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Stable RNA Structures Show Promise in Drug Delivery for Cancer Treatment

Last year I covered research led by Peixuan Guo—at the time he was at the University of Cincinnati—in making stable 3D nanostructures out of RNA (ribonucleic acid) that were resistant to the enzymes that chop RNA up within minutes. 

At the time, this was a significant achievement because RNA possesses more flexible capabilities in building structures than does DNA—or would, if they weren't eaten up in short order. With a stable RNA Guo planned on using it in “gearing a powerful nanomotor that packages viral DNA into the protein shells of a bacterial virus named phi29.”

Now Guo is back with his stable RNA—this time at the University of Kentucky—and has developed a nanoparticle made from the material that could help treat cancer and viral infections

The research, which was published in Nano Today, involved building an X-shaped RNA structure in which each arm of the structure could contain different diagnostic and therapeutic packages.

The packages used in this structure were “small interfering RNA for silencing genes, micro-RNA for regulating gene expression, aptamer for targeting cancer cells, or a ribozyme that can catalyze chemical reactions.”

"RNA nanotechnology is an emerging field, but the instability and degradation of RNA nanoparticles have made many scientists flinch away from the research in RNA nanotechnology,” Guo said in the university press release covering the research.  “We have addressed these issues, and now it is possible to produce RNA nanoparticles that are highly stable both chemically and thermodynamically in the test tube or in the body with great potential as therapeutic reagents.”

Of course, there are a number of nanostructures that have proven capable of both diagnostic and therapeutic in the treatment of cancer and other diseases. It’s not clear from the research whether the RNA-based nanoparticles are any more effective than some other nanostructure in these roles.

The research seems instead to focus on what is capable with an RNA nanoparticle that can stay intact long enough to build something from them. Perhaps their “bottom-up” manufacturing capabilities are still being considered for molecular machine systems as the Foresight Institute wished for last year

Searching for Causes of Nanotech Terrorism

 

A year after the near fatal bombing attacks on nanotechnology researchers in Mexico, Nature has published an article that assesses both that specific attack and the broader issue of nanotechnology terrorism

The article provides one of the most thorough reports I have yet seen on the bombing and its causes. There is hardly a single misplayed note in the piece. However, it does omit one large problem contributing to the issue: poor reporting on nanotechnology, mainly in the mainstream press. 

If you want to sell papers—or get page hits—it’s often better to focus on scaring people rather than merely chronicling achievements. With this understanding, there is hardly any mainstream news article published on the subject of nanotechnology today that isn’t compelled to mention “nanotechnology’s downside” as though this effort will somehow bring balance to an article on researchers developing nanoparticles for drug delivery.

As a result, I see a number of articles that purport to explain nanotechnology either put forward the scare screed on how nanotechnology is somehow poised to threaten our personal privacy or how the world will be overrun by nanobots as in the scenario put forward by Eric Drexler and since dismissed by him. 

Talk of nanobots and the “grey goo” that Drexler conjectured would result if they went unchecked brings us back again to the terrorists responsible for the Mexico bombing. Grey goo is at best an extrapolation by a gifted scientist who has since utterly dismissed it as a realistic scenario. But the idea lingers on and it seems to have taken hold in the terrorist group responsible for the Mexico bombings, Individuals Tending Toward the Savage (ITS), and another group of eco-activists who call themselves Action Group on Erosion, Technology and Concentration (ETC, pronounced et cetera). While ETC thinks itself enlightened since it doesn’t blow up innocent people, it harbors the same misperception as ITS about grey goo being an environmental threat.

Ultimately, ITS and ETC are responsible for their own ill-conceived notions and the acts that they carry out because of them. But everyone along the way is responsible too. The Nature article takes scientists to task for their contribution to the confusion that exists. But to the extent scientists are responsible for this confusion, the responsibility mainly resides at the point where they attempt to explain their work to reporters. I have chronicled these crossed wires between journalists and experts before and it’s never a pretty picture. 

On Andrew Maynard’s 20/20 Science blog, Maynard has described some of his own unfortunate exchanges with journalists and went so far as to post a primer on how scientists and journalists should try to speak to one another. That seems to me a step in the right direction.

There is a lot of information out there and journalists have been given the responsibility of imparting much of it. If they get it wrong, they can contribute to people believing they have some kind of justification for sending pipe bombs to people. If they get it right, then we move a little closer to removing the kind of ignorance that would inspire someone to kill the innocent.

Nanoparticle Offers Early-Stage Treatment to Brain Injuries

Researchers at Rice University are reporting success in using a nanoparticle as an emergency treatment for traumatic brain injuries. The research could also improve brain injury treatment for stroke victims and organ transplant patients.

The nanoparticle, which was developed at Rice University, is polyethylene glycol-hydrophilic carbon clusters (PEG-HCC). It's already being tested in cancer treatment, where it has shown itself to be a powerful antioxidant. 

In the current research, the Rice team took PEG-HCC’s effectiveness as an antioxidant one step further, by using it to counter something called reactive oxygen species (ROS)—after a traumatic brain injury, cells release an excessive amount of an ROS called superoxide (SO) into the blood.

The research, which was published in the journal ACS Nano (“Antioxidant Carbon Particles Improve Cerebrovascular Dysfunction Following Traumatic Brain Injury”), found that PEG-HCC provides a balance to the blood counteracting the effects of the SO when the body’s natural enzymes become overwhelmed by the ROS.

“Superoxide is the most deleterious of the reactive oxygen species, as it’s the progenitor of many of the others,” says James Tour, Rice chemist and a co-author of the paper, in the university press release covering the research. “If you don’t deal with SO, it forms peroxynitrite and hydrogen peroxide. SO is the upstream precursor to many of the downstream problems.”

The PEG-HCC treatment is applied after the second burst of free radicals is released in the blood when the patient is resuscitated. “That’s what we can treat: the further injury that happens because of the necessity of restoring somebody’s blood pressure, which provides oxygen that leads to more damaging free radicals,” explains Thomas Kent, the paper’s co-author, a BCM professor of neurology and chief of neurology at the Michael E. DeBakey Veterans Affairs Medical Center in Houston, in the press release.

In the animal studies that have been performed thus far in the research, the treatment has been characterized as “remarkably effective.”

Kent further notes in the press release: “Literally within minutes of injecting it, the cerebral blood flow is back to normal, and we can keep it there with just a simple second injection. In the end, we’ve normalized the free radicals while preserving nitric oxide (which is essential to autoregulation). These particles showed the antioxidant mechanism we had previously identified as predictive of effectiveness.”

Super Metal Alloys Achieved with Design Tool for Stable Nanocrystals

It has been well understood that if you could decrease the size of the crystals that make up the structures of most metals, you would improve the mechanical properties of those metals, including their strength. However, finding a way to decrease crystal size and maintain that smaller size in the face of heat has proven difficult. Typically, the crystals want to grow larger if exposed to heat or stress.

Now, MIT researchers may have found a way to ensure that the crystals maintain their small size even in the presence of heat and stress, thus achieving the goal of creating stable nanocrystalline materials

The researchers, who have published their work in the journal Science (“Design of Stable Nanocrystalline Alloys”),  came up with a theoretical model for predicting how the mixing of different metals would impact the creation of stable nanostructured alloys.

Heather Murdoch, a graduate student at MIT’s Department of Material Science and Engineering (DMSE), came up with the theoretical model and Tongjai Chookajorn, another graduate student in that department, synthesized the metals to test the stability and properties predicted in Murdoch’s models.

The key to the theoretical model is that it includes considerations of grain boundaries, says Christopher Schuh, head of the material science and engineering department and the two graduate students’ advisor .

“The conventional metallurgical approach to designing an alloy doesn’t think about grain boundaries,” Schuh explains in the MIT press release, adding that typically these models only consider whether two metals can be mixed together.

The first alloy that the researchers came up with was a mixture of tungsten and titanium. It is expected to be unusually strong, which could make it suitable for uses where high-impact considerations are critical, such as industrial equipment shielding or personal armor.

While the alloy the researchers first tested remained stable for a full week at temperatures of 1100 degrees Celsius, it is the possibility of creating entirely new alloys based on the predictive model that has the researchers most excited. “We can calculate, for hundreds of alloys, which ones work, and which don’t,” Murdoch says in the MIT press release.

Julia Weertman, a professor emerita of materials science and engineering at Northwestern University, further notes in the release: “Schuh and his students, using thermodynamic considerations, derived a method to choose alloys that will remain stable at high temperatures. … This research opens up the use of microstructurally stable nanocrystalline alloys in high temperature applications, such as engines for aircraft or power generation.”

Manufactured Nanoparticles Could Pose a Hazard to Crops, But Are They a Risk?

Once again, here come the headlines, across both the trade and mainstream press, warning us that manufactured nanoparticles are a danger to our health and environment. This time it's that nanoparticles stunt soybean crop growth.

The warnings are based on research at the University of California Santa Barbara's Bren School for Environmental Science & Management. The language of the research, however, falls somewhat short of making such unconditional claims.

Instead the research, which was published the Proceedings of the National Academy of Sciences (PNAS),  claims to demonstrate “what could arise over the long term” if plants were grown in soil that had been contaminated with manufactured nanomaterials (MNMs), zinc oxide and cerium oxide.

Even the research that inspired the UC Santa Barbara team to put metal oxides in farming soil only suggested that MNMs “could” alter food crop quality and yield. Of course, if the researchers were to take ordinary household bleach from under the kitchen sink and pour it onto farming soil, they would surely conclude that it "could" alter the quality of the crop.

The real issue—and indeed as with any issue related to chemicals and Environmental, Health and Safety (EHS) concerns—is what is the real risk of these nanoparticles finding themselves in soil concentrations equal to those that were used in the experiments. The relevant formula is Hazard x Exposure = Risk. If we say that MNMs are a hazard, but have no figures on the level of exposure, how are we supposed to determine risk?

In other words, what concentrations of metal oxides did the researchers use in the soil? The answer is not explicit in either the news stories covering the research, nor the abstract that we have access to in the PNAS journal reference. While the researchers do say in at least one of the articles covering the research that “"MNMs…have a high affinity for activated sludge bacteria, and thus concentrate in biosolids," it’s still not clear in what kind of concentrations these nanoparticles exist in the environment, or what that might mean in terms of risk.

In one of the stories covering the research, Patricia Holden, one of the scientists in the research and a professor at the Bren School, has this to say about the risk of these nanoparticles getting into our plant soil: "There could be hotspots, places where you have accumulation, including near manufacturing sites where the materials are being made, or if there are spills."

Could we say then that if you grow your soybeans far from manufacturing sites and far from where there may likely be spills—which is largely the case now, as I understand—that we would mitigate the risk? 

Another troubling aspect of this research is that it has as its "ultimate goal" to help find more environmentally compatible substitutes, according to Holden. Shouldn't the research be to determine if nanoparticles pose a real risk? Instead, that seems to be a given, despite the limited, at best, evidence being provided to prove it.

And what are we substituting in this case? Zinc oxide nanoparticles are found in sunscreens and cosmetics and cerium oxide is used in catalytic converters to reduce carbon monoxide from automobiles. Where is the research to determine how much of these materials are produced, followed by measurements of how much of them are found in random water and soil samples? From there we could determine the key variable of exposure: how much of these nanoparticles in our environment pose a risk. That seems to be an essential line of research if our goal is protecting our environment from substances that are otherwise pretty useful. I am not so sure that setting out to replace them as your ultimate goal really satisfies that aim.

Graphene Is Losing Favor as the Two-Dimensional Material of the Future

 

About 18 months ago, research at Ecole Polytechnique Federale de Lausanne’s (EPFL) Laboratory of Nanoscale Electronics and Structures in Switzerland was beginning to suggest that molybdenum disulfide (MoS2)—which occurs as the mineral molybdenite—may serve as preferable choice over graphene in a post-silicon world. 

Since that time, research has been hotly pursuing the use of this abundant mineral for electronic applications since not only does it possess some of graphene’s attractive qualities, but it brings them to the table with a band gap, unlike graphene. So attractive has this material become that even the discoverers of graphene are now focusing much of their research into using MoS2

Now researchers at MIT, who have struggled to get graphene to do anything in electronics except for some radio-frequency applications, have turned to MoS2 and have quickly managed to get the one-atom-thick material to serve as the basis for a variety of electronic components

The research, which was published this month in the journal Nano Letters ("Integrated Circuits Based on Bilayer MoS2 Transistors"),  produced an inverter, a NAND (Negated AND) gate, a memory device and a ring oscillator using large sheets of the MoS2.

The MIT researchers believe that this list of electronic components is only the beginning of what is possible with the material. One of the researchers, Tomás Palacios, Associate Professor in the Department of Electrical Engineering and Computer Science, believes that the material could find early applications in large-screen displays in which a separate transistor would control each pixel of the display.

Palacios further notes in the MIT press release that the MoS2 when used in combination with other 2-D materials could make light-emitting devices that could be made to make an entire wall glow, making for a warmer and less glaring light that comes from single light bulbs.

This work certainly seems to promise a far greater range of applications for the material than the EPFL research initially indicated. At that time, the Swiss researchers believed the material would probably see use as a complement to graphene in applications that required thin and transparent semiconductors. It seems now the material has much greater promise.

New Form of Carbon Dents Diamonds and More

Nanomaterial science has sometimes resulted in redefining the known forms of carbon. When carbon nanotubes were first discovered over twenty years ago the long-held paradigm of there being just three forms of carbon (diamond, graphite, and amorphous carbon) had to be reassessed. 

Now an international team of researchers working at Argonne National Laboratory's Advanced Photon Source is reporting that they have developed another new form of carbon that is so strong it can dent a diamond.

"We created a new type of carbon material, one that is comparable to diamond in its inability to be compressed," says scientist Lin Wang in an Argonne press release. "Once created under extreme pressures, this material can exist at normal conditions, meaning it could be used for a wide array of practical applications."

The research, which was published in the journal Science ("Long-Range Ordered Carbon Clusters: A Crystalline Material with Amorphous Building Blocks"), combined two forms of carbon—one with an organized structure and another without one—to create a hybrid material that until now had only been theorized about.

The researchers started with carbon-60 “buckyballs”—for which the riddle of their formation was just recently solved--and crushed them with flattened diamond tips. After being crushed, the buckyballs form themselves into a new, harder form of carbon.

The key to the process  is that the crushing had to be done just right with the right amount of pressure. If not done to the correct pressure, the new material would return to its original, less durable buckyball form.

The research also points to this being just the tip of the iceberg in creating new forms of carbon.

Lin Wang further notes in the press release: “The thing that stands out for me from this work is that carbon-60 can crystallize with various solvents, and those solvates would have different periodicities, which enables us to synthesize a series of similar carbon materials with different packing symmetry and carbon cluster size by compressing different types of carbon molecules."

Although it was not discussed in the press release, I couldn’t help but wonder if this new form of carbon will be of interest to the Robert Freitas and Ralph Merkle sect of the molecular nanotechnology community.  Maybe these new carbon materials can serve as the basic building blocks for automated exponential manufacturing where diamonds have not been able to impress even Eric Drexler himself

Entropy Outweighs Gravity in Forming Nanoparticles into Structures

 

Researchers at the University of Michigan have used newly developed computer simulations to demonstrate how one can exploit both the geometry of nanoparticles and the thermodynamic property of entropy to get nanoparticles to organize themselves into structures. 

Physicist and chemical engineering professor Sharon Glotzer and her collaborators in the research, Michael Engel and Pablo Damasceno, recognized—along with others—that nanoparticles with certain geometries have a greater tendency to organize themselves into structures when they were crowded together. From this observation they wondered if nanoparticles with other geometries would do the same.

"We studied 145 different shapes, and that gave us more data than anyone has ever had on these types of potential crystal-formers," Glotzer says in the university press release covering the research. "With so much information, we could begin to see just how many structures are possible from particle shape alone, and look for trends."

The research, which was published in the journal Science (“Predictive Self-Assembly of Polyhedra into Complex Structures”), seems to have revealed some confusion about what entropy is. Even the University of Michigan press release seemed somewhat nonplussed about how a tendency towards “disorder” could create “order.”

It might be better to think of entropy as a tendency toward equilibrium rather than disorder.  This might help better describe how entropy aids the nanoparticles in self-assembling into structures.

To clarify this, Glotzer urges a remake of entropy’s image in the press release. In her explanation, entropy is a measure of possibilities. To describe how this measure of possibilities influences the nanoparticles, Glotzer says to imagine the nanoparticles as a bag of dice being emptied into a jar where there is no gravity. Based on entropy, the dice would find themselves dispersed throughout the jar. However, when you put enough dice into the jar—and they run out of space—they begin to align themselves.

According to the University of Michigan team's simulations, this metaphorical description holds true as well for the nanoparticles. The nanoparticles are so small that the forces of gravity have less of an impact on them than does this property of entropy.

"It's all about options. In this case, ordered arrangements produce the most possibilities, the most options. It's counterintuitive, to be sure," Glotzer says in the release.

What the simulation demonstrated was that by knowing the geometry of the nanoparticles, you can predict the kind of structure they will form.

One of the unresolved mysteries from the simulation the researchers observed is that around 30 percent of the nanoparticles never form into a more complex structure. Why this is the case, they are not sure.

"These may still want to form crystals but got stuck. What's neat is that for any particle that gets stuck, we had other, awfully similar shapes forming crystals," Glotzer said.

IBM Researchers Confirm Decade-Old Theory of Locking Electron Spin Rotation

 

IBM is again taking the lead in spintronics research. Researchers at IBM Zurich and scientists at ETH Zurich for the first time have shown that electrons can be programmed to spin in unison in a semiconductor in what is called a persistent spin helix.

Importantly, the research, which was published in the journal Nature Physics, demonstrated that synchronizing the electrons in this way extends the spin lifetime by 30 times to 1.1 nanoseconds—the same time it takes for an existing 1GHz processor to cycle. It is expected that this level of control over the spin of electrons could result in more energy efficient electronic devices.

In 2003, a theory was proposed that it was possible to lock the spin rotation of electrons. The IBM and ETH Zurich researchers have not only been able to confirm this theory but also demonstrated that electron spins move tens of micrometers in a semiconductor with their orientations synchronously rotating along a path—not unlike a couple dancing a waltz.

In explaining the electron spin with the waltz metaphor, Dr. Gian Salis of the Physics of Nanoscale Systems research group at IBM Zurich said: “If all couples start with the women facing north, after a while the rotating pairs are oriented in different directions. We can now lock the rotation speed of the dancers to the direction they move. This results in a perfect choreography where all the women in a certain area face the same direction. This control and ability to manipulate and observe the spin is an important step in the development of spin-based transistors that are electrically programmable.”

The researchers were able to achieve this feat by first setting up the ability to monitor the spins of the electrons using a time-resolved scanning microscope technique. The researchers were then able to induce the synchronous spin motion by carefully engineering the spin-orbit interaction—a mechanism that couples the spin with the motion of the electron.

While this research promises to bring a greater level of control to spintronics, this research is far from finding its way into our electronic devices any time soon. For example, the experiments performed by the IBM scientists were performed at 40 Kelvin (-233 C, -387 F)—a temperature not suitable for your tablet computer.

Nanotechnology Comes to TedTalks, with Mixed Results

 

For all the TEDTalks that there have been, few have adequately addressed the topic of nanotechnology, with the possible exception of Bill Joy’s ironic path from nanotechnology doomsayer to cheerleader

That is why when I saw that venture capitalist and Nanoholdings CEO Justin Hall-Tipping had been given a forum to discuss nanotechnology for the illustrious TedTalks last year, I had to give a listen (see video below).

Hall-Tipping did not disappoint. As you will see in the video, he provides all the “gee-whiz” nanotech applications one could hope for and throws in some emotion to pull at our heartstrings.

Hall-Tipping highlights three technologies in the video that, as he explains, “exhibit exquisite control over the electron” and could change our current energy paradigm—which, according to his calculations, is doomed to ultimate failure. Two of the technologies come from research originated at the University of Florida; the third comes from the University of Texas at Dallas.

Hall-Tipping says that one of the technologies developed at the University of Florida will result in a world that doesn’t need artificial light to illuminate our nights. In this case, I believe he is referring to the work of Prof. Franky So, developer of lightweight night-vision technologies.  That’s great, but if Hall-Tipping really expects that nearly ubiquitous night-vision capabilities are going to spell the end for artificial light, I think he may have overstated his point.

The other University of Florida technology that Hall-Tipping highlights uses carbon nanotubes embedded in transparent polymer films to absorb the sun’s energy and release it indoors during the winter. And as Hall-Tipping describes it, the same film will “flip it back” in the summer, preventing solar energy from heating living spaces when you want to keep things cool. This application seems to be built around the work of John Reynolds and Andrew Rinzler. I suppose this work could be adapted to collect solar power and reflect away sunlight, but I would like to see some figures on energy conversion efficiency before I start disconnecting myself from the grid.

In the final technology, from the University of Texas at Dallas, nanomaterials (of the carbon nanotube variety, we assume ) enable a device that, according to Hall-Tipping, can “park an electron on the outside, hold it until it's needed, and then to release it and pass it off.” The machine that accomplishes this electron parking, dubbed eBox, has apparently been around since 2009. A prototype has been running for over a year—without, it seems, any effort to commercialize it.

Later in the video, Hall-Tipping makes the cogent point that water shortages are already becoming acute around the world and that energy-intensive desalination is a problematic solution based our current energy paradigm. But removing the grid, or depending on solar power to change the dynamics, seems to be missing the point of a lot of nanotech research related to desalination. I suppose Hall-Tipping’s company is not backing those horses. 

Finally, Hall-Tipping makes his concerns about water shortages personal when he reveals a photograph that he has carried with him for the last 18 years; in it, a young girl in the Sudan is dying of thirst. A truly heart-wrenching image, and as Hall-Tipping says, one that should never happen. But maybe that girl would have been better served by rather simple nanotech-based solutions for providing clean drinking water instead of reinventing the electrical grid.

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Nanoclast

IEEE Spectrum’s nanotechnology blog, featuring news and analysis about the development, applications, and future of science and technology at the nanoscale.

 
Editor
Dexter Johnson
Madrid, Spain
 
Contributor
Rachel Courtland
Associate Editor, IEEE Spectrum
New York, NY
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