SCIENCE & TECHNOLOGY CONCENTRATES
BREAKING INTO THE BRAIN
SURGICAL GLUE REPAIRS VESSELS
The blood-brain barrier protects our neurons from potentially harmful substances circulating in blood, but it also impedes delivery to the brain of many potentially life-saving drugs. Researchers led by PerOla Freskgård and Anirvan Ghosh of Hoffmann-La Roche in Basel, Switzerland, report a new tactic for getting drugs to cross this challenging barricade (Neuron 2014, DOI: 10.1016/j.neuron.2013.10.061). They hijacked transport machinery normally used to move essential molecules and nutrients across the blood-brain barrier so that it ferries a potential drug instead. In particular, the team focused on the transferrin receptor, which normally shuttles iron. They attached a potential drug to treat Alzheimer’s disease to an antibody called sFab that binds the transferrin receptor and can be transported across the blood-brain barrier. They showed that the hijacking step enhanced the putative drug’s ability to reach its target behind the barrier by a factor of more than 50. The team argues that their design “could be expanded to other cargos, such as therapeutic growth factors, enzymes, and peptides, and could greatly facilitate the development of a new generation of biotherapeutics for brain disorders.”—SE
The adhesives currently used in surgical applications have many shortcomings. They wash away easily and may be toxic or only weakly adhesive. A team led by bioengineer Jeffrey M. Karp and cardiac surgeon Pedro J. del Nido of Harvard Medical School has developed O O a new surgical glue that avoids these problems O (Sci. Transl. Med. 2014, DOI: 10.1126/scitrans() O 8 lmed.3006557). The new O O n adhesive is made from UV a viscous, spreadO O photoinitiator able precursor to O () O 8 poly(glycerol sebaO O cate acrylate). ExO O posing the material to Precursor O () O ultraviolet light activates 8 cross-linking between the acrylate groups to form a O O n flexible polymer film. The precursor doesn’t immeCross-linked network diately harden in blood and can adhere to wet tissue. Because the glue doesn’t polymerize or adhere until activated, patches coated with it can be repositioned as necessary until they are exposed to UV light. The adhesive is strong enough to withstand the high pressure in blood vessels and to close defects in blood vessels on its own. The researchers used the glue to attach prosthetic patches to repair heart and blood vessel defects in rats and pigs.—CHA
Ideal biocompatible electronics are like Olympic gymnasts: thin and flexible. That’s because devices with thin, flexible substrates can bend to the body’s curves, hugging organs and tissues in a way rigid devices cannot. Now, Giovanni A. Salvatore,
N AT. COMMUN.
CONSTRUCTING GOSSAMER ELECTRONICS
Niko Münzenrieder, and coworkers at ETH Zurich have come up with a new way to make ultraflexible, lightweight, transparent electronics (Nat. Commun. 2014, DOI: 10.1038/ncomms3982). They construct the electronics on substrates made of a poly(p-xylylene) film just 1 µm thick and an underlayer of polyvinyl alcohol. After the fabrication is complete, the underlayer can be dissolved in water, leaving behind a gossamer device that still works when wrapped around a human hair. Because the poly(p-xylylene) is biocompatible, the thin electronics could be incorporated into biomedical devices. For example, the ETH team used the technique to create a thin-film transistor into which they incorporated a strain gauge. They then transferred the device to a contact lens. Such a sensor, they say, could be used to monitor intraocular pressure in glaucoma patient.—BH When a water-soluble underlayer is dissolved, researchers are left with thin, flexible, transparent electronics. CEN.ACS.ORG
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ACTIVATING TITANIUM DIOXIDE WITH VISIBLE LIGHT Many scientists view titanium dioxide as an attractive, low-cost photocatalyst for a variety of applications, including water purification, water splitting, and solar power. But there is a snag: The material catalyzes reactions mainly in response to ultraviolet light. Now, researchers in Singapore have found a way to dope the surface of TiO2 with nitrogen so that the material responds to visible light, drastically increasing its photocatalytic activity (J. Phys. Chem. C 2013, DOI: 10.1021/jp408798f ). Previously used doping methods, such as magnetron sputtering and high-energy ion bombardment, create defects in the bulk TiO2 that reduce the photocatalytic efficiency of the material. But directing a low-energy beam of nitrogen atoms at TiO2 deposits nitrogen on the surface only and keeps the material free of defects, says Junguang Tao, a physicist at the Institute of Materials Research & Engineering, in Singapore. He and his team found that TiO2 doped in this way showed photoactivity when illuminated with visible light, unlike the undoped TiO2. What’s more, the surface-doped TiO2 showed greatly
SCIENCE & TECHNOLOGY CONCENTRATES
enhanced photoactivity under UV illumination, compared with TiO2 doped via other methods.—JNC
for why the bacteria release the vesicles is that they serve as decoys for pathogenic viruses. Another is that the proteins in the vesicles are useful to species of marine microorganisms in symbiosis with Prochlorococcus. Additionally, the vesicles may enable genetic material to be shared among marine microorganisms.—SE
ACOUSTIC TEST FOR MALARIA
BACTERIAL BOUNTY One of the most abundant kinds of marine cyanobacteria is continually releasing an unexpected bounty of protein- and genetic-material-packed vesicles into the ocean, notes a report in Science (2014, DOI: 10.1126/science.1243457). The photosynthetic organisms from the genus Prochlorococcus are responsible for up to 60% of all the chlorophyll a in some marine layers and have a global population that reaches 1027 cells. While examining unusual spherical features in micrographs of the abundant organisms, a team led by Sallie W. Chisholm and Steven J. Biller of MIT discovered that the species release vesicles packed with biomaterial. They confirmed that the process also occurs in the ocean, noting that the vesicles are an unexpected source of marine carbon. One hypothesis
COLORLESS DOPANTS HELP OPTIMIZE OLEDs For several decades scientists have been dreaming of making inexpensive sheets of white organic light-emitting diodes (OLEDs) to serve as lighting tiles and wallpaper. Although some products have reached the market, they don’t yet have all COURTESY OF MARINA PETRUK HINA
Malaria is one of the world’s deadliest diseases, but current tests for the parasite require skilled blood drawing, reagents, and time. Now, Dmitri O. Lapotko of Rice University and colleagues report that they can detect a single parasite-infected blood cell among a million normal cells in seconds, from the sound of bubbles bursting inside the parasite (Proc. Nat. Acad. Sci. USA 2013, DOI: 10.1073/pnas.1316253111). When malaria parasites take up host in a blood cell, they produce a heme-based nanocrystal called hemozoin, which is formed when the parasites digest blood. When bombarded by picosecond near-infrared laser pulses, the nanocrystal generates a transient vapor bubble around itself. The acoustic signature of the bubble popping can then be detected. The test is specific, the authors say: No other biosubstances in the human body produce these bubbles. The method can detect malaria in animals when as few as 0.00034% of cells are infected, they say. The technology could be used for high-throughput tests, fabricated into battery-powered handheld devices, and used by minimally trained nonmedical field staff in areas heavily affected by malaria. Human trials of the technology will start this year, the authors say.—EKW
This copper(I) pentafluorobenzoate complex, shown superimposed on a white OLED tile, serves as a colorless dopant for OLED hole-transport layers. Cu = blue-green, F = green, O = red, and C = gray.
the desired properties. One goal has been to develop a fully transparent hole-transport layer. Tungsten or molybdenum oxides and fluorinated tetracyanoquinodimethanes are dopant molecules typically used for this layer. But these colored compounds lead to undesired hues and reduce optical efficiency. A team led by Günter Schmid of the electronics company Siemens AG in Erlangen, Germany, and Marina A. Petrukhina of SUNY Albany have now devised fluorinated copper(I) carboxylates as colorless dopants for the hole-transport layer (Adv. Mater. 2013, DOI: 10.1002/adma.201303252). The dopant normally interacts with a polyaromatic amine electron hole conductor, CEN.ACS.ORG
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generating delocalized holes that travel to phosphorescent or fluorescent dyes in an adjacent layer where the light is emitted. The team showed that copper(I) pentafluorobenzoate interacts sufficiently with the amine to stimulate hole transport but not so strongly as to induce charge transfer in the visible region to produce the unwanted color. The German lighting company Osram has used the new dopants to make OLED prototypes that perform as well as previous versions but with transparent hole-transport layers and higher power efficiency.—SR
TWEAKING ACETYLS HALTS DIABETES IN MICE Acetyl groups on lysine residues are chemical master switches that control myriad activities in cells. Acetylation is best known for its involvement in gene transcription and cancer progression. In fact, FDA in 2006 approved vorinostat, a molecule that blocks the removal of acetyl groups from lysine residues, to treat a type of lymphoma. Acetylation also influences inflammation, so researchers are investigating whether vorinostat and similar drugs could treat autoimmune diseases such as type 1 diabetes. Now, a multi-institution team has reduced the occurrence of type 1 diabetes in mice by feeding them vorinostat or another lysine deacetylase inhibitor, givinostat (Proc. Natl. Acad. Sci. USA 2014, DOI: 10.1073/pnas.1320850111). The researchers, led by Thomas Mandrup-Poulsen of the University of Copenhagen, also learned that the compounds delay the mice’s onset of diabetes. The effective doses were two orders of magnitude lower than those given for cancer treatment, Mandrup-Poulsen says. The drugs can be taken orally, so patients may be more likely to follow that regimen compared with insulin injections. The authors think this study lays some groundwork for clinical trials in type 1 diabetes patients, but they call for more safety studies on vorinostat first.—CD O
H N O
N H
OH
Vorinostat
N
H N
O
H N
O Givinostat
O
OH