavior of magnetic nanoparticles in hyperthermia. Nanotechnology, 20 (2009) 395103. [doi:10.1088/0957-4484/20/39/395103]

Contact: Chad Boutin, boutin@nist.gov, (301) 975-4261

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Small springs could provide big power

Carol Livermore, associate professor of mechanical engineering, left, stands with graduate student Frances Hill in Livermore's lab.
Photo - Patrick Gillooly

September 21, 2009

Mechanical engineer Carol Livermore and colleagues find that carbon nanotubes, used as springs, have potential to compete with batteries for energy storage.

David L. Chandler, MIT News Office

New research by MIT scientists suggests that carbon nanotubes — tube-shaped molecules of pure carbon — could be formed into tiny springs capable of storing as much energy, pound for pound, as state-of-the-art lithium-ion batteries, and potentially more durably and reliably.

Imagine, for example, an emergency backup power supply or alarm system that can be left in place for many years without losing its "charge," portable mechanical tools like leaf blowers that work without the noise and fumes of small gasoline engines, or devices to be sent down oil wells or into other harsh environments where the performance of ordinary batteries would be degraded by temperature extremes. That's the kind of potential that carbon nanotube springs could hold, according to Carol Livermore, associate professor of mechanical engineering. Carbon nanotube springs, she found, can potentially store more than a thousand times more energy for their weight than steel springs.

Two papers describing Livermore and her team's findings on energy storage in carbon nanotube springs have just been published. A paper describing a theoretical analysis of the springs' potential, co-authored by Livermore, graduate student Frances Hill and Timothy Havel SM ’07, appeared in June in the journal Nanotechnology. Another paper, by Livermore, Hill, Havel and A. John Hart SM ’02, PhD ’06, now a professor at the University of Michigan, describing laboratory tests that demonstrate that nanotubes really can exceed the energy storage potential of steel, appears in the September issue of the Journal of Micromechanics and Microengineering.

Theoretical analysis shows the carbon nanotube springs could ultimately have an energy density — a measure of the amount of energy that can be stored in a given weight of material — more than 1,000 times that of steel springs, and comparable to that of the best lithium-ion batteries.

With a snap or a tick-tock

For some applications, springs can have advantages over other ways of storing energy, Livermore explains. Unlike batteries, for example, springs can deliver the stored energy effectively either in a rapid, intense burst, or slowly and steadily over a long period — as exemplified by the difference between the spring in a mousetrap or in a windup clock. Also, unlike batteries, stored energy in springs normally doesn't slowly leak away over time; a mousetrap can remain poised to snap for years without dissipating any of its energy.

For that reason, such systems might lend themselves to applications for emergency backup systems. With batteries, such devices need to be tested frequently to make sure they still have full power, and replace or recharge the batteries when they run down, but with a spring-based system, in principle "you could stick it on the wall and forget it," Livermore says.

Livermore says that the springs made from these minuscule tubes might find their first uses in large devices rather than in micro-electromechanical devices. For one thing, the best uses of such springs may be in cases where the energy is stored mechanically and then used to drive a mechanical load, rather than converting it to electricity first.

Any system that requires conversion from mechanical energy to electrical and back again, using a generator and then a motor, will lose some of its energy in the process through friction and other processes that produce waste heat. For example, a regenerative braking system that stores energy as a bicycle coasts downhill and then releases that energy to boost power while going uphill might be more efficient if it stores and releases its energy from a spring instead of an electrical system, she says. In addition to the direct energy losses, about half the weight of such electromechanical systems currently is in the motor-generator used for the conversion — something that wouldn't be needed in a purely mechanical system.

One reason the microscopic tubes lend themselves to being made into longer fibers that can make effective springs is that the nanotube molecules themselves have a strong tendency to stick to each other. That makes it relatively easy to spin them into long fibers — much as strands of wool can be spun into yarn — and this is something many researchers around the world are working on. "In fact," Livermore says, the fibers are so sticky that "we had some comical moments when you're trying to get them off your tweezers." But that quality means that ultimately it may be possible to "make something that looks like a carbon nanotube and is as long as you want it to be."

Tough and long-lasting

Carbon nanotube springs also have the advantage that they are relatively unaffected by differences in temperature and other environmental factors, whereas batteries need to be optimized for a particular set of conditions, usually to operate at normal room temperature. Nanotube springs might thus find applications in extreme conditions, such as for devices to be used in an oil borehole subjected to high temperature and pressure, or on space vehicles where temperature can fluctuate between extreme heat and extreme cold.

"They should also be able to charge and recharge many times without a loss of performance," Livermore says, although the actual performance over time still needs to be tested.

Livermore says that to create devices that come close to achieving the theoretically possible high energy density of the material will require plenty of additional basic research, followed by engineering work. Among other things, the initial lab tests used fibers of carbon nanotubes joined in parallel, but creating a practical energy storage device will require assembling nanotubes into longer and likely thicker fibers without losing their key advantages.

"These scaled-up springs need to be large (i.e., incorporating many carbon nanotubes), but those individual carbon nanotubes need to work well enough together in the overall assembly of tubes for it to have comparable properties to the individual tubes," Livermore says. "This is not easy to do."

Rod Ruoff, professor of mechanical engineering at the University of Texas, adds that while the theoretical energy density of such systems is high, present ways of making carbon nanotubes are limited in their ability to produce highly concentrated bundles, and so "It appears to me that the 'low hanging fruit' here is to find important applications where the energy density on per weight basis outweighs the energy density on a per volume basis." But, he adds, if Livermore and her team are able to produce denser bundles of carbon nanotubes, "then there are exciting possibilities for mechanical energy storage" with such systems.

The group has already filed for a patent on the technology. Their work has been funded by the Deshpande Center for Technological Innovation Ignition grant and by an MIT Energy Initiative seed grant.

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Carbon nanotubes could make efficient solar cells

September 10th, 2009 By Anne Ju

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In a carbon nanotube-based photodiode, electrons (blue) and holes (red) - the positively charged areas where electrons used to be before becoming excited - release their excess energy to efficiently create more electron-hole pairs when light is shined on the device. Image: Nathan Gabor

(PhysOrg.com) -- Cornell researchers fabricated, tested and measured a simple solar cell called a photodiode, formed from an individual carbon nanotube.

Using a carbon nanotube instead of traditional silicon, Cornell researchers have created the basic elements of a solar cell that hopefully will lead to much more efficient ways of converting light to electricity than now used in calculators and on rooftops.

The researchers fabricated, tested and measured a simple solar cell called a photodiode, formed from an individual carbon nanotube. Reported online Sept. 11 in the journal Science, the researchers -- led by Paul McEuen, the Goldwin Smith Professor of Physics, and Jiwoong Park, assistant professor of chemistry and chemical biology -- describe how their device converts light to electricity in an extremely efficient process that multiplies the amount of electrical current that flows. This process could prove important for next-generation high efficiency solar cells, the researchers say.

"We are not only looking at a new material, but we actually put it into an application -- a true solar cell device," said first author Nathan Gabor, a graduate student in McEuen's lab.

The researchers used a single-walled carbon nanotube, which is essentially a rolled-up sheet of graphene, to create their solar cell. About the size of a DNA molecule, the nanotube was wired between two electrical contacts and close to two electrical gates, one negatively and one positively charged. Their work was inspired in part by previous research in which scientists created a diode, which is a simple transistor that allows current to flow in only one direction, using a single-walled nanotube. The Cornell team wanted to see what would happen if they built something similar, but this time shined light on it.

Shining lasers of different colors onto different areas of the nanotube, they found that higher levels of photon energy had a multiplying effect on how much electrical current was produced.

Further study revealed that the narrow, cylindrical structure of the carbon nanotube caused the electrons to be neatly squeezed through one by one. The electrons moving through the nanotube became excited and created new electrons that continued to flow. The nanotube, they discovered, may be a nearly ideal photovoltaic cell because it allowed electrons to create more electrons by utilizing the spare energy from the light.

This is unlike today's solar cells, in which extra energy is lost in the form of heat, and the cells require constant external cooling.

Though they have made a device, scaling it up to be inexpensive and reliable would be a serious challenge for engineers, Gabor said.

"What we've observed is that the physics is there," he said.

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