Tag Archives: nanoparticles

Magnetic brain stimulation:New technique could lead to long-lasting localized stimulation of brain tissue without external connections.

By David Chandler


CAMBRIDGE, Mass–Researchers at MIT have developed a method to stimulate brain tissue using external magnetic fields and injected magnetic nanoparticles — a technique allowing direct stimulation of neurons, which could be an effective treatment for a variety of neurological diseases, without the need for implants or external connections.

The research, conducted by Polina Anikeeva, an assistant professor of materials science and engineering, graduate student Ritchie Chen, and three others, has been published in the journal Science.

Previous efforts to stimulate the brain using pulses of electricity have proven effective in reducing or eliminating tremors associated with Parkinson’s disease, but the treatment has remained a last resort because it requires highly invasive implanted wires that connect to a power source outside the brain.

“In the future, our technique may provide an implant-free means to provide brain stimulation and mapping,” Anikeeva says.

In their study, the team injected magnetic iron oxide particles just 22 nanometers in diameter into the brain. When exposed to an external alternating magnetic field — which can penetrate deep inside biological tissues — these particles rapidly heat up.

The resulting local temperature increase can then lead to neural activation by triggering heat-sensitive capsaicin receptors — the same proteins that the body uses to detect both actual heat and the “heat” of spicy foods. (Capsaicin is the chemical that gives hot peppers their searing taste.) Anikeeva’s team used viral gene delivery to induce the sensitivity to heat in selected neurons in the brain.

The particles, which have virtually no interaction with biological tissues except when heated, tend to remain where they’re placed, allowing for long-term treatment without the need for further invasive procedures.

“The nanoparticles integrate into the tissue and remain largely intact,” Anikeeva says. “Then, that region can be stimulated at will by externally applying an alternating magnetic field. The goal for us was to figure out whether we could deliver stimuli to the nervous system in a wireless and noninvasive way.”

The new work has proven that the approach is feasible, but much work remains to turn this proof-of-concept into a practical method for brain research or clinical treatment.

The use of magnetic fields and injected particles has been an active area of cancer research; the thought is that this approach could destroy cancer cells by heating them. “The new technique is derived, in part, from that research,” Anikeeva says. “By calibrating the delivered thermal dosage, we can excite neurons without killing them. The magnetic nanoparticles also have been used for decades as contrast agents in MRI scans, so they are considered relatively safe in the human body.”

The team developed ways to make the particles with precisely controlled sizes and shapes, in order to maximize their interaction with the applied alternating magnetic field. They also developed devices to deliver the applied magnetic field: Existing devices for cancer treatment — intended to produce much more intense heating — were far too big and energy-inefficient for this application.

The next step toward making this a practical technology for clinical use in humans “is to understand better how our method works through neural recordings and behavioral experiments, and assess whether there are any other side effects to tissues in the affected area,” Anikeeva says.

In addition to Anikeeva and Chen, the research team also included postdoc Gabriela Romero, graduate student Michael Christiansen, and undergraduate Alan Mohr. The work was funded by the Defense Advanced Research Projects Agency, MIT’s McGovern Institute for Brain Research, and the National Science Foundation.

In a paper appearing in the Nov. 18 issue of Nature Communications, the researchers demonstrate the use of the particles, which carry distinct sensors for fluorescence and MRI, to track vitamin C in mice. Wherever there is a high concentration of vitamin C, the particles show a strong fluorescent signal but little MRI contrast. If there is not much vitamin C, a stronger MRI signal is visible but fluorescence is very weak.

Illustration: Christine Daniloff/MIT

Two sensors in one

Nanoparticles that enable both MRI and fluorescent imaging could monitor cancer, other diseases.

By Anne Trafton


 

MIT chemists have developed new nanoparticles that can simultaneously perform magnetic resonance imaging (MRI) and fluorescent imaging in living animals. Such particles could help scientists to track specific molecules produced in the body, monitor a tumor’s environment, or determine whether drugs have successfully reached their targets.

 

In a paper appearing in the Nov. 18 issue of Nature Communications, the researchers demonstrate the use of the particles, which carry distinct sensors for fluorescence and MRI, to track vitamin C in mice. Wherever there is a high concentration of vitamin C, the particles show a strong fluorescent signal but little MRI contrast. If there is not much vitamin C, a stronger MRI signal is visible but fluorescence is very weak.

In a paper appearing in the Nov. 18 issue of Nature Communications, the researchers demonstrate the use of the particles, which carry distinct sensors for fluorescence and MRI, to track vitamin C in mice. Wherever there is a high concentration of vitamin C, the particles show a strong fluorescent signal but little MRI contrast. If there is not much vitamin C, a stronger MRI signal is visible but fluorescence is very weak. Illustration: Christine Daniloff/MIT
In a paper appearing in the Nov. 18 issue of Nature Communications, the researchers demonstrate the use of the particles, which carry distinct sensors for fluorescence and MRI, to track vitamin C in mice. Wherever there is a high concentration of vitamin C, the particles show a strong fluorescent signal but little MRI contrast. If there is not much vitamin C, a stronger MRI signal is visible but fluorescence is very weak.
Illustration: Christine Daniloff/MIT

 

Future versions of the particles could be designed to detect reactive oxygen species that often correlate with disease, says Jeremiah Johnson, an assistant professor of chemistry at MIT and senior author of the study. They could also be tailored to detect more than one molecule at a time.

 

“You may be able to learn more about how diseases progress if you have imaging probes that can sense specific biomolecules,” Johnson says.

 

Dual action

 

Johnson and his colleagues designed the particles so they can be assembled from building blocks made of polymer chains carrying either an organic MRI contrast agent called a nitroxide or a fluorescent molecule called Cy5.5.

 

When mixed together in a desired ratio, these building blocks join to form a specific nanosized structure the authors call a branched bottlebrush polymer. For this study, they created particles in which 99 percent of the chains carry nitroxides, and 1 percent carry Cy5.5.

 

Nitroxides are reactive molecules that contain a nitrogen atom bound to an oxygen atom with an unpaired electron. Nitroxides suppress Cy5.5’s fluorescence, but when the nitroxides encounter a molecule such as vitamin C from which they can grab electrons, they become inactive and Cy5.5 fluoresces.

 

Nitroxides typically have a very short half-life in living systems, but University of Nebraska chemistry professor Andrzej Rajca, who is also an author of the new Nature Communications paper, recently discovered that their half-life can be extended by attaching two bulky structures to them.  Furthermore, the authors of the Nature Communications paper show that incorporation of Rajca’s nitroxide in Johnson’s branched bottlebrush polymer architectures leads to even greater improvements in the nitroxide lifetime. With these modifications, nitroxides can circulate for several hours in a mouse’s bloodstream — long enough to obtain useful MRI images.

 

The researchers found that their imaging particles accumulated in the liver, as nanoparticles usually do. The mouse liver produces vitamin C, so once the particles reached the liver, they grabbed electrons from vitamin C, turning off the MRI signal and boosting fluorescence. They also found no MRI signal but a small amount of fluorescence in the brain, which is a destination for much of the vitamin C produced in the liver. In contrast, in the blood and kidneys, where the concentration of vitamin C is low, the MRI contrast was maximal.

 

Mixing and matching

 

The researchers are now working to enhance the signal differences that they get when the sensor encounters a target molecule such as vitamin C. They have also created nanoparticles carrying the fluorescent agent plus up to three different drugs. This allows them to track whether the nanoparticles are delivered to their targeted locations.

 

“That’s the advantage of our platform — we can mix and match and add almost anything we want,” Johnson says.

 

These particles could also be used to evaluate the level of oxygen radicals in a patient’s tumor, which can reveal valuable information about how aggressive the tumor is.

 

“We think we may be able to reveal information about the tumor environment with these kinds of probes, if we can get them there,” Johnson says. “Someday you might be able to inject this in a patient and obtain real-time biochemical information about disease sites and also healthy tissues, which is not always straightforward.”

 

Steven Bottle, a professor of nanotechnology and molecular science at Queensland University of Technology, says the most impressive element of the study is the combination of two powerful imaging techniques into one nanomaterial.

 

“I believe this should deliver a very powerful, metabolically linked, multi-combination imaging modality which should provide a highly useful diagnostic tool with real potential to follow disease progression in vivo,” says Bottle, who was not involved in the study.

 

The research was funded by the National Institutes of Health, the Department of Defense, the National Science Foundation, and the Koch Institute for Integrative Cancer Research.

Source: MIT News

 

Solid nanoparticles can deform like a liquid|Unexpected finding shows tiny particles keep their internal crystal structure while flexing like droplets.

By David Chandler


CAMBRIDGE, Mass–A surprising phenomenon has been found in metal nanoparticles: They appear, from the outside, to be liquid droplets, wobbling and readily changing shape, while their interiors retain a perfectly stable crystal configuration.

The research team behind the finding, led by MIT professor Ju Li, says the work could have important implications for the design of components in nanotechnology, such as metal contacts for molecular electronic circuits.

The results, published in the journal Nature Materials, come from a combination of laboratory analysis and computer modeling, by an international team that included researchers in China, Japan, and Pittsburgh, as well as at MIT.

The experiments were conducted at room temperature, with particles of pure silver less than 10 nanometers across — less than one-thousandth of the width of a human hair. But the results should apply to many different metals, says Li, senior author of the paper and the BEA Professor of Nuclear Science and Engineering.

Silver has a relatively high melting point — 962 degrees Celsius, or 1763 degrees Fahrenheit — so observation of any liquidlike behavior in its nanoparticles was “quite unexpected,” Li says. Hints of the new phenomenon had been seen in earlier work with tin, which has a much lower melting point, he says.

The use of nanoparticles in applications ranging from electronics to pharmaceuticals is a lively area of research; generally, Li says, these researchers “want to form shapes, and they want these shapes to be stable, in many cases over a period of years.” So the discovery of these deformations reveals a potentially serious barrier to many such applications: For example, if gold or silver nanoligaments are used in electronic circuits, these deformations could quickly cause electrical connections to fail.

Only skin deep

The researchers’ detailed imaging with a transmission electron microscope and atomistic modeling revealed that while the exterior of the metal nanoparticles appears to move like a liquid, only the outermost layers — one or two atoms thick — actually move at any given time. As these outer layers of atoms move across the surface and redeposit elsewhere, they give the impression of much greater movement — but inside each particle, the atoms stay perfectly lined up, like bricks in a wall.

“The interior is crystalline, so the only mobile atoms are the first one or two monolayers,” Li says. “Everywhere except the first two layers is crystalline.”

By contrast, if the droplets were to melt to a liquid state, the orderliness of the crystal structure would be eliminated entirely — like a wall tumbling into a heap of bricks.

Technically, the particles’ deformation is pseudoelastic, meaning that the material returns to its original shape after the stresses are removed — like a squeezed rubber ball — as opposed to plasticity, as in a deformable lump of clay that retains a new shape.

The phenomenon of plasticity by interfacial diffusion was first proposed by Robert L. Coble, a professor of ceramic engineering at MIT, and is known as “Coble creep.”  “What we saw is aptly called Coble pseudoelasticity,” Li says.

Now that the phenomenon has been understood, researchers working on nanocircuits or other nanodevices can quite easily compensate for it, Li says. If the nanoparticles are protected by even a vanishingly thin layer of oxide, the liquidlike behavior is almost completely eliminated, making stable circuits possible.

Possible benefits

On the other hand, for some applications this phenomenon might be useful: For example, in circuits where electrical contacts need to withstand rotational reconfiguration, particles designed to maximize this effect might prove useful, using noble metals or a reducing atmosphere, where the formation of an oxide layer is destabilized, Li says.

The new finding flies in the face of expectations — in part, because of a well-understood relationship, in most materials, in which mechanical strength increases as size is reduced.

“In general, the smaller the size, the higher the strength,” Li says, but “at very small sizes, a material component can get very much weaker. The transition from ‘smaller is stronger’ to ‘smaller is much weaker’ can be very sharp.”

That crossover, he says, takes place at about 10 nanometers at room temperature — a size that microchip manufacturers are approaching as circuits shrink. When this threshold is reached, Li says, it causes “a very precipitous drop” in a nanocomponent’s strength.

The findings could also help explain a number of anomalous results seen in other research on small particles, Li says.

The research team included Jun Sun, Longbing He, Tao Xu, Hengchang Bi, and Litao Sun, all of Southeast University in Nanjing, China; Yu-Chieh Lo of MIT and Kyoto University; Ze Zhang of Zhejiang University; and Scott Mao of the University of Pittsburgh. It was supported by the National Basic Research Program of China; the National Natural Science Foundation of China; the Chinese Ministry of Education; the National Science Foundation of Jiangsu Province, China; and the U.S. National Science Foundation.

Source: MIT News Office