The remarkable nanostructure of human bone – Revealed


Interweaving mineral and protein form continuous networks to provide the strength essential for functional bones.

Credit: Dr Roland Kröger

Summary:

Using advanced 3D nanoscale imaging of the mineral in human bone, research teams have shown that the mineral crystals of bone have a hierarchical structure integrated into the larger-scale make-up of the skeleton.

Scientists have produced a 3D nanoscale reconstruction of the mineral structure of bone.

Bone performs equally well whether in an accelerating cheetah or in a heavy elephant, thanks to its toughness and strength.

The properties of bone can be attributed to its hierarchical organisation, where small elements form larger structures.

However, the nanoscale organisation and relationship between bone’s principle components — mineral and protein — have not been fully understood.

Using advanced 3D nanoscale imaging of the mineral in human bone, research teams from the University of York and Imperial College London have shown that the mineral crystals of bone have a hierarchical structure integrated into the larger-scale make-up of the skeleton.

Researchers combined a number of advanced electron microscopy-based techniques, and found that the principal building blocks of mineral at the nanometre scale are curved needle-shaped nanocrystals that form larger twisted platelets that resemble propeller blades.

The blades continuously merge and split throughout the protein phase of bone. The interweaving mineral and protein form continuous networks to provide the strength essential for functional bones.

Lead author, Associate Professor Roland Kröger, from the University of York’s Department of Physics, said: “Bone is an intriguing composite of essentially two materials, the flexible protein collagen and the hard mineral called apatite.”

“There is a lot of discussion about the way these two stiff and flexible phases uniquely combine to provide toughness and strength to bone.

“The combination of the two materials in a hierarchical manner provides bone with mechanical properties that are superior to those of its individual components alone and we find that there are 12 levels of hierarchy in bone.”

Dr Natalie Reznikov, formerly of Imperial College, London and an author on the paper, said: “If we compare this arrangement, for example, to an individual living in a room of a house, this extends to a house in a street, then the street in a neighbourhood, a neighbourhood in a city, a country and on it goes. If you continue to 12 levels you are reaching the size of a galaxy! ”

Professor Molly Stevens, from Imperial College, London, added: “This work builds on the shoulders of many beautiful previous studies investigating the fundamental properties and structure of bone and helps to unlock an important missing piece of the puzzle.”

Besides the large number of nested structures in bone, a common feature of all of them is a slight curvature, providing twisted geometry. To name a few, the mineral crystals are curved, the protein strands (collagen) are braided, the mineralized collagen fibrils twist, and the entire bones themselves have a twist, such as those seen in the curving shape of a rib for example.

Fractals are common in Nature: you can see self-similar patterns in lightning bolts, coast lines, tree branches, clouds and snowflakes. This means that the structure of bone follows a fundamental order principle in Nature.

The authors believe that the fractal-like structure of bone is one of the key reasons for its remarkable attributes.

The findings are published in the journal Science.

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University of Delaware: Programming DNA to deliver cancer drugs


DNA has an important job — it tells your cells which proteins to make. Now, a research team at the University of Delaware has developed technology to program strands of DNA into switches that turn proteins on and off. Credit: University of Delaware

DNA has an important job—it tells your cells which proteins to make. Now, a research team at the University of Delaware has developed technology to program strands of DNA into switches that turn proteins on and off.

UD’s Wilfred Chen Group describes their results in a paper published Monday, March 12 in the journal Nature Chemistry. This technology could lead to the development of new cancer therapies and other drugs.

Computing with DNA

This project taps into an emerging field known as DNA computing. Data we commonly send and receive in everyday life, such as text messages and photos, utilize binary code, which has two components—ones and zeroes. DNA is essentially a code with four components, the nucleotides guanine, adenine, cytosine, and thymine. In cells, the arrangement of these four nucleotides determines the output—the proteins made by the DNA. Here, scientists have repurposed the DNA code to design logic-gated DNA circuits.

“Once we had designed the system, we had to first go into the lab and attach these DNA strands to various proteins we wanted to be able to control,” said study author Rebecca P. Chen, a doctoral student in chemical and biomolecular engineering (no relation to Wilfred Chen).

The custom sequence designed DNA strands were ordered from a manufacturer while the proteins were made and purified in the lab. Next, the protein was attached to the DNA to make protein-DNA conjugates.

The group then tested the DNA circuits on E. coli bacteria and human cells. The target proteins organized, assembled, and disassembled in accordance with their design.

“Previous work has shown how powerful DNA nanotechnology might possibly be, and we know how powerful proteins are within cells,” said Rebecca P. Chen. “We managed to link those two together.”

Applications to drug delivery

The team also demonstrated that their DNA-logic devices could activate a non-toxic cancer prodrug, 5-fluorocytosine, into its toxic chemotherapeutic form, 5-fluorouracil. Cancer prodrugs are inactive until they are metabolized into their therapeutic form.

In this case, the scientists designed DNA circuits that controlled the activity of a protein that was responsible for conversion of the prodrug into its active form. The DNA circuit and protein activity was turned “on” by specific RNA/DNA sequence inputs, while in the absence of said inputs the system stayed “off.”

To do this, the scientists based their sequence inputs on microRNA, small RNA molecules that regulate cellular gene expression. MicroRNA in cancer cells contains anomalies that would not be found in healthy cells. For example, certain microRNA are present in cancer cells but absent in healthy cells. The group calculated how nucleotides should be arranged to activate the cancer prodrug in the presence of cancer microRNA, but stay inactive and non-toxic in a non-cancerous environment where the microRNA are missing.

When the cancer microRNAs were present and able to turn the DNA circuit on, cells were unable to grow. When the circuit was turned off, cells grew normally.

Wilfred Chen (left) and Rebecca P. Chen are developing new biomolecular tools to address key global health problems. Credit: University of Delaware/ Evan Krape

This technology could have wide applications not only to other diseases besides cancer, but also beyond the biomedical field. For example, the research team demonstrated that their technology could be applied to the production of biofuels, by utilizing their technology to guide an enzymatic cascade, a series of chemical reactions, to break down a plant fiber.

Using the newly developed technology, researchers could target any DNA sequence of their choosing and attach and control any protein they want. Someday, researchers could “plug and play” programmed DNA into a variety of cells to address a variety of diseases, said study author Wilfred Chen, Gore Professor of Chemical Engineering.

“This is based on a very simple concept, a logical combination, but we are the first to make it work,” he said. “It can address a wide scope of problems, and that makes it very intriguing.”

More information: Rebecca P. Chen et al, Dynamic protein assembly by programmable DNA strand displacement, Nature Chemistry (2018). DOI: 10.1038/s41557-018-0016-9

Provided by: University of Delaware

Is It Possible? Will You Soon be Able to Replace Your Glasses And Contacts With Nanoparticle Eyedrops?


A revolutionary, cutting-edge technology, developed by researchers at Bar-Ilan University’s Institute of Nanotechnology and Advanced Materials (BINA), has the potential to provide a new alternative to eyeglasses, contact lenses, and laser correction for refractive errors.

The technology, known as Nano-Drops, was developed by Dr. David Smadja (Ophthalmologist from Shaare Zedek Medical Center), Prof. Zeev Zalevsky, from Bar-Ilan’s Kofkin Faculty of Engineering, and Prof. Jean-Paul Moshe Lellouche, Head of the Department of Chemistry at Bar-Ilan. A related patent on this new invention was recently filed by Birad – Research & Development Company Ltd., the commercializing company of Bar-Ilan University.

Nano-Drops achieve their optical effect and correction by locally modifying the corneal refractive index. The magnitude and nature of the optical correction is adjusted by an optical pattern that is stamped onto the superficial layer of the corneal epithelium with a laser source. The shape of the optical pattern can be adjusted for correction of myopia (nearsightedness), hyperopia (farsightedness) or presbyopia (loss of accommodation ability). The laser stamping onto the cornea takes a few milliseconds and enables the nanoparticles to enhance and ‘activate’ this optical pattern by locally changing the refractive index and ultimately modifying the trajectory of light passing through the cornea.

The laser stamping source does not relate to the commonly known ‘laser treatment for visual correction’ that ablates corneal tissue. It is rather a small laser device that can connect to a smartphone and stamp the optical pattern onto the corneal epithelium by placing numerous adjacent pulses in a very speedy and painless fashion.  Tiny corneal spots created by the laser allow synthetic and biocompatible nanoparticles to enter and locally modify the optical power of the eye at the desired correction.

In the future this technology may enable patients to have their vision corrected in the comfort of their own home. To accomplish this, they would open an application on their smartphone to measure their vision, connect the laser source device for stamping the optical pattern at the desired correction, and then apply the Nano-Drops to activate the pattern and provide the desired correction.

Upcoming in-vivo experiments in rabbits will allow the researchers to determine how long the effect of the Nano-Drops will last after the initial application. Meanwhile, this promising technology has been shown, through ex-vivo experiments, to efficiently correct nearly 3 diopters of both myopia and presbyopia in pig eyes.

Bar-Ilan University, founded in 1955, was one of the first comprehensive research universities to be established in Israel.  From 70 students to 17,000, its milestone achievements in the sciences and humanities have made an indelible imprint on the landscape of the nation.  The university has 8 faculties, four of which focus on STEM research. They include Medicine, Exact Sciences (Physics, Chemistry, Computer Science, Biophysics and Mathematics), Life Sciences and Engineering.

Bar-Ilan University

New nanoparticle may aid cancer detection


Cellular Messenger Cornell 9-scientistsdiAn intricate pattern – a molecular model of the influenza virus. The influenza virion (as the infectious particle is called) is roughly spherical. It is an enveloped virus – that is, the outer layer is a lipid membrane which is taken from the host cell in which the virus multiplies. 

A new nanoparticle, at the cellular level, may reveal how cancer cells move to different locations in the human body. This process involves co-opting the human body’s inter-cellular delivery service.

The insight into the cellular messenger system comes from Weill Cornell Medicine scientists. The discovery is of importance since it could help medical scientists to understand how cancer cells can spread to various other locations.

 

With the research, the medics have used a novel technique called asymmetric flow field-flow fractionation. Through this the researchers were able to shift and sort a particular type of nano-sized particles termed exosomes. These particles are secreted by cancer cells and they are formed of DNA, RNA, fats and proteins.

 

Exosomes are cell-derived vesicles that are present in many cell fluids, including blood, and urine; they provide a means of intercellular communication and of transmission of macromolecules between cells. In medicine exosomes can potentially be used for prognosis, for therapy, and as biomarkers for health and disease.

 

By using the asymmetric flow field-flow fractionation, the scientists were able to separate out two distinct exosome subtypes. This has led to the discovery of the new type of nanoparticle. Asymmetrical flow field flow fractionation is a common and state-of-the art method for fractionation and separation of macromolecules and particles in a suspension.

 

Metastatic breast cancer in pleural fluid.

Metastatic breast cancer in pleural fluid. euthman/flickr

 

Discussing the research with Controlled Environments magazine, lead researcher Dr. David Lyden explains further: We found that exomeres are the most predominant particle secreted by cancer cells. They are smaller and structurally and functionally distinct from exosomes. Exomeres largely fuse with cells in the bone marrow and liver, where they can alter immune function and metabolism of drugs.”

 

The researcher adds: “The latter finding may explain why many cancer patients are unable to tolerate even small doses of chemotherapy due to toxicity.”

 

Importantly exosomes and exomeres have different biophysical characteristics, like stiffness and electric charge. With this, the findings show, the more rigid the particle, the easier it is likely taken up by cells, rendering exomeres more effective messengers of transferring tumor information to recipient cells.

 

The research further shows how exosomes and exomeres differ in relation to their influence in triggering cancer. Exomeres can carry metabolic enzymes to the liver. Here exomeres are able to cause the liver to “reprogram” its metabolic function and trigger tumor progression.

 

The researchers plan to patent the new technology and develop a diagnostic tool to assist with cancer detection. This will help medics to understand how cancers grow and spread to other organs.

 

The research has been published in the journal Nature Cell Biology. The research paper is titled “Identification of distinct nanoparticles and subsets of extracellular vesicles by asymmetric flow field-flow fractionation.”

 

In related news, Digital Journal has previously reported that researchers have used nanotechnology to improve drug delivery. This is in the form of tailorable nanoscale emulsions which effectively interact with their intended targets (see: “Delivering drugs via nanoscale emulsion.”)

 

Essential Science

 

Demonstrating the need for good cleaning and disinfection using ultraviolet light to show how easy i...

Demonstrating the need for good cleaning and disinfection using ultraviolet light to show how easy it is to miss parts of a surface when cleaning. Tim Sandle

 

This article is part of Digital Journal’s regular Essential Science columns. Each week Tim Sandle explores a topical and important scientific issue. Last week the association between household cleaning chemicals and respiratory problems was examined in light of a new study from the University of Bergen in Norway, which raises concerns about the longer-term health impact.

 

The week before the topic of nanotechnology and the development of a new generation of antimalarial drugs was discussed.

“On the Rebound” The quest to introduce self-healing behaviors in Nanoparticles: Stanford University


In a newly discovered twist, Argonne scientists and collaborators found that palladium nanoparticles can repair atomic dislocations in their crystal structure. This self-healing behavior could be worth exploring in other materials. (Image by Argonne National Laboratory.)

Our bodies have a remarkable ability to heal from broken ankles or dislocated wrists. Now, a new study has shown that some nanoparticles can also “self-heal” after experiencing intense strain, once that strain is removed.

New research from the U.S. Department of Energy’s (DOE) Argonne National Laboratory and Stanford University has found that palladium nanoparticles can repair atomic dislocations in their crystal structure. This newly discovered twist could ultimately advance the quest to introduce self-healing behaviors in other materials.

“It turns out that these nanoparticles function much more like the human body healing from an injury than like a broken machine that can’t fix itself.” – Andrew Ulvestad, Argonne materials scientist

The research follows a study from last year, in which Argonne researchers looked at the sponge-like way that palladium nanoparticles absorb hydrogen.

When palladium particles absorb hydrogen, their spongy surfaces swell. However, the interiors of the palladium particles remain less flexible. As the process continues, something eventually cracks in a particle’s crystal structure, dislocating one or more atoms.

“One would never expect the dislocation to come out under normal conditions,” said Argonne materials scientist Andrew Ulvestad, the lead author of the study. “But it turns out that these nanoparticles function much more like the human body healing from an injury than like a broken machine that can’t fix itself.”

Ulvestad explained that the dislocations form as a way for the material to relieve the stress placed on its atoms by the infusion of additional hydrogen. When scientists remove the hydrogen from the nanoparticle, the dislocations have room to mend.

Using the X-rays provided by Argonne’s Advanced Photon Source, a DOE Office of Science User Facility, Ulvestad was able to track the motion of the dislocations before and after the healing process. To do so, he used a technique called Bragg coherent diffraction imaging, which identifies a dislocation by the ripple effects it produces in the rest of the particle’s crystal lattice.

In some particles, the stress of the hydrogen absorption introduced multiple dislocations. But even particles that dislocated in multiple places could heal to the point where they were almost pristine.

“In some cases, we saw five to eight original dislocations, and some of those were deep in the particle,” Ulvestad said. “After the particle healed, there would be maybe one or two close to the surface.”

Although Ulvestad said that researchers are still unsure exactly how the material heals, it likely involves the relationship between the material’s surface and its interior, he explained.

By better understanding how the material heals, Ulvestad and his colleagues hope to tailor the dislocations to improve material properties. “Dislocations aren’t necessarily bad, but we want to control how they form and how they can be removed,” he said.

The study, entitled “The self-healing of defects induced by the hydriding phase transformation in palladium nanoparticles,” appeared November 9 in Nature Communications.

The work was supported by DOE’s Office of Science and the National Science Foundation.

Argonne National Laboratory seeks solutions to pressing national problems in science and technology. The nation’s first national laboratory, Argonne conducts leading-edge basic and applied scientific research in virtually every scientific discipline. Argonne researchers work closely with researchers from hundreds of companies, universities, and federal, state and municipal agencies to help them solve their specific problems, advance America’s scientific leadership and prepare the nation for a better future. With employees from more than 60 nations, Argonne is managed by UChicago Argonne, LLC for the U.S. Department of Energy’s Office of Science.

The U.S. Department of Energy’s Office of Science is the single largest supporter of basic research in the physical sciences in the United States and is working to address some of the most pressing challenges of our time. For more information, visit the Office of Science website.

Rice University (NEWT) / China team use phage-enhanced nanoparticles to kill bacteria that foul water treatment systems


Clusters of nanoparticles with phage viruses attached find and kill Escherichia coli bacteria in a lab test at Rice University. 

Abstract:
Magnetic nanoparticle clusters have the power to punch through biofilms to reach bacteria that can foul water treatment systems, according to scientists at Rice University and the University of Science and Technology of China.
Magnetized viruses attack harmful bacteria: Rice, China team uses phage-enhanced nanoparticles to kill bacteria that foul water treatment systems.

Researchers at Rice and the University of Science and Technology of China have developed a combination of antibacterial phages and magnetic nanoparticle clusters that infect and destroy bacteria that are usually protected by biofilms in water treatment systems. (Credit: Alvarez Group/Rice University)

The nanoclusters developed through Rice’s Nanotechnology-Enabled Water Treatment (NEWT) Engineering Research Center carry bacteriophages – viruses that infect and propagate in bacteria – and deliver them to targets that generally resist chemical disinfection.

Without the pull of a magnetic host, these “phages” disperse in solution, largely fail to penetrate biofilms and allow bacteria to grow in solution and even corrode metal, a costly problem for water distribution systems.

The Rice lab of environmental engineer Pedro Alvarez and colleagues in China developed and tested clusters that immobilize the phages. A weak magnetic field draws them into biofilms to their targets.

The research is detailed in the Royal Society of Chemistry’s Environmental Science: Nano.
“This novel approach, which arises from the convergence of nanotechnology and virology, has a great potential to treat difficult-to-eradicate biofilms in an effective manner that does not generate harmful disinfection byproducts,” Alvarez said.

Biofilms can be beneficial in some wastewater treatment or industrial fermentation reactors owing to their enhanced reaction rates and resistance to exogenous stresses, said Rice graduate student and co-lead author Pingfeng Yu. “However, biofilms can be very harmful in water distribution and storage systems since they can shelter pathogenic microorganisms that pose significant public health concerns and may also contribute to corrosion and associated economic losses,” he said.

The lab used phages that are polyvalent – able to attack more than one type of bacteria – to target lab-grown films that contained strains of Escherichia coli associated with infectious diseases and Pseudomonas aeruginosa, which is prone to antibiotic resistance.

The phages were combined with nanoclusters of carbon, sulfur and iron oxide that were further modified with amino groups. The amino coating prompted the phages to bond with the clusters head-first, which left their infectious tails exposed and able to infect bacteria.

The researchers used a relatively weak magnetic field to push the nanoclusters into the film and disrupt it. Images showed they effectively killed E. coli and P. aeruginosa over around 90 percent of the film in a test 96-well plate versus less than 40 percent in a plate with phages alone.

The researchers noted bacteria may still develop resistance to phages, but the ability to quickly disrupt biofilms would make that more difficult. Alvarez said the lab is working on phage “cocktails” that would combine multiple types of phages and/or antibiotics with the particles to inhibit resistance.

Graduate student Ling-Li Li of the University of Science and Technology of China, Hefei, is co-lead author of the paper. Co-authors are graduate student Sheng-Song Yu and Han-Qing Yu, a professor at the University of Science and Technology of China, and graduate student Xifan Wang and temporary research scientist Jacques Mathieu of Rice.


The National Science Foundation and its Rice-based NEWT Engineering Research Center supported the research.

MIT: Key flow mechanisms, crucial to carbon sequestration, Oil recovery and fuel-cell operation, have been visualized.


MIT-Multiphase-Flow_0 Wetability 082616

Lab experiments carried out by an MIT and Oxford University team provide detailed information about how a liquid moves through spaces in a porous material, revealing the key role of a characteristic called wettability.

Courtesy of the researchers

One of the most promising approaches to curbing the flow of human-made greenhouse gases into the atmosphere is to capture these gases at major sources, such as fossil-fuel-burning power plants, and then inject them into deep, water-saturated rocks where they can remain stably trapped for centuries or millennia.

This is just one example of fluid-fluid displacement in a porous material, which also applies to a wide variety of natural and industrial processes — for example, when rainwater penetrates into soil by displacing air, or when oil recovery is enhanced by displacing the oil with injected water.

Now, a new set of detailed lab experiments has provided fresh insight into the physics of this phenomenon, under an unprecedented range of conditions. These results should help researchers understand what happens when carbon dioxide flows through deep saltwater reservoirs, and could shed light on similar interactions such as those inside fuel cells being used to produce electricity without burning hydrocarbons.

The new findings are being published this week in the journal PNAS, in a paper by Ruben Juanes, MIT’s ARCO Associate Professor in Energy Studies; Benzhong Zhao, an MIT graduate student; and Chris MacMinn, an associate professor at Oxford University.

A crucial aspect of fluid-fluid displacement is the displacement efficiency, which measures how much of the pre-existing fluid can be pushed out of the pore space. High displacement efficiency means that most of the pre-existing fluid is pushed out, which is usually a good thing — with oil recovery, for example, it means that more oil would be captured and less would be left behind. Unfortunately, displacement efficiency has been very difficult to predict.

A key factor in determining displacement efficiency, Juanes says, is a characteristic called wettability. Wettability is a material property that measures a preference by the solid to be in contact with one of the fluids more than the other. The team found that the stronger the preference for the injected fluid, the more effective the displacement of the pre-existing fluid from the pores of the material — up to a point. But if the preference for the injected fluid increases beyond that optimal point, the trend reverses, and the displacement becomes much less efficient. The discovery of the existence of this ideal degree of wettability is one of the significant findings of the new research.

The work was partly motivated by recent advances in scanning techniques that make it possible to “directly characterize the wettability of real reservoir rocks under in-situ conditions,” says Zhao. But just being able to characterize the wettability was not sufficient, he explains. The key question was “Do we understand the physics of fluid-fluid displacement in a porous medium under different wettability conditions?” And now, after their detailed analysis, “We do have a fundamental understanding” of the process, Zhao says. MacMinn adds that “it comes from the design of a novel system that really allowed us to look in detail at what is happening at the pore scale, and in three dimensions.”

This GIF shows the way fluid distribution through pore spaces varies under different injection rates of water. The colors show the degree of saturation of the invading water. At low rates (left), the water advances in rapid bursts followed by quiet periods. At intermediate rates (center), the invading fluid advances by sequentially coating the walls of posts used to simulate pores in the team’s microfluidic cell. At high rates (right), the water advances in thin films along the solid surfaces.

 

 

 

 

 

 

 

In order to clearly define the physics behind these flows, the researchers did a series of lab experiments in which they used different porous materials with a wide range of wetting characteristics, and studied how the flows varied.

In natural environments such as aquifers or oil reservoirs, the wettability of the material is predetermined. But even so, Juanes says, “there are ways you can modify the wettability in the field,” such as by adding specific chemical compounds like surfactants (similar to soap) to the injected fluid.

By making it possible to understand just what degree of wettability is desirable for a particular situation, the new findings “in principle, could be very advantageous” for designing carbon sequestration or enhanced oil recovery schemes for a specific geological setting.

The same principles apply to some polymer electrolyte fuel cells, where water vapor condenses at the fuel cell’s cathode and has to migrate through a porous membrane. Depending on the exact mix of gas and liquid, these flows can be detrimental to the performance of the fuel cell, so controlling and predicting the way these flows work can be important in designing such cells.

In addition, the same process of liquid and gas interacting in pore spaces also applies to the way freshwater aquifers get recharged by rainfall, as the water percolates into the ground and displaces air in the soil. A better understanding of this process could be important for management of ever-scarcer water resources, the team says.

“This is a very interesting study of pore-scale multiphase fluid flow in two-dimensional micromodels,” says David Weitz, a professor of physics and applied physics at Harvard University, who was not involved in this work. “The advantage of this work is that the authors look in more detail at the mechanisms of wetting and displacement of the fluid in the pores,” he says. “This is a very important aspect of fluid flow in porous media.”

This research was supported by the U.S. Department of Energy and the MIT Energy Initiative.

Update: MIT; UC San Diego; Harvard Universities: Energy-carrying particles called ‘topological plexcitons’ could make possible the design of ‘next generation’ solar cells and miniaturized optical circuitry


Plexcitons 060916 11-scientistsde

Plexcitons travel for 20,000 nanometers, a length which is on the order of the width of human hair. Credit: Joel Yuen-Zhou

Scientists at UC San Diego, MIT and Harvard University have engineered “topological plexcitons,” energy-carrying particles that could help make possible the design of new kinds of solar cells and miniaturized optical circuitry.

The researchers report their advance in an article published in the current issue of Nature Communications.

Within the Lilliputian world of physics, light and matter interact in strange ways, exchanging energy back and forth between them.

plexciton-plasmonexciton-coupling-1 II 060916 -638

“When light and matter interact, they exchange energy,” explained Joel Yuen-Zhou, an assistant professor of chemistry and biochemistry at UC San Diego and the first author of the paper. “Energy can flow back and forth between light in a metal (so called plasmon) and light in a molecule (so called exciton). When this exchange is much faster than their respective decay rates, their individual identities are lost, and it is more accurate to think about them as hybrid particles; excitons and plasmons marry to form plexcitons.” mit_logo

Materials scientists have been looking for ways to enhance a process known as exciton energy transfer, or EET, to create better as well as miniaturized photonic circuits which are dozens of times smaller than their silicon counterparts.

“Understanding the fundamental mechanisms of EET enhancement would alter the way we think about designing solar cells or the ways in which energy can be transported in nanoscale materials,” said Yuen-Zhou.

The drawback with EET, however, is that this form of energy transfer is extremely short-ranged, on the scale of only 10 nanometers, and quickly dissipates as the excitons interact with different molecules.

plexciton-plasmonexciton-coupling-13-638One solution to avoid those shortcomings is to hybridize excitons in a molecular crystal with the collective excitations within metals to produce plexcitons, which travel for 20,000 nanometers, a length which is on the order of the width of human hair.

Plexcitons are expected to become an integral part of the next generation of nanophotonic circuitry, light-harvesting solar energy architectures and chemical catalysis devices. But the main problem with plexcitons, said Yuen-Zhou, is that their movement along all directions, which makes it hard to properly harness in a material or device.

He and a team of physicists and engineers at MIT and Harvard found a solution to that problem by engineering particles called “topological plexcitons,” based on the concepts in which solid state physicists have been able to develop materials called “topological insulators.”

“Topological insulators are materials that are perfect electrical insulators in the bulk but at their edges behave as perfect one-dimensional metallic cables,” Yuen-Zhou said. “The exciting feature of is that even when the material is imperfect and has impurities, there is a large threshold of operation where electrons that start travelling along one direction cannot bounce back, making electron transport robust. In other words, one may think about the electrons being blind to impurities.”

Plexcitons, as opposed to electrons, do not have an electrical charge. Yet, as Yuen-Zhou and his colleagues discovered, they still inherit these robust directional properties. Adding this “topological” feature to plexcitons gives rise to directionality of EET, a feature researchers had not previously conceived. This should eventually enable engineers to create plexcitonic switches to distribute selectively across different components of a new kind of solar cell or light-harvesting device.

Explore further: Topological insulators could exist in six new types not seen before, theorists predict

More information: Nature Communications, DOI: 10.1038/NCOMMS11783

 

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Tiny packages may pack powerful treatment for brain tumors: Nanocarrier provides efficient delivery of chemotherapeutic drug


Brain Tumor 052416 160521071206_1_540x360Dr. Ann-Marie Broome, right, likes collaborating with Dr. Amy Lee Bredlau, left, who brings a clincial perspective to the laboratory.
Credit: Sarah Pack

Medical University of South Carolina: Great discoveries do come in small packages. Few know that better than Ann-Marie Broome, Ph.D., who feels nanotechnology holds the future of medicine with its ability to deliver powerful drugs in tiny, designer packages.

Her latest research finds the perfect application — targeting cancerous brain tumor cells.

Results from her recent paper published online in the international journal Nanomedicine — Future Medicine found that a lipid nanocarrier engineered to be small enough to get past the blood-brain barrier could be targeted to deliver a chemotherapeutic drug more efficiently to tumor cells in the brain. In vivo studies showed specific uptake and increased killing in glial cells, so much so that Broome initially questioned the results.

“I was very surprised by how efficiently and well it worked once we got the nanocarrier to those cells,” she said, explaining that initial results were so promising that she had her team keep repeating the experiments, using different cell lines, dosage amounts and treatment times.Researchers and clinicians are excited because it potentially points the way to a new treatment option for patients with certain conditions, such as glioblastoma multiforme (GBM), the focus of this study.

Glioblastoma multiforme is a devastating disease with no curative options due to several challenges, said Broome, who is the director of Molecular Imaging of the Medical University of South Carolina’s Center for Biomedical Imaging and director of Small Animal Imaging of Hollings Cancer Center. The brain tumor has a significant overall mortality, in part due to its location, difficulty of surgical treatment and the inability to get drugs through the blood-brain barrier, a protective barrier designed to keep a stable environment within and surrounding the brain.

In 40 percent of cases, standard treatments will extend life expectancy 4 to 7 months. “It’s really a dismal outcome. There are better ways to deliver standard of care.”

That’s where Broome and her nanotechnology lab enter in.

Nanotechnology is medicine, engineering, chemistry, and biology all bundled together and conducted at the nanoscale, between the range of 1 to 1,000 nanometers. For comparison, a thin newspaper page is about 100,000 nanometers thick. Broome and her team took what they know about the cancer’s biology and of platelet-derived growth factor (PDGF), one of numerous growth factor proteins that regulates cell growth and division and is also overexpressed on tumor cells in the brain. With that in mind, they engineered a micelle that is a phospholipid nanocarrier, “a bit of fat globule,” to deliver a concentrated dose of the chemotherapy drug temozolomide (TMZ) to the GBM tumor cells.

“Micelles of a certain size will cross the blood-brain barrier carrying a concentrated amount of TMZ,” she explained about how the nanotechnology works. “The PDGF is used much like a postal address. The micelle gets it to the street, and the PDGF gets it to the house.” This targeting ability is important because researchers have learned that it’s likely that the GBM will recur, she said.

“It’s thought that satellite cells left behind after surgical removal are the fastest growing and most dangerous ones. We’re trying to kill those rapidly growing satellite cells that will grow into new tumors in that location or others. These satellite tumors grow more aggressively than others. You have to hit them hard, fast and aggressively.”

Surprisingly, nanotechnology is already a part of everyday life in many ways that people don’t realize. It’s used in everything from makeup as moisturizers or UV sunscreens to ice cream to maintain frozen temperatures and creamy textures.

In medicine, Broome said, researchers construct nanocarriers that are stable and stealthy. “Your immune cells can’t attack them. They remain hidden.”When the package gets to where it’s going, nanotechnologists have various methods to get the micelles to release their payloads- one way is to use the acidic nature of a rapidly growing tumor. In normal circulation, the pH of blood is slightly alkaline and the micelle stays intact. What researchers have discovered is that in many tumor types, the pH drastically changes to an acidic environment.

“While the tumor is growing, it creates waste by-products and metabolites that alter the pH, thus lowering it. As the center becomes more necrotic, it becomes even more acidic.”

The change in pH triggers a release of the drug from our micelles just where clinicians want it to go to reduce toxicity to the rest of the body, she said.

“We take advantage of the tumor’s natural environment as well as the cellular expression. I’m a big proponent of understanding that microenvironment has an impact on how well you can treat tumors. It’s probably why so many therapeutics fail — because you have to take into account the immune system, the local environment, and the cells themselves — all three of these are important considerations.”

That’s why nanotechnology has an edge in shaping future cancer treatments.

“It’s very important that the public recognize that nanotechnology is the future. It impacts so many different fields. It has a clear impact on cancer biology and potentially has an impact on cancers that are inaccessible, untreatable, undruggable — that in normal circumstances are ultimately a death knell.”All too familiar with this is researcher and clinician Amy Lee Bredlau, M.D., director of MUSC Health’s Pediatric Brain Tumor Program, who also was a part of the study. Broome said she relishes having a clinician’s perspective in the lab to focus the group on translational outcomes for the patients.

“That’s why it’s so gratifying working with Amy Lee. She works with many cancers for which there are no options. We’re trying to provide options.”

Bredlau agreed. “This paper is exciting because it demonstrates a novel approach to treating brain tumors, combining nanotechnology targeting to a marker of brain tumors with a specialized delivery system. It will allow us eventually to target aggressive childhood and adult brain tumors.”

Bredlau said she’s taking time out from her clinical practice to be in Broome’s research lab because she knows that’s how she can best accelerate the process.

“I am passionate about improving the lives of my patients, now and in the future. Advancing research now is the best way to improve the lives of my patients to come.”

Bredlau sees nanotechnology as having the power to revolutionize treatment for brain tumors. “When we perfect this strategy, we will be able to deliver potent chemotherapies only to the area that needs them. This will dramatically improve our cure rates while cutting out a huge portion of our side effects from chemotherapy. Imagine a world where a cancer diagnosis not only was not life-threatening, but also did not mean that you would be tired, nauseated or lose your hair.”

Though excited by the study’s results, Broome cautions that there’s much more work to be done before new treatment options are readily available for patients.

“It may or may not be effective for all types of GBMs. There are subtypes as well as therapeutic-resistant GBMs that these nanocarriers may not impact. We need to continue rigorous testing to verify and validate our initial findings.”

They will be exploring an expanding field of targeted biomarkers available for GBM tumor cells. As is common in breast cancer and other cancer types, this cancer has specific cell surface receptors that are overexpressed, she said.

And though the drug TMZ in this protocol works very efficiently, it may not be the best drug for the majority of the people, she said. “Now that we know we can get the drug to its designated location and get it to work efficiently, we have a comparator. We can test more lethal and different combinations of drugs that have never before been used in this scenario.”

This method of drug delivery also opens new windows to immunotherapy treatments garnering recognition internationally. Broome wants to take chemotherapeutics and combine them with new immuno-therapeutic treatments to form unique combination delivery packages.

It’s ambitious.

Broome, whose team jokes that she keeps “a long, running list of impossible tasks,” said the work also translates to so many fields beyond cancer including stroke, transplant and regenerative medicine, where it could be used for example in wound healing in dermatology or organ maintenance in transplantation. It’s one reason she submitted her latest research to an international journal because she wants to accelerate advances in nanotechnology, a field she has no doubt will change how medicine is done.

“They are the primary reason I continue to do what I do,” she said of the patients who face grim diagnoses. “They give me hope. The possibilities for nanotherapeutics are endless and bright.”


Story Source:

The above post is reprinted from materials provided by Medical University of South Carolina. The original item was written by Dawn Brazell. Note: Materials may be edited for content and length.


Journal Reference:

  1. Kayla Miller, Suraj Dixit, Amy-Lee Bredlau, Alfred Moore, Emilie McKinnon, Ann-Marie Broome. Delivery of a drug cache to glioma cells overexpressing platelet-derived growth factor receptor using lipid nanocarriers.Nanomedicine, 2016; 11 (6): 581 DOI: 10.2217/nnm.15.218

Rice University: Microwaved “Nanoribbons” may bolster oil and gas wells


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Rice University researchers have developed a method to treat composite materials of graphene nanoribbons and thermoset polymers with microwaves in a way that could dramatically reinforce wellbores for oil and gas production. Credit: Nam Dong Kim/Rice University

 

Wellbores drilled to extract oil and gas can be dramatically reinforced with a small amount of modified graphene nanoribbons added to a polymer and microwaved, according to Rice University researchers.

The Rice labs of chemist James Tour and civil and environmental engineer Rouzbeh Shahsavari combined the nanoribbons with an oil-based thermoset intended to make wells more stable and cut production costs. When cured in place with low-power microwaves emanating from the drill assembly, the composite would plug the microscopic fractures that allow drilling fluid to seep through and destabilize the walls.

Results of their study appeared in the American Chemical Society journal ACS Applied Materials and Interfaces.

The researchers said that in the past, drillers have tried to plug fractures with mica, calcium carbonate, gilsonite and asphalt to little avail because the particles are too large and the method is not efficient enough to stabilize the wellbore.

In lab tests, a polymer-nanoribbon mixture was placed on a sandstone block, similar to the rock that is encountered in many wells. The team found that rapidly heating the to more than 200 degrees Celsius with a 30-watt microwave was enough to cause crosslinking in the polymer that had infiltrated the sandstone, Tour said. The needed is just a fraction of that typically used by a kitchen appliance, he said.

“This is a far more practical and cost-effective way to increase the stability of a well over a long period,” Tour said.

In the lab, the nanoribbons were functionalized—or modified—with polypropylene oxide to aid their dispersal in the polymer. Mechanical tests on composite-reinforced sandstone showed the process increased its average strength from 5.8 to 13.3 megapascals, a 130 percent boost in this measurement of internal pressure, Shahsavari said. Similarly, the toughness of the composite increased by a factor of six.

“That indicates the composite can absorb about six times more energy before failure,” he said. “Mechanical testing at smaller scales via nanoindentation exhibited even more local enhancement, mainly due to the strong interaction between nanoribbons and the polymer. This, combined with the filling effect of the nanoribbon-polymer into the pore spaces of the sandstone, led to the observed enhancements.”

The researchers suggested a low-power microwave attachment on the drill head would allow for in-well curing of the nanoribbon-polymer solution.

Explore further: Graphene nanoribbons grow due to domino-like effect

More information: Nam Dong Kim et al, Microwave Heating of Functionalized Graphene Nanoribbons in Thermoset Polymers for Wellbore Reinforcement, ACS Applied Materials & Interfaces (2016). DOI: 10.1021/acsami.6b01756

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