Researchers from Brown University and the University of Rhode Island have demonstrated a promising new way to increase the effectiveness of radiation in killing cancer cells. The approach involves gold nanoparticles tethered to acid-seeking compounds called pHLIPs. The pHLIPs (pH low-insertion peptides) home in on high acidity of malignant cells, delivering their nanoparticle passengers straight to the cells' doorsteps. The nanoparticles then act as tiny antennas, focusing the energy of radiation in the area directly around the cancer cells. In a paper published in the ("Enhancement of radiation effect on cancer cells by gold-pHLIP"), the research team shows that the approach substantially increases the cancer-killing power of radiation in lab tests. 
Cancer-seeking peptides — pHLIPs — find acidic tumor cells. By attaching gold nanoparticles to pHLIPs, cancer cells receive “antennas” for radiation therapy. Cancer cells (A) treated with gold alone (dark areas) take up far less gold than cells with gold delivered by pHLIPs (B). C and D are cellular close-up with pHLIP-delivered gold. (Images: Reshetnyak and Andreev/URI) "This study was a good proof of concept," said Michael Antosh, assistant professor (research) in Brown's Institute for Brain and Neural Systems and the paper's lead author. "We're encouraged by our initial results and we're excited to take the next step and test this in mice." The team is hopeful that the approach could ultimately improve radiation treatment for cancer patients. By increasing the effectiveness that a given dose of radiation has on cancer, the technique could reduce the overall radiation dose a patient requires, which would in turn reduce side effects. It could also increase the effectiveness of radiation at doses currently administered. Special delivery This research is an extension of work started by Yana Reshetnyak and Oleg Andreev, professors in the URI's Division of Biological and Medical Physics, and professor Donald Engelman of Yale University, the inventors of pHLIP technology. The URI/Yale team had previously developed pHLIPs as a potential delivery system for cancer drugs and diagnostic agents. Cancer cells are generally more acidic than healthy cells, and pHLIPs are natural acid-seekers. "We previously demonstrated that pHLIP-nanogold particles could find and accumulate in tumors established in mice," Reshetnyak said. "Now our task is to test if we can treat cancer by irradiating tumors with nanogold particles more efficiently in comparison with traditional radiation treatment." Both theoretical and experimental work had shown that gold nanoparticles could intensify the effect of radiation. The particles absorb up to 100 times more radiation than tissue. Radiation causes the particles to release a stream of electrons into the area around them. If the particles were in close proximity to cancer cells, that stream of electrons would inflict damage on those cells. "The idea here was to bring this all together, combining the nanoparticles with the delivery system and then irradiating them to see if it had the desired effect," said Leon Cooper, the Thomas J. Watson Sr. Professor of Science at Brown and one of the study's co-authors. Cooper, who shared the Nobel Prize in 1972 for explaining the behavior of electrons in superconductors, has been working for the last several years to better understand biological responses to radiation. Auger effect Gold is an especially good choice for amplifying radiation. When matter is hit by radiation at certain energies, electrons are released through a process known as the photoelectric effect. But gold has an additional source of electron emission, known as the Auger effect, that results from the particular arrangement of electrons orbiting gold atoms. It's the effect of the Auger electrons that the researchers were working to maximize. Working out the quantitative details of the process involved complex calculations and simulations, Cooper said. Auger electrons are low-energy and travel only a very short distance. Their travel distance is so short, in fact, that the electrons may not escape the nanoparticle if the particle is too large. So the researchers had to make sure their particles were small enough to emit those electrons. The short travel distance also means that particles need to be delivered in very close proximity to the cancer cells in order to do damage, hence the need for the pHLIPs. Experiments showed that cancer cells irradiated in the presence of pHLIP-delivered gold had a 24-percent lower survival rate compared to those treated with radiation alone. The pHLIP samples had a 21-percent lower survival compared to irradiation with just gold but no pHLIPs. That suggests that the pHLIPs were effective in getting the gold close enough to the cells to do damage. The next step, the researchers say, is to test the approach in a rodent model, which the team is planning to do soon. "This work is a great example of successful collaboration between Brown and URI," Andreev said. "We hope that the results of this research moving forward will lead to clinical application of pHLIP-based nanotechnology."
Cancer-seeking peptides — pHLIPs — find acidic tumor cells. By attaching gold nanoparticles to pHLIPs, cancer cells receive “antennas” for radiation therapy. Cancer cells (A) treated with gold alone (dark areas) take up far less gold than cells with gold delivered by pHLIPs (B). C and D are cellular close-up with pHLIP-delivered gold. (Images: Reshetnyak and Andreev/URI) "This study was a good proof of concept," said Michael Antosh, assistant professor (research) in Brown's Institute for Brain and Neural Systems and the paper's lead author. "We're encouraged by our initial results and we're excited to take the next step and test this in mice." The team is hopeful that the approach could ultimately improve radiation treatment for cancer patients. By increasing the effectiveness that a given dose of radiation has on cancer, the technique could reduce the overall radiation dose a patient requires, which would in turn reduce side effects. It could also increase the effectiveness of radiation at doses currently administered. Special delivery This research is an extension of work started by Yana Reshetnyak and Oleg Andreev, professors in the URI's Division of Biological and Medical Physics, and professor Donald Engelman of Yale University, the inventors of pHLIP technology. The URI/Yale team had previously developed pHLIPs as a potential delivery system for cancer drugs and diagnostic agents. Cancer cells are generally more acidic than healthy cells, and pHLIPs are natural acid-seekers. "We previously demonstrated that pHLIP-nanogold particles could find and accumulate in tumors established in mice," Reshetnyak said. "Now our task is to test if we can treat cancer by irradiating tumors with nanogold particles more efficiently in comparison with traditional radiation treatment." Both theoretical and experimental work had shown that gold nanoparticles could intensify the effect of radiation. The particles absorb up to 100 times more radiation than tissue. Radiation causes the particles to release a stream of electrons into the area around them. If the particles were in close proximity to cancer cells, that stream of electrons would inflict damage on those cells. "The idea here was to bring this all together, combining the nanoparticles with the delivery system and then irradiating them to see if it had the desired effect," said Leon Cooper, the Thomas J. Watson Sr. Professor of Science at Brown and one of the study's co-authors. Cooper, who shared the Nobel Prize in 1972 for explaining the behavior of electrons in superconductors, has been working for the last several years to better understand biological responses to radiation. Auger effect Gold is an especially good choice for amplifying radiation. When matter is hit by radiation at certain energies, electrons are released through a process known as the photoelectric effect. But gold has an additional source of electron emission, known as the Auger effect, that results from the particular arrangement of electrons orbiting gold atoms. It's the effect of the Auger electrons that the researchers were working to maximize. Working out the quantitative details of the process involved complex calculations and simulations, Cooper said. Auger electrons are low-energy and travel only a very short distance. Their travel distance is so short, in fact, that the electrons may not escape the nanoparticle if the particle is too large. So the researchers had to make sure their particles were small enough to emit those electrons. The short travel distance also means that particles need to be delivered in very close proximity to the cancer cells in order to do damage, hence the need for the pHLIPs. Experiments showed that cancer cells irradiated in the presence of pHLIP-delivered gold had a 24-percent lower survival rate compared to those treated with radiation alone. The pHLIP samples had a 21-percent lower survival compared to irradiation with just gold but no pHLIPs. That suggests that the pHLIPs were effective in getting the gold close enough to the cells to do damage. The next step, the researchers say, is to test the approach in a rodent model, which the team is planning to do soon. "This work is a great example of successful collaboration between Brown and URI," Andreev said. "We hope that the results of this research moving forward will lead to clinical application of pHLIP-based nanotechnology."
These schematics of magnetic domain walls in perpendicularly magnetized thin films show (a) left-handed and (b) right-handed Neel-type walls; and (c) left-handed and (d) right-handed Bloch-type walls. The directions of the arrows correspond to the magnetization direction. The study was carried out at at the National Center for Electron Microscopy (NCEM), which is part of the Molecular Foundry, a DOE Office of Science User Facility. The results have been reported in a s paper ("Unlocking Bloch-type chirality in ultrathin magnets through uniaxial strain"). Electronic Charge and Spin In addition to carrying a negative electrical charge, electrons also carry a quantum mechanical property known as “spin,” which arises from tiny magnetic fields created by their rotational momentum. For the sake of simplicity, spin is assigned a direction of either “up” or “down.” Because of these two properties, a flow of electrons creates both charge and spin currents. Charge currents are well understood and serve as the basis for today’s electronic devices. Spin currents are just beginning to be explored as the basis for the emerging new field of spintronics. Coupling the flows of charge and spin currents together opens the door to yet another new field in electronics called “spin–orbitronics.” The promise of spin-orbitronics is smaller, faster and far more energy efficient devices through solid-state magnetic memory. The key to coupling charge and spin currents lies within magnetic domains, regions in a magnetic material in which all of the spins of the electrons are aligned with one another and point in the same direction – up or down. In a magnetic material containing multiple magnetic domains, individual domains are separated from one another by narrow zones or “walls” that feature rapidly changing spin directions. There are two types of magnetic domain walls known to exist in magnetic thin films: Bloch, in which electron spin rotates like a helical spiral around an axis; and Neel, in which electron spin rotates like a cycloidal spiral. Both types of walls can have either right-handed or left-handed chirality. Applying a technique called SPLEEM, for Spin-Polarized Low Energy Electron Microscopy, to a thin-film of iron/nickel bilayers on tungsten, Chen and Schmid and their collaborators were able to stabilize domain walls that were a mixture of Bloch and Neel types. They also showed how the chirality of domain walls can be switched between left-and right-handedness. This was accomplished by controlling uniaxial strain on the thin films in the presence of an asymmetric magnetic exchange interaction between neighbouring electron spins. “Depending on their handedness, Neel-type walls are propelled with or against the current direction, while Bloch-type walls are propelled to the left or to the right across the current,” Chen says. “Our findings introduce Bloch-type chirality as a new spin texture and might allow us to tailor the spin structure of chiral domain walls. This would present new opportunities to design spin–orbitronic devices.” A key to the success of Chen, Schmid and their colleagues was their SPLEEM imaging technique, which in this country could only be carried out at the Molecular Foundry’s NCEM. “Magnetization is a 3D vector, not just a scalar property and in order to see spin textures, the three Cartesian components of the magnetization must be resolved,” Schmid says. “Berkeley Lab’s SPLEEM instrument is one of a mere handful of instruments worldwide that permit imaging all three Cartesian components of magnetization. It was the unique SPLEEM experimental capability that made this spin-orbitronics research possible.”
Schematic showing the integer quantum Hall effect on the surface of a topological insulator. The effect allows dissipationless current, without energy loss, along the edge of the material. Topological insulators are an unusual type of material, which do not conduct electricity in the inside but only on the surfaces. Their surfaces are populated by massless electrons and electron holes--known as Dirac fermions--which can conduct electricity in a nearly dissipationless fashion, like a superconductor. As a result, their properties are being studied in an intense way with the hope of creating low-power consumption electronic devices. However, impurities in the crystal structures of these topological conductors have, up to now, made it difficult to realize this potential. In the current research, published in ("Quantum Hall Effect on Top and Bottom Surface States of Topological Insulator (Bi
Cross-sectional schematic and top view photograph of the Hall bar device used for the topological insulator. The broken line in the lower panel shows the position of the film shown in the upper panel. In addition, by tuning the external voltage placed on the films, they were able to show that the Dirac states could be switched between the integer quantum Hall state and insulating state by changing the electrical current. According to Ryutaro Yoshimi of the Strong Correlation Physics Research Group, who led the research, "It was very exciting to see this exotic effect in a 3D topological insulator, and we plan to continue our work to show how materials can be finely tuned to have various electronic properties. In the future, these results could I hope be used for the creation of high-speed and low-power-consumption electronic elements."