BUBBLE, BUBBLE, TRAPPING NANO-OBJECTS? NO TROUBLE Several fields, including biodynamics, environmental and pollution control, and early diagnostics in medicine, require highly sensitive investigations of small amounts of molecules, moieties, or nano-objects dispersed in solution. Typically, when dealing with nanostructured devices with small areas, the average time necessary to detect an event increases as the solute concentration decreases. Although several techniques have been developed to process highly diluted samples down to the single-molecule limit, many have significant drawbacks. One such drawback is the inability to maintain physiological conditions, which can damage highly vulnerable but useful biological materials, such as exosomes, extracellular membrane vesicles that have shown promise in cancer diagnostics and prognosis. Seeking a better way to concentrate analytes in solution, Tantussi et al. (DOI: 10.1021/acsnano.7b07893) investigated capturing them with rapidly expanding microbubbles. The researchers developed a platform in which vertical plasmonic nanoantennae illuminated with short laser pulses generate gas bubbles in solution, which quickly expand and concentrate analytes at the solution−gas interface. A vertical panel in close proximity to each antenna prevents each generated bubble from following random kinetic pathways, essentially guiding it to a “basket” on the other side. When the bubbles alight on the basket, they collapse and deposit collected items inside. Proof-ofprinciple experiments showed that this method could be used to capture nanosized exosome vesicles dispersed in water, which were then analyzed with Raman spectroscopy. The authors suggest that this method could be used to investigate a wide variety of other analytes that are dilute in solution.
solutions is significantly lower. Ni3N, a material whose surface has a special affinity for oxygen and water molecules, is a relatively efficient catalyst in alkaline solutions. However, this material undergoes corrosion and passivation in alkaline environments, making it impractical for long-term use. Zhou et al. (DOI: 10.1021/acsnano.7b08724) sought to overcome these issues by substantially boosting the durability of the Ni3N surface with carbon. The researchers created carbonreinforced Ni3N by dipping Ni(OH)2 in a carbon quantum dot solution, then heating the recovered solids to convert the Ni(OH)2 to Ni3N. The resulting material showed enhanced catalytic activity, with an overpotential of 69 mV at a current density of 10 mA cm−2 in a 1 M KOH aqueous solution, significantly lower than that of a Pt electrode at the same conditions. The carbon coat also protected the interior of the Ni3N from oxidation/hydroxylation over hours of continuous use. The authors suggest that this design could offer a way to produce robust and durable catalysts for hydrogen evolution while avoiding the expense and rarity of precious metals.
A TARGETED HIT ON PARKINSON’S DISEASE Parkinson’s disease (PD) is characterized by degeneration of dopaminergic neurons in the substantia nigra (SN), resulting in motor dysfunction and other nonmotor impairments. Some studies have observed iron overload in affected SN cells. Because excess iron deposition can lead to oxidative stress-related damage and necrosis, iron chelation has been suggested as a potential treatment for PD, with deferoxamine (DFO) as the most effective chelator with the most favorable toxicity profile. However, this drug poorly penetrates the blood−brain barrier and has serious side effects at the high doses required for treatment. To address these issues, You et al. (DOI: 10.1021/ acsnano.7b08172) packaged DFO in polymer nanocarriers conjugated to rabies virus glycoprotein 29, a protein that can effectively cross the blood−brain barrier and specifically binds to a receptor that is widely distributed on the extracellular surfaces of brain microvascular endothelial cells as well as neurons. Experiments show that these nanocarriers were readily internalized by brain capillary endothelial cells and neurons and could penetrate a blood−brain barrier in vitro model with significantly less cellular
MORE RESILIENT HYDROGEN EVOLUTION Hydrogen evolution has attracted increasing attention over the past several years as a promising source of clean and renewable fuel. Although electrochemical water splitting has been well studied, finding efficient and economical materials to catalyze this reaction has remained a challenge. Currently, the most effective catalysts are platinum-based; however, platinum cannot be used extensively due to its low abundance and high cost. Transition-metal-based catalysts have shown promise in replacing platinum-based ones, but their efficiency in alkaline © 2018 American Chemical Society
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Published: May 22, 2018 4077
DOI: 10.1021/acsnano.8b03422 ACS Nano 2018, 12, 4077−4080
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GETTING SINGLE NUCLEOTIDE POLYMORPHISM DETECTION LOCKED DOWN Single nucleotide polymorphisms (SNPs), or single nucleotides that differ between individuals at specific sites in the genome, have arisen as important biomarkers for diagnostics and species identification. Although several technologies have been developed to detect SNPs in clinical settings, new approaches with greater resolution, accuracy, and speed are in high demand. One approach that has attracted significant attention uses locked nucleic acids (LNAs), a class of artificial RNA-mimicking nucleotides. A “locked” ribose ring on LNAs can increase the double strands’ thermal stability when hybridized to a complementary DNA or RNA, turning them into a high-performance probe for SNPs and other hybridization-based applications. However, designing LNAs for this purpose has thus far been a complicated, laborious, and expensive process, requiring the incorporation of at least three LNA nucleotides per probe. Tian et al. (DOI: 10.1021/acsnano.8b01198) improved the sensitivity of LNA-based SNP detection and showed that it is possible to use only a single LNA nucleotide by combining this method with a nanopore, a sensing technology that can distinguish differences in nucleic acids at the single nucleotide level. By designing probes with just a single LNA nucleotide, the researchers found elongation of the unzipping time of fully matched duplexes as well as shortened unzipping time of single-matched duplexes compared to pure DNA probes, magnifying the differences between target and nontarget sequences. This approach enabled detection of SNPs to detect a deadly strain of E. coli as well as two different driver mutations for cancer. The authors suggest that this method could be generalized for various applications that need rapid and accurate identification of single-nucleotide variations.
toxicity compared to the free drug. When loaded with DFO, these complexes effectively removed intracellular iron both in vitro and in vivo. In a mouse model of PD, functional deficits reversed after treatment with the targeted, loaded nanoparticles. The authors suggest that this nanoformulation could hold great promise for delivering DFO into the brain and realizing iron chelation as a viable treatment for PD.
ATTACKING GLIOMA THROUGH THE BLOOD−BRAIN BARRIER The blood−brain barrier (BBB) is critical for maintaining homeostasis of the central nervous system and preventing entry of potential neurotoxins into the brain. However, it is also a formidable obstacle to delivering drugs to the brain. The selective permeability of the BBB blocks entry of both large molecules and the majority of antitumor drugs, hindering effective treatment of many brain-related diseases. One potential strategy for getting around this hurdle is to target endogenous receptor-mediated transport systems, such as transferrin receptor 1, which is highly expressed on both the vascular endothelial cells of the brain capillaries that make up the BBB and on brain tumor tissues. Taking advantage of this factor, Fan et al. (DOI: 10.1021/ acsnano.7b06969) designed nanocarriers made of human H-ferritin, a protein whose principal point of entry is transferrin receptor 1. In a series of experiments, the researchers showed that these nanocarriers successfully cross the BBB both in cultured cells and in vivo in mouse models, collecting in glioma tumor cells. When the researchers loaded these nanocarriers with doxycycline, a drug commonly used to treat gliomas, they effectively killed tumor cells in an orthotopic glioma mouse model, significantly extending survival time. This treatment appeared to have no significant toxicity, suggesting an excellent biosafety profile. These results suggest that human H-ferritin could serve as an ideal nanocarrier to treat gliomas and potentially a broad range of other central nervous system diseases.
BUCKLE UP FOR THREE-DIMENSIONAL SILICON ELECTRONIC SYSTEMS Numerous three-dimensional (3D) complex mesostructures exist in nature, where overall function is intimately tied to architectural layouts. The ability to harness 3D layouts in electronics could powerfully influence a variety of applications, including microelectronic devices, optoelectronic components, energy storage systems, biomedical sensors, and microsurgical tools. Although techniques such as 3D printing, multiphoton lithography, guided assembly, and origami/kirigami offer enhanced capabilities in this area, few combine the desired design versatility and compatibility with the two-dimensional (2D) device structures and active materials currently dominating microsystems technologies. Seeking a way to produce 3D electronic systems from 2D components, Kim et al. (DOI: 10.1021/acsnano.8b00180) developed a technique that uses a compressive buckling process. The researchers spin-cast a layer of poly(methyl methacrylate) and a layer of polyimide on a silicon wafer. They then fabricated a 2D precursor circuit onto these polymers and released the circuit onto a polydimethylsiloxane stamp, which they applied to an 4078
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pivotal for pathogenesis, such as hemagglutinin, a protein on the influenza virus surface that needs to bind to sialic acid on host epithelial cells for infection to occur. Thus, synthesizing multivalent ligands that can compete with and inhibit infectious ones has become a target for pharmaceutical research. Typical synthetic multivalent ligands have rigid cores of varying chemical composition with ligands attached by polymer linkers. To optimize the design of these structures, researchers must optimize several parameters, including the size and shape of the core, the linker length, and the synthetic procedures to construct these ligands. Toward this end, Liese and Netz (DOI: 10.1021/ acsnano.7b08479) developed a molecular model for the binding affinity of synthetic multivalent ligands onto multivalent receptors. They examined ligands against three moieties, with varying numbers of attached monovalent ligands (n): influenza viral hemagglutinin (n = 3), cholera toxin (n = 5), and anthrax receptor (n = 7). Their model, which closely matches experimental data, shows that the angular steric restriction between ligand unit and linker polymer is a key ingredient of multivalent enhancement. In addition, their model suggests that the highest gain in binding affinity is achieved with a ligand core size that matches the receptor size, and that the ideal linker length is slightly longer than the distance between receptor and core. Finally, the model indicates that multivalent ligands can only outperform monovalent ones when monovalent ligand affinity exceeds a core-size dependent threshold value. These findings, the authors suggest, could help steer multivalent drug design.
elastomer substrate. When the prestrain of this substrate was released, the 2D system was geometrically transformed into a 3D system by a process of guided delamination and buckling of the nonbonded regions. The researchers used this technique to create architectures ranging from interconnected bridges and coils to extended chiral structures, each embedded with n-channel Si nanomembrane metal-oxide-semiconductor field-effect transistors (MOSFETs), Si nanomembrane diodes, or p-channel Si MOSFETs. The authors suggest that this strategy could prove useful for applications in energy storage, photovoltaics, optoelectronics, and more.
MAKING A MENISCUS THAT IS FIT TO PRINT Although three-dimensional (3D) printing technology has had enormous impact on many fields, most of the conventional techniques encompassed by this technology, such as fused deposition modeling and stereolithography, suffer from serious drawbacks. These obstacles include relatively low spatial resolution and productivity and limited material selection, which critically limit their practical applications. One way to address these issues is by using a nanopipet. One working mechanism exploited in nanopipetassisted 3D printing uses the formation of a femtoliter-sized meniscus formed at the pipet−substrate gap in air. However, the production of this meniscus has relied on either the physical contact of a fragile glass nanopipet with the substrate or integrated positional feedback based on detecting an electrochemical current across the experimental system. Both approaches have proven challenging to implement reliably. Chen et al. (DOI: 10.1021/acsnano.8b00706) offer a way around this hurdle through a new noncontact, programmable method that produces a femtoliter liquid meniscus that can be used for parallel 3D nanoprinting. By precisely controlling the micrometer-scale distance between a polymer ink-filled nanopipet and a silicon substrate, the researchers were able to generate an electrostatic force that prompts this meniscus to form. The meniscus then facilitates the delivery of materials in a confined region. Guiding the meniscus in three dimensions while the ink rapidly solidifies enables the creation of 3D nanostructures with programmed shapes. The researchers show that this technique can be used with a multibarrel pipet to achieve parallel printing of clustered nanowires with precise placement. The authors suggest that this technique could advance productivity in nanoscale 3D printing.
IMAGING NANOPARTICLES THROUGH THE AGGREGATES Plasmonic nanoparticles such as gold nanorods have received growing attention as biolabeling probes due to their numerous useful qualities, such as high photostability and large extinction cross sections that help them provide high spatial and temporal resolution images. Imaging these materials individually could offer useful ways to track them as they deliver cancer drugs, RNA, DNA, and ferritin-encapsulated nanodrugs. However, imaging single nanoparticles with optical microscopes has proven challenging thus far due to factors including coupling of nearby plasmonic nanoparticles. Although single-molecule studies have been accomplished using a variety of techniques, it remains difficult to separate individual nanoparticles at their aggregates. Chakkarapani et al. (DOI: 10.1021/acsnano.8b00025) report a way to superlocalize gold nanorods within aggregates, even inside the “noisy” environment of cells, by coupling two microscopy techniques. The researchers paired a dove-type prism-based light sheet microscope with a polarization-based differential interference contrast microscope. Bringing these two together into an integrated light sheet super-resolution microscopy system, they used asymmetric light scattering of a nanorod to trigger signals based on the polarizer angle. By turning the polarizer, the
A MODEL FOR MULTIVALENCY Multivalent interactions, in which bonding occurs simultaneously between several monovalent ligands and receptor units, are 4079
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researchers were able to achieve controlled photoswitching. They achieved three-dimensional subdiffraction-limited superresolution images by superlocalization of the scattering signals, made possible by the gold nanorods’ anisotropic optical properties. Varying the polarizer enabled resolution of individual nanorods, even in aggregated locations and in the inhomogeneous interior of cells. The authors suggest that this microscopy technique could be widely applicable in optics, biomedicine, and materials science.
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