GETTING THE “HOLE” STORY ON NUCLEIC ACID NANOPARTICLES Nucleic acid nanoparticles (NANPs) are structures that selfassemble through programmed structuring into a variety of shapes and sizes, with differing internal connectivities and physicochemical properties. Their properties give these particles promise in a range of applications in medicine and biotechnology. To facilitate these uses, researchers must have a way to detect NANPs and to characterize them at the single-particle level. One way to accomplish this goal is through voltage-driven passage of these analytes through a nanopore, which can deliver information about NANPs through their occlusion of an ionic current. Alibakhshi et al. (DOI: 10.1021/acsnano.7b04923) test this idea in a new study involving hollow and flexible RNA ring- and DNA cube-shaped NANPs at picomolar concentrations. Using solid-state nanopores with diameters between 9−10 nm, just smaller than the size of the NANPs, the researchers first confirmed this system’s ability to detect the ring-shaped particles, which are formed via RNA−RNA tertiary interactions known as kissing loops. They observed longer dwell times at a higher electrical bias, which appeared necessary for the NANPs to translocate through the pore rather than collide with it. This system also reliably detected the cube-shaped DNA NANPs, showing that the cubes can cause a larger current blockade than the rings. Further experiments with a mixture of the two NANP types showed that this difference could be used to distinguish between the blocks and rings. Molecular dynamics simulations confirmed these experimental findings. The authors suggest that nanopore-based sensing could offer a multiplexed detection platform for characterizing NANPs, even mixtures of these particles at picomolar concentrations.
The researchers crafted these particles based on linear poly(2hydroxypropyl)-methacrylamide polymers and either tetrasaccharide sialyl-LewisX (SLeX), a sulfated form of SLeX; SLeX decorated with randomly linked carbohydrates; or the latter with additional sulfation. Experiments show that each of these glycloproteins effectively bind in vitro to primary human macrophages without activating them and to primary human blood leukocytes, but only bind poorly to fibroblast and endothelial cells. In vivo experiments in mice showed that these nanoparticles accumulated in the liver without causing hepatotoxicity. However, the non-sulfated binder decorated with randomly linked carbohydrates best protected mice against acute toxic liver injury in two different models of hepatitis. In contrast, the sulfated form of this selectin binder induced a decrease in infiltrating and resident macrophages and an increase in T helper cells, aggravating liver injury. The authors suggest that the nonsulfated selectin-binding glycoprotein nanoparticles could hold promise as immunotherapities for inflammatory liver diseases and liver cancer.
MIMICKING FROG FEET WITH NANO- AND MICROPILLARS Several different biological materials contain micro- or nanoscale anisotropic building blocks oriented in ways that enhance directional reinforcement in the bulk material, such as the collagen fibers of musculoskeletal tissue, the cellulose fibers of wood, and the inorganic platelets of mollusk shells. Some keratinized or cornified epithelia also display the same anisotropic characteristics. One example is the composite structure of the adhesive pads in the toe pads of tree and rock frogs. These structures are composed of arrays of soft epithelial cells separated by narrow channels, crossed by densely packed hard keratin nanofibers. Previous studies have shown that this composition is key to enhancing adhesion and friction on humid and flooded surfaces. However, the benefit of the embedded unidirectional nanofibers in this microcomposite structure has been unclear. To investigate, Xue et al. (DOI: 10.1021/acsnano.7b04994) fabricated frog-toe-mimicking arrays of polydimethylsiloxane (PDMS) micropillars embedded with polystyrene (PS) nanopillars using a multistep process. The result was anisotropic, multicomponent micropatterns embedded with aligned nanofibers. The researchers characterized the adhesion and friction
NANOPARTICLES TO REDUCE LIVER INFLAMMATION Various immunotherapies are currently being explored as treatments for inflammatory diseases and cancer. One strategy involves targeting selectins, molecules that control the first step in immune cell adhesion and extravasation by guiding leukocyte trafficking into tissue lesions. Selectin-blocking therapies are already in clinical trials to treat chronic obstructive pulmonary disease and sickle cell disease. Despite the promise of these therapies, selectin binders have not yet been explored for inflammatory liver injuries and diseases. Bartneck et al. (DOI: 10.1021/acsnano.7b04630) investigate this possibility with selectin-binding glycopolymer nanoparticles. © 2017 American Chemical Society
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Published: October 24, 2017 9570
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behavior of these arrays using a spherical ruby probe. Results showed that the adhesion force of PDMS arrays composed with the PS nanopillars was significantly higher than that of arrays without this component. Further experiments showed that the PS nanopillars homogeneously distributed stress on the pillar tops and efficiently transferred it to the backing PDMS layers. Consequently, this hierarchical structure appears to be beneficial for both adhesion and friction, factors that could also be critical in tree frog toe pads. The authors suggest that this design could hold potential for bio-inspired materials that utilize these qualities.
A NEW WAY TO APPLY MULTILAYER COATINGS The layer-by-layer (LbL) assembly approach to applying multilayer coatings has been in use for more than two decades. This technique enables fine control over film thickness at the nanometer scale using cyclic depositions. However, LbL assembly is notoriously time-consuming, with each layer taking tens of minutes to deposit; consequently, it is typically employed for coatings less than 100 nm thick. Variations of this technique are more efficient, but trade off uniformity on large scales and the ability to apply coatings to nonplanar surfaces. Seeking a way to apply micron-thick coatings efficiently on substrates of arbitrary materials and shapes, Zhao et al. (DOI: 10.1021/acsnano.7b03480) developed a method that they call ion diffusion-directed assembly (IDDA). The researchers adsorbed electrolytes such as CaCl2, BaCl2, and CuSO4 onto various substrates, then immersed these items into a dispersion of graphene oxide (GO) sheets. They found that the cations from the electrolytes diffused immediately into the GO dispersion, forming a GO gel layer along the substrate surfaces due to electrostatic interaction and coordination bonding between the negatively charged GO sheets and the cations. With ongoing diffusion, this gel layer at the substrate grows continuously thicker until all the cations are captured. Consequently, the coating thickness can be controlled by both the ion type and amount as well as the GO concentration. The researchers show that this method produced stable GO coatings on substrates of a variety of materials, including glass, metal, wood, plastic, and pottery, as well as substrates of any shape. The authors suggest that this method could be extended to other types of coatings, including polymers and colloidal nanoparticles.
ATTACKING INFLAMMATORY BOWEL DISEASE THE NANO WAY About two of every thousand individuals in developed countries have a type of inflammatory bowel disease (IBD), autoimmune disorders of the intestinal tract that manifest with acute and chronic inflammation, tissue injury, scarring, and predisposition to adenocarcinoma. These conditions, which include Crohn’s disease and ulcerative colitis, are currently treated with a variety of immune suppressants and biologicals. However, these methods are fraught with potential complications, including systemic immunosuppression and other toxicities. One alternative to these treatments is to take advantage of the inflammatory- and immunoregulatory-suppressing mechanisms that enteric bacterial pathogens have developed over the millennia. However, no current IBD treatments target these pathways due to difficulties with delivering these immunomodulating proteins without compromising their biological activity. Herrera Estrada et al. (DOI: 10.1021/acsnano.7b03239) get around this conundrum by making nanoparticles of AvrA, an immunomodulating protein derived from Salmonella. Using a desolvation process, the researchers created condition-responsive cross-linked protein nanoparticles that can un-cross-link in the reducing environment inside cells. By adding enhanced green fluorescent protein to these nanoparticles, the researchers saw that they were readily internalized by epithelial cells both in vitro and in vivo and inhibited inflammatory signaling pathways. In mouse models of IBD, experiments showed anti-inflammatory activity both with prophylactic treatment and after symptoms developed. The researchers suggest that these promising results could spur work to develop clinically relevant oral formulations. Additional studies, they add, might also investigate the effects of combination therapies that incorporate other bacterial proteins, human cytokines, or small-molecule anti-inflammatory agents.
DOING THE WAVE FOR STEM CELL ADHESION AND DIFFERENTIATION Cell adhesion, a process critical both for forming threedimensional structures during development as well as tumor spread in cancer, is regulated by interactions between cells and the extracellular matrix (ECM). One of these interactions is the binding of cell surface receptors, such as integrin, to their recognition ligands, such as the arg-Gly-Asp (RGD) tripeptide sequence found in ECM components including fibronectin, vitronectin, and collagen. Recent reports have suggested that it is possible to control this interaction remotely by the application of various stimuli, such as light. However, light’s limited tissue penetration restricts the utility of this application in vivo. 9571
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Seeking a different way to control cell adhesion remotely, Kang et al. (DOI: 10.1021/acsnano.7b02857) looked to magnetic fields, which penetrate living tissues with significantly less absorption than light, thus enabling widespread and prolonged applications in vivo. The researchers tethered RGD ligands to superparamagnetic iron oxide nanoparticles, which were in turn coupled to a substrate by long poly(ethylene glycol) linkers. By applying magnetic fields, the researchers were able to evaluate how different frequencies affect cell adhesion both in vitro and in vivo. Results in cell culture experiments and in live mice showed that a low oscillation frequency (0.1 Hz) promoted integrinRGD binding and adhesion of human mesenchymal stem cells, but frequencies of 2 Hz stymied them. These effects were reversible. Further experiments showed that low frequencies also promote differentiation. The authors suggest that this platform not only provides a way to study integrin−RGD interactions in vitro but also a way to manipulate and to study cell adhesion in vivo.
SHEDDING LIGHT ON OPTICAL PRINTING In recent years, research on colloidal nanoparticles has resulted in a vast diversity of these materials, with various physical, chemical, and biological properties. However, colloidal nanoparticles are obtained in liquid suspensions. One challenge in using these materials to their fullest potential is finding a way to assemble them onto substrates in precise, ordered arrays. Several approaches toward this end have been developed, including convective self-assembly or Langmuir−Blodgett methods and template-assisted methods. However, these techniques come with several drawbacks, including limited versatility in forming arbitrary arrays, lengthy or complicated fabrication procedures, or the inability to combine multiple particle types in the same array. Optical printing, which uses optical forces to capture colloidal nanoparticles directly from suspension and to deposit them on specific locations of a substrate, could offer a way around these challenges. How to obtain the highest precision with this method as well as the roles of localized surface plasmon resonances (LSPRs) have been unclear. Gargiulo et al. (DOI: 10.1021/acsnano.7b04136) investigate these questions in an optical printing setup using Au and Ag nanoparticles and different laser powers and wavelengths. Their findings show that when the wavelength is tuned to the LSPR of the nanoparticles, the accuracy of optical printing improves as the laser power is reduced. However, for wavelengths off the LSPR, the accuracy is independent of the laser power. Calculations that incorporate optical forces, electrostatic forces, and Brownian motion confirm these experimental findings. The authors suggest that these findings expand the understanding of processes behind optical printing and could be used to help optimize this technique in the future.
MOS2 MONOLAYERS SEE THE LIGHT Controlling light in integrated circuits is pivotal to developing high-speed electro-optic devices. Toward that goal, two areas have attracted growing attention. One area is the extraordinary properties of transition metal dichalcogenides (TMDCs). MoS2 monolayers, in particular, have drawn growing interest due to their direct electronic band-gap structure, versatile optical transitions, and tunable mechanical properties. In addition, tightly bound excitons in this material could help realize electrooptic devices that operate in the visible spectral region. Another area that could contribute toward better manipulation of light is plasmonic nanostructures, which confine light at the nanoscale and enhance the electromagnetic field. Li et al. (DOI: 10.1021/acsnano.7b05479) combined these two materials to create a nanoplasmonic modulator in the visible spectral region. On chemical vapor deposition-grown monolayers of MoS2, the researchers fabricated a Au nanodisk using electron-beam lithography following Au evaporation. They then added Ti and Au electrodes to improve the conductivity of the contact between these two. Experiments show that when the narrow MoS2 excitons are coupled with the broad Au plasmons under the excitation of incident light, the result is a deep Fano resonance that can be switched on and off by applying different gate voltages on the MoS2 monolayers. Taking advantage of this phenomenon, the researchers fabricated a two-dimensional display device by patterning Au nanodiscs as an array on MoS2 monolayers. The authors suggest that this work provides an effective way to manipulate the exciton−plasmon interaction actively, offering a possible solution for ultrathin and nanoscale electro-optic devices in the future.
A p−n JUNCTION LIKE NO OTHER Topological insulators are a new class of quantum matter that behaves as an insulator in the interior but has unusual surface electronic states that act as conductors. These topological surface states (TSSs) form a Dirac band with their spins locked helically with momentum, offering extraordinary potential for spintronics and error-tolerant quantum computing. To achieve these applications, these materials need to be fabricated into devices bearing p−n junctions. Such topological p−n junctions could 9572
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have intriguing electrical properties, such as the junction electronic state and spin rectification. However, fabricating these unique p−n junctions has presented numerous challenges involving materials, process, and fundamental reasons. Kim et al. (DOI: 10.1021/acsnano.7b03880) find a way around these challenges by developing a topological p−n junction with an atomically abrupt interface. On the surface of a cleaved Bi2Se3 crystal with a typical n-type TSS, the researchers deposited Sb at sub-bilayer concentrations. At a coverage of about 0.9 bilayers, roughly half the crystal surface became covered with Sb islands of a few hundred nanometers in width with heights of about 2 bilayers. Because of the p-type character of the Sb’s TSS, this hybridization forms p−n junctions across the crystal surface. Angle-resolved photoemission spectroscopy and scanning tunneling spectroscopy show that the n- and p-type TSSs are separated by atomic step edges, the most abrupt junction possible in a crystal, with a lateral electronic junction as short as 2 nm. The authors suggest that the approach used to create these unusual topological p−n junctions could accelerate the development of various electronic and spintronic devices scalable down to atomic dimensions.
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