Responding to the radiation threat

 The New York Times recently reported that in the darkest moments of the triple meltdown last year of the Fukushima Daiichi nuclear power plant, Japanese officials considered the evacuation of the nearly 36 million residents of the Tokyo metropolitan area. The consideration of so drastic an action reflects the harsh fact that in the aftermath of a major radiation exposure event, such as a nuclear reactor accident or a "dirty bomb" terrorist attack, treatments for mass contamination are antiquated and very limited.

The only chemical agent now available for decontamination -- a compound known as DTPA -- is a Cold War relic that must be administered intravenously and only partially removes some of the deadly actinides -- the radioactive chemical elements spanning from actinium to lawrencium on the periodic table -- that pose the greatest health threats.

Scientists at the U.S. Department of Energy (DOE)'s Lawrence Berkeley National Laboratory (Berkeley Lab) are developing a much more effective alternative that decontaminates a large number of the actinides likely to be part of the radiation exposure from a nuclear plant or weapon, including plutonium, americium, curium, uranium and neptunium. Furthermore, the Berkeley Lab treatment can be administered orally in the form of a pill, a necessity for prompt treatment in the event of mass contamination. Depending on the level of radiation exposure and how soon treatment can start, one of these pills would result in the excretion of approximately 90-percent of the actinide contaminants within 24 hours. Taking one pill daily for two weeks should be enough to remove virtually all of the actinide contaminants.

"With the expanding use of nuclear power and unfortunate possibility of nuclear weapon use, there is an urgent need to develop and implement an improved therapy for actinide contamination of a large population," says Rebecca Abergel, a chemist who leads the Bioactinide Group at Berkeley Lab's Glenn T. Seaborg Center. "We are now in the process of demonstrating that our actinide-specific decontaminating agents are ready for clinical development."

Once actinides are ingested or inhaled, their radioactivity and cancerous interactions with cells and tissue demand they be immobilized and removed from the body as soon as possible. Abergel and her group are part of an effort at Berkeley Lab that began more than two decades ago under the leadership of Ken Raymond, a chemist who holds joint appointments with Berkeley Lab and the University of California (UC) Berkeley, where he is the Chancellor's Professor of Chemistry, in collaboration with the late Patricia Durbin. The primary goal of this project has been to identify sequestering agents that can encapsulate actinides into tightly bound cage-like chemical complexes for transport out of the body. The early focus of this research was on plutonium, the alpha particle-emitting actinide discovered by Berkeley Lab Nobel laureate Glenn Seaborg, and natural chelators, the crablike molecules that specifically bind with iron and other metal ions.

"Since the biochemical properties of plutonium(IV) and iron(III) are similar, we modeled our sequestering agents after the chelating unit found in siderophores," Raymond says. Siderophores are small molecules secreted by bacteria to extract and solubilize iron. "This biomimetic approach enabled us to design multidentate hydroxypyridonate ligands that are unrivaled in terms of actinide-affinity, selectivity and efficiency."

The two best candidate hydroxypyridonate ligands -- nicknamed HOPO -- developed by Abergel and her colleagues are a tetradentate, which has four chelating arms, and an octadentate, which has eight chelating arms. The "arms" in this case are atoms with pairs of electrons available for covalent bonding with an actinide.

"We've advanced our two candidate ligands through the initial phases of pre-clinical development by successfully scaling up synthesis to the 5-kilograms level and establishing baseline preparation and analytical methods suitable for manufacturing larger amounts under good manufacturing practice guidelines," Abergel says.

The team has also carried out extensive studies in animal models and human cell lines that established the two HOPO candidates as being highly effective and non-toxic at the tested doses. As for comparisons between the two, each has its own merits.

"A single octadentate HOPO can form a full actinide complex and results in more total actinide excretion," Abergel says. "However, it is easier for the smaller tetradentate HOPO to pass through biological membranes and access desired target sites in the body. Both warrant further development for emergency use in the case of a radiological event."

Abergel says the basic research and development phase of these two candidates has been completed and she and her group have started the process with the U.S. Food and Drug Administration (FDA) to determine what further data is needed to move into clinical trials. Typically at this stage of development a private pharmaceutical company would step in but it is difficult to attract private investors for a drug that will hopefully never be needed.

"As we move further along with the FDA process it should be easier to convince private pharmaceutical companies to get involved," Abergel says.

In addition to Abergel, Raymond and Durbin, other researchers who are or have been involved in this project include Dahlia An, Kathleen Bjornstad, Eleanor Blakely, Deborah Bunin, Polly Chang, Shirley Ebbe, Erin Jarvis, Birgitta Kullgren, Chris Rosen, David Shuh, Manuel Sturzbecher-Hoehne and Jide Xu.

There have been several scientific papers published about this work with the most recent being "Multidentate terephthalamidate and hydroxypyridonate ligands: towards new orally active chelators," in the journal Hemoglobin. It was written by Abergel and Raymond.

This research was primarily supported by the National Institutes of Health through the National Institute of Allergy and Infectious Diseases and the Rapid Access to Interventional Development Program. Support also came from the DOE Office of Science.

Story Source:

The above story is reprinted from materials provided by DOE/Lawrence Berkeley National Laboratory.

Note: Materials may be edited for content and length. For further information, please contact the source cited above.

Journal Reference:

Rebecca J. Abergel, Kenneth N. Raymond. Multidentate Terephthalamidate and Hydroxypyridonate Ligands: Towards New Orally Active Chelators. Hemoglobin, 2011; 35 (3): 276 DOI: 10.3109/03630269.2011.560771

Nanomaterials: A coating protocol

A robust approach for preparing polymer-coated quantum dots may find use in a wide range of applications.

Quantum dots (QDs) are tiny crystals of semiconducting material that produce fluorescence. The color or the wavelength of the fluorescence is dependent on the size, shape and composition of QDs. Larger QDs tend to emit light at the red end (longer wavelengths) of the electromagnetic spectrum. As the size of the QDs decrease, so does the wavelength of emitted light. This tunability of emission wavelength is one reason why QDs have become popular for use as fluorescent markers in biological research. For example, scientists can attach QDs to single molecules and cells and track their movements over time using fluorescence microscopy.

Dominik Jańczewski, Nikodem Tomczak and Ming-Yong Han at the A*STAR Institute of Materials Research and Engineering and co-workers1 have now described a protocol for the preparation of quantum dots coated with an amphiphilic polymer -- a polymer that contains both water-attracting and -repelling components. "Our aim is to develop a robust approach for the preparation of QD for use as fluorescent tags for bioimaging, sensing and therapeutics," says Han. "The method we have developed is applicable to any nanoparticles, not just QDs."

Most biological applications require the use of QDs that disperse and remain stable in an aqueous solution. Conventional approaches for synthesizing QDs typically endow the QDs with a coating of hydrophobic ligands, which are repelled by water. Although it is possible to exchange the ligands after synthesis, a ligand shell that is exchangeable is, by its very nature, unstable and might result in the release of toxic materials, such as cadmium, into solution.

Instead of exchanging the ligands, an alternative method to make the QDs disperse in water is to coat them with a polymer that has both hydrophilic and hydrophobic parts. This works on the simple principle that like attracts like -- or in other words, hydrophobic parts of the polymer attract hydrophobic ligands that stabilize the QDs, and hydrophilic parts of the polymer attract water molecules in solution.

The new protocol describes the procedure in detail and aims to provide the benefits of the research team's experience in QD synthesis to others whose interests might be focused more on applications rather than the development of synthetic methods. The synthesis of the polymer coating allows the incorporation of a wide variety of functional groups. "In the future we hope to work towards image guided therapy," says Han. "QDs could be prepared that not only produce an image of cancer cells, but also release drugs at such a target."

Story Source:

The above story is reprinted from materials provided by The Agency for Science, Technology and Research (A*STAR), via ResearchSEA.

Note: Materials may be edited for content and length. For further information, please contact the source cited above.

Journal Reference:

Dominik Jańczewski, Nikodem Tomczak, Ming-Yong Han, G Julius Vancso. Synthesis of functionalized amphiphilic polymers for coating quantum dots. Nature Protocols, 2011; 6 (10): 1546 DOI: 10.1038/nprot.2011.381

Diagnostic tool: Polymer film loaded with antibodies can capture tumor cells

 The development of polymer film loaded with antibodies that can capture tumor cells shows promise as a diagnostic tool. Cancer cells that break free from a tumor and circulate through the bloodstream spread cancer to other parts of the body. But this process, called metastasis, is extremely difficult to monitor because the circulating tumor cells (CTCs) can account for as few as one in every billion blood cells.

Research led by scientists at the RIKEN Advanced Science Institute in Wako, in collaboration with colleagues at the University of California, Los Angeles, and the Institute of Chemistry at the Chinese Academy of Sciences, Beijing, has produced a polymer film that can capture specific CTCs1. With further development, the system could help doctors to diagnose an advancing cancer and assess the effectiveness of treatments.

The researchers used a small electrical voltage to help deposit a conducting polymer film of poly(3,4-ethylenedioxythiophene) (PEDOT) bearing carboxylic acid groups on to a 2-centimeter-square glass base (Fig. 1). The polymer formed nanodots, tiny bumps that measure 100 to 300 nanometers across, depending on the voltage used (1-1.4 V).

Adding a chemical linker to the film allowed it to bind a protein called streptavidin; this protein then joined to an antibody. In turn, the antibody could latch on to an antigen called epithelial cell adhesion molecule (EpCAM), which is produced by most tumor cells. In this way, the film could grab tumor cells from just a few milliliters of a blood sample.

The team tested several types of tumor cells on films with various sizes and densities of nanodots, and used a microscope to observe how well they captured the cells. The most effective film, with nanodots measuring about 230 nanometers across and containing about 8 dots per square micrometer, captured roughly 240 breast-cancer cells per square millimeter of film. In contrast, it caught fewer than 30 cervical cancer cells that do not express EpCAM, proving that the antibody used on the film is highly selective. A smooth PEDOT-carboxylic acid film with the same antibody captured only 50 or so breast cancer cells.

The film's efficiency depends on the size and spacing of the nanodots, and the presence of the capturing antibody. Since these can be easily modified, the same method could be used to make films that sense other types of cells.

The next step is to "further optimize the nanostructures of the conducting polymers and understand in more detail the cell-capturing mechanism," says RIKEN unit leader Hsiao-hua Yu. "We are also currently working on a direct electrical readout of the captured cells, without needing to use a microscope."

The corresponding author for this highlight is based at the Yu Initiative Research Unit, RIKEN Advanced Science Institute

Story Source:

The above story is reprinted from materials provided by RIKEN, via ResearchSEA.

Note: Materials may be edited for content and length. For further information, please contact the source cited above.

Journal Reference:

Jun Sekine, Shyh-Chyang Luo, Shutao Wang, Bo Zhu, Hsian-Rong Tseng, Hsiao-hua Yu. Functionalized Conducting Polymer Nanodots for Enhanced Cell Capturing: The Synergistic Effect of Capture Agents and Nanostructures. Advanced Materials, 2011; 23 (41): 4788 DOI: 10.1002/adma.201102151

Origami-inspired paper sensor could test for malaria and HIV for less than 10 cents, report chemists

 Inspired by the paper-folding art of origami, chemists at The University of Texas at Austin have developed a 3-D paper sensor that may be able to test for diseases such as malaria and HIV for less than 10 cents a pop. The sensors can be printed out on an office printer, and take less than a minute to assemble.

Such low-cost, "point-of-care" sensors could be incredibly useful in the developing world, where the resources often don't exist to pay for lab-based tests, and where, even if the money is available, the infrastructure often doesn't exist to transport biological samples to the lab.

"This is about medicine for everybody," says Richard Crooks, the Robert A. Welch Professor of Chemistry.

One-dimensional paper sensors, such as those used in pregnancy tests, are already common but have limitations. The folded, 3-D sensors, developed by Crooks and doctoral student Hong Liu, can test for more substances in a smaller surface area and provide results for more complex tests.

"Anybody can fold them up," says Crooks. "You don't need a specialist, so you could easily imagine an NGO with some volunteers folding these things up and passing them out. They're easy to produce as well, so the production could be shifted to the clientele as well. They don't need to be made in the developed world."

The results of the team's experiments with the origami Paper Analytical Device, or oPAD, were published in October in the Journal of the American Chemical Society and this week in Analytical Chemistry.

The inspiration for the sensor came when Liu read a pioneering paper by Harvard University chemist George Whitesides.

Whitesides was the first to build a three-dimensional "microfluidic" paper sensor that could test for biological targets. His sensor, however, was expensive and time-consuming to make, and was constructed in a way that limited its uses.

"They had to pattern several pieces of paper using photolithography, cut them with lasers, and then tape them together with two-sided tape," says Liu, a member of Crooks' lab. "When I read the paper, I remembered when I was a child growing up in China, and our teacher taught us origami. I realized it didn't have to be so difficult. It can be very easy. Just fold the paper, and then apply pressure."

Within a few weeks of experiments, Liu had fabricated the sensor on one simple sheet using photolithography or simply an office printer they have in the lab. Folding it over into multiple layers takes less than a minute and requires no tools or special alignment techniques. Just fingers.

Crooks says that the principles underlying the sensor, which they've successfully tested on glucose and a common protein, are related to the home pregnancy test. A hydrophobic material, such as wax or photoresist, is laid down into tiny canyons on chromatography paper. It channels the sample that's being tested -- urine, blood, or saliva, for instance -- to spots on the paper where test reagents have been embedded.

If the sample has whatever targets the sensor is designed to detect, it'll react in an easily detectable manner. It might turn a specific color, for instance, or fluoresce under a UV light. Then it can be read by eye.

"Biomarkers for all kinds of diseases already exist," says Crooks. "Basically you spot-test reagents for these markers on these paper fluidics. They're entrapped there. Then you introduce your sample. At the end you unfold this piece of paper, and if it's one color, you've got a problem, and if not, then you're probably OK."

Crooks and Liu have also engineered a way to add a simple battery to their sensor so that it can run tests that require power. Their prototype uses aluminum foil and looks for glucose in urine. Crooks estimates that including such a battery would add only a few cents to the cost of producing the sensor.

"You just pee on it and it lights up," says Crooks. "The urine has enough salt that it activates the battery. It acts as the electrolyte for the battery."

Story Source:

The above story is reprinted from materials provided by University of Texas at Austin.

Note: Materials may be edited for content and length. For further information, please contact the source cited above.

Journal Reference:

Hong Liu, Richard M. Crooks. Paper-Based Electrochemical Sensing Platform with Integral Battery and Electrochromic Read-Out. Analytical Chemistry, 2012; 84 (5): 2528 DOI: 10.1021/ac203457h

Note: If no author is given, the source is cited instead.

Disclaimer: This article is not intended to provide medical advice, diagnosis or treatment. Views expressed here do not necessarily reflect those of ScienceDaily or its staff.

Squeezing silicone polymers produces chemical energy, but raises doubts about implant safety

 A polymer is a mesh of chains, which slowly break over time due to the pressure from ordinary wear and tear. When a polymer is squeezed, the pressure breaks chemical bonds and produces free radicals: ions with unpaired electrons, full of untapped energy. These molecules are responsible for aging, DNA damage and cancer in the human body.

In a new study, Northwestern University scientists turned to squeezed polymers and free radicals in a search for new energy sources. They found incredible promise but also some real problems. Their report is published by the journal Angewandte Chemie.

The researchers demonstrated that radicals from compressed polymers generate significant amounts of energy that can be used to power chemical reactions in water. This energy has typically been unused but now can be harnessed when polymers are under stress in ordinary circumstances -- as in shoe soles, car tires or when compacting plastic bags.

They also discovered during the study that a silicone polymer commonly used in implants for cosmetic procedures releases a large quantity of harmful free radicals when the polymer is under only a moderate amount of pressure. These findings suggest the safety of certain polymer-based medical implants should be looked at more closely.

"We have established that polymers under stress create free radicals with overall efficiencies of up to 30 percent and shoot the radicals out into the surrounding medium where they can drive chemical reactions," said Bartosz A. Grzybowski, an author of the paper and the Kenneth Burgess Professor of Physical Chemistry and Chemical Systems Engineering. "These radicals can be useful or they can be harmful, depending on the situation."

Grzybowski and his team are the first to use this energy to drive chemical reactions by simply surrounding the compressed polymer with water containing desired reagents.

The radicals created in the polymer migrate toward the polymer/water interface where they produce hydrogen peroxide, which then can drive chemical processes.

"You can get a surprisingly large amount of chemical energy from a polymer under compression," Grzybowski said. "This energy is, in a sense, free for the taking. Under normal circumstances, the energy is virtually never retrieved from deformed polymers, which then age unproductively. But you could recharge a battery from the energy produced by walking or driving a car. And you could capture even more energy when compacting millions of plastic bags."

Grzybowski is also director of Northwestern's Non-Equilibrium Energy Research Center, which is funded by the U.S. Department of Energy.

"We are interested in new sources of chemical energy, and this energy from the simple breaking of polymers' bonds is not being used," he said. "By surrounding the polymer with a medium, such as water, we can produce environmentally friendly chemical energy. One direction we are pursuing is to use this energy to sanitize water in developing countries. This is possible because hydrogen peroxide produced by squeezed polymers kills bacteria."

The researchers confirmed that mechanical deformation -- moderate squeezing -- created free radicals in the polymers. They also determined the number of radicals produced in a polymer under pressure is approximately 1016 (10 to the 16th) radicals per cubic centimeter of polymer -- a substantial amount.

They next filled polymer tubes with water, squeezed the tubes and measured the total number of radicals that migrated into the surrounding solution. They found that nearly 80 percent of the radicals made the trip.

Grzybowski and his team demonstrated they can squeeze a polymer, such as what might be found in a shoe, tire or plastic bag, and get a mechanical-to-chemical energy conversion of up to 30 percent -- approaching the energy efficiency of a car engine.

The hydrogen peroxide produced when a polymer surrounded by water is squeezed can power a variety of chemical reactions, including fluorescence, nanoparticle synthesis and dye bleaching, the researchers showed.

To illustrate the process, they converted a Nike Air LeBron shoe into a "lightning shoe," where the air pockets in the polymeric sole are filled with a solution of a compound that lights up in the presence of radicals. After a person walked in the shoe for 30 minutes or more, enough radicals were created to generate a blue glow visible to the naked eye.

The researchers studied seven different polymers, including a number of particular public interest. Poly(dimethylsiloxane), a silicon-based material commonly used in medical implants, was one of them. In the lab experiments, the medium surrounding the polymer and the amount of pressure exerted on the material were similar to what would be found in the human body, Grzybowski pointed out.

"Our findings are somewhat worrisome since every polymeric implant in the human body experiences mechanical stresses and, as we now know, can produce harmful free radicals and liberate them into surrounding tissues, which may contribute to diseases such as cancer, stroke, myocardial infarction, diabetes and other major disorders," Grzybowski said. "With this knowledge, I am quite happy to have a metal implant in my knee, rather than a polymer implant.

"From a scientific perspective, our work proves yet again that a phenomenon can be useful or harmful depending on how we implement it," he said. "The same polymer can be a useful source of energy when outside of a human body, yet a potential risk hazard when implanted into it."

Story Source:

The above story is reprinted from materials provided by Northwestern University. The original article was written by Megan Fellman.

Note: Materials may be edited for content and length. For further information, please contact the source cited above.

Journal Reference:

H. Tarik Baytekin, Bilge Baytekin, Bartosz A. Grzybowski. Mechanoradicals Created in “Polymeric Sponges” Drive Reactions in Aqueous Media. Angewandte Chemie, 2012; DOI: 10.1002/ange.201108110