DNA RELEASE FROM NANOPARTICLES: SEEING THE LIGHT For precise spatial and temporal release of drugs and genetic material, a significant body of research has focused on developing methods that use externally applied triggers such as magnetic and electric fields, ultrasound, and light. In one method, thiolated DNA bound to near-infrared absorbing gold nanoparticles is released from the nanoparticle surface with resonant illumination. Some studies exploring this method have used continuous wave (CW) lasers to dehybridize double-stranded DNA (dsDNA), releasing single strands while keeping the complementary strands tethered. Others have used pulsed lasers either to dehybridize double-stranded DNA or to break the gold−thiol bond between the DNA molecule and nanoparticle, releasing entire double strands. While both schemes have been demonstrated multiple times, the mechanism behind lighttriggered DNA release remains uncertain. To understand this process, Goodman et al. (DOI: 10.1021/ acsnano.6b06510) examined both CW and pulsed-lighttriggered DNA release from gold nanoshells functionalized with partially thiolated dsDNA. Comparing CW laser-induced DNA release to a thermal release profile they developed by heating the functionalized nanoparticles at 5 °C increments, the researchers found numerous similarities. In this case, DNA release ultimately depends on samples rising above the DNA melting temperature as well as nanoparticle concentration, suggesting that thermal effects dominate. In contrast, a femtosecond pulsed laser at low average powers did not raise the sample temperature, suggesting that DNA release occurs through a hot-electron transfer process, breaking the gold−thiol bond. The authors suggest that these results promote pulsedlaser-induced DNA release as a promising strategy for therapeutic DNA release in vivo, where avoiding bulk heating is key.
metallic counterparts. Directly growing s-SWNTs remains a greater challenge. Researchers have had some success in inhibiting the growth of metallic SWNTs (m-SWNTs) by employing water vapor, methanol, oxygen, or UV light during chemical vapor deposition (CVD) to create an oxidative environment. However, the highest reported content of sSWNTs produced by this method is ∼97%, still far below the purity requirements of many applications. Testing another strategy, Yang et al. (DOI: 10.1021/ acsnano.6b06890) relied on catalysts whose structure was selectively modified using water vapor during the crystallization process. The researchers introduced water vapor to H2 during the synthesis of W6Co7 catalysts, an addition that increased the abundance of (1 0 10) planes. Using these catalysts for CVD growth of s-SWNTs produced a result with 99% purity, 97% of which was composed of nanotubes with (14,4) chirality. To improve the purity of the s-SWNTs, the researchers then treated as-grown samples with water vapor at 550 °C, which oxidizes mSWNTs. Tests showed that the abundance of s-SWNTs increased to 99.8%, with purity of (14,4) tubes increasing to 98.6%. Back-gated field-effect transistors fabricated using the purified tubes showed typical semiconducting performance. The authors suggest that this method is a powerful pathway toward directly growing pure s-SWNTs for the next generation of highend nanoelectronics.
BREATH OF FRESH AIR FOR DISEASE CLASSIFICATION A variety of studies have shown that changes in the body’s metabolism can alter expelled volatile organic compounds (VOCs), signaling the presence of disease. The most clinically relevant way to detect these changes is through exhaled breath. However, although current methods have the potential to identify disease, they cannot classify it into possible conditions. Some research has explored recognizing specific diseases through nanotechnology approaches that selectively detect preidentified VOCs. However, this approach severely limits the selection of diseases that can be identified using targeted sensors. In a recent study, Nakhleh et al. (DOI: 10.1021/acsnano. 6b04930) report an artificially intelligent nanoarray that can both detect and discriminate between 17 different disease conditions using exhaled breath. The array is based on chemiresistive layers of molecularly modified gold nanoparticles and a random network of organically functionalized single-wall carbon nanotubes. The inorganic materials in these sensors provided electrical conductivity, while the organic layer functioned as a
LIKE WATER FOR SEMICONDUCTING CARBON NANOTUBES Structurally uniform semiconducting single-walled carbon nanotubes (s-SWNTs)with their inherently identical band structureshave been sought after for high-end nanoelectronic applications. To this end, researchers have developed a variety of methods for purifying s-SWNTs from mixtures containing their © 2017 American Chemical Society
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sensing element for adsorbed VOCs. The researchers tested this tool on breath samples from 1,404 subjects from five different countries. This population included 591 healthy controls and 813 patients diagnosed with one of 17 different diseases, including various cancers, inflammatory diseases, neurological diseases, and others. Results showed that changes to the electrical resistance of the sensors provided a unique “breathprint” for each of the 17 diseases. These results were validated using mass spectrometry, which showed 13 exhaled chemical species associated with these diseases in combinations that differed for each individual condition. The authors suggest that this work provides a starting point for creating an affordable, easy-to-use, inexpensive, and miniaturized tool to monitor health using exhaled breath.
DNA’S AMAZING PROTEIN POLYMER DREAMCOAT DNA-based nanotechnologies such as DNA origami, singlemolecule DNA imaging, and nanopore sensing often require precise control of this genetic molecule’s physical and chemical properties. Altering solution conditions can offer some degree of control over these factors but rarely provides the requirements necessary for these applications. One way to modify the properties of individual DNA molecules is to add nonelectrostatic DNA binders. Recently, researchers designed, produced, and characterized a recombinant, protein-based polymer that protects against enzymatic degradation without making DNA completely inaccessible to sequence-specific binders. Although this polymer was highly effective for coating linear double-stranded DNA (dsDNA), further evaluation showed that it caused undesirable distortion of DNA origami structures. In a recent study, the same group of Hernandez-Garcia et al. (DOI: 10.1021/acsnano.6b05938) described a protein polymer that can coat both individual DNA molecules as well as folded origami structures without causing distortion. The coating agent, called C8−BSso7d, was constructed by combining a nonelectrostatic DNA binding domain derived from archaea with a long hydrophilic random coil polypeptide, which provides solubility through the formation of polymer brushes around the DNA structures. Tests showed that C8−BSso7d, which is produced recombinantly in yeast, can effectively coat and increase the stiffness of one-dimensional strands of DNA, including linear dsDNA, supercoiled dsDNA, and circular singlestranded DNA (ssDNA), as well as two-dimensional rectangular DNA origami structures. Besides changing these DNA templates’ mechanical properties, the coating also offered moderate protection against nucleases. The authors suggest that this engineered protein hold promise for applications including creating DNA−protein hybrid networks or transfection of DNA nanostructures into cells.
CRYSTALLIZING UNDERSTANDING OF PROGRAMMABLE ATOM EQUIVALENTS Nanoparticles functionalized with a dense monolayer of oligonucleotides can form ordered superlattices with lattice parameters and crystallographic symmetries that can be tuned by changing the properties of the attached DNA. Although these components, known as programmable atom equivalents (PAE), show many crystallization behaviors that mimic those of atomic systems, using them to synthesize multilayer single crystals of defined size, shape, and orientation remains challenging. Several previous studies have suggested lattice mismatch as the prevailing limiting factor for multilayer assembly. However, a complex array of interlinked factors can affect three-dimensional growth of PAE thin films. In a recent study, Wang et al. (DOI: 10.1021/acsnano. 6b06584) delve into these variables to understand and to promote epitaxial growth of PAE thin films better. Their tests show that a templated substrate, crafted by electron-beam lithography, plays a strong role in promoting epitaxy, but this driving force is only relevant for a few layers when lattices are assembled under nonequilibrium conditions. Like their atomic counterparts, PAE thin films became crystalline and epitaxial upon annealing at just below the melting temperature of the superlattice. However, as the layer number increased beyond 5, samples became crystalline but not epitaxial. The highest degree of ordering occurred when each layer of PAEs was deposited at an optimized growth temperature that was 4° lower than the superlattice melting temperature. By using DNA intercalators after assembly, bonds between PAEs were strengthened to prevent reorganization during subsequent cycles of growth, increasing epitaxy even in films with many layers. The authors suggest that these findings lay the groundwork for creating functional device architectures from crystalline nanoparticle networks.
GETTING CLUSTERED REGULARLY INTERSPACED SHORT PALINDROMIC REPEATS INTO CELLS Clustered regularly interspaced short palindromic repeats (CRISPR) systems, derived from RNA-based immune components that archaea and bacteria use to protect themselves from exogenous nucleic acids, have recently soared in popularity as 9
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composed of different ratios of these building blocks, the team found that the fluorescent supramolecular nanoparticle (FSNP) with the best performance was 670 nm in diameter. After crosslinking these particles together into various sizes, tests showed a size-dependent effect on retention times, with the largest crosslinked FSNPs retained for 84 days in the skin of animal models. Additional experiments showed no evidence of inflammatory response after tattooing. The authors suggest that these new inks could offer a short-term solution for medical tattooing.
gene-editing tools. In particular, the CRISPR-associated protein 9 (Cas9) holds promise for biomedical research. Currently, this system is usually delivered into cells through a plasmid encoding Cas9 nuclease and a single guide RNA (sgRNA) sequence. However, the large size of this complex makes effective delivery a challenge. Although delivery has been accomplished successfully in vitro through nucleofection, electroporation, and lipofectamine, these approaches limit in vivo application. In a recent study, Li et al. (DOI: 10.1021/acsnano.6b04261) detail an artificial virus they developed that can effectively deliver the CRISPR-Cas9 system. This artificial virus was constructed of a core of fluorinated polymer that binds with the CRISPR-Cas9 system combined with a multifunctional polymer shell that facilitates cellular uptake and targets the nucleus. Tests showed that this vehicle could efficiently load the CRISPR-Cas9 system, accelerate endosomal escape, and penetrate the nucleus without an additional nuclear-localization signal. Using an ovarian cancer oncogene as a model, further experiments showed that the artificial virus was more effective at transfecting than SuperFect, Lipofectamine 2000, and Lipofectamine 3000, with better targeted gene disruption efficacy than Lipofectamine 3000. Additionally, this carrier induced minimal side effects in an animal model, suggesting its safety for in vivo applications. The authors suggest that this artificial virus could offer an effective delivery system for the CRISPR-Cas9 system or other functional nucleic acids.
SPRAYING ON THE STRAIGHT AND NARROW Being able to align molecules and nanoscale objects with anisotropic physical properties is pivotal for taking advantage of their unique characteristics. In thin films, these components are typically oriented using mechanical, electrical, or magnetic external fields, by templating, or by physical methods such as stretching or rubbing a substrate covered with anisotropic particles. However, each of these methods has inherent drawbacks that significantly limit their use. These problems underline the need to develop new and better ways to align anisotropic materials. To this end, Blell et al. (DOI: 10.1021/acsnano.6b04191) report a simple and efficient way to orient nanoscale anisotropic objects in layer-by-layer assembled films through a method called grazing incidence spraying (GIS). Rather than spraying against a receiving surface at a normal (90°) angle, which produces films with homogeneous in-plane orientation, GIS requires spraying at more grazing angles. This process results in a macroscopic directional surface flow of liquid on the receiving surface that leads to films with substantial in-plane anisotropy. Using this method on cellulose nanofibrils, the researchers produced optically bifringent films over large surface areas. Grazing incidence spraying caused these materials to orient parallel to the spraying direction, with factors including direction and inclination of the spray jet and the size, speed, and density of the droplets affecting ordering. The authors suggest that this method could be used over areas as large as postcards or to prepare anisotropic multimaterials with complex compositions.
MAKING TATTOOS A SHORT-TERM COMMITMENT As sun exposure in the United States has increased in the past several years, so has the incidence of nonmelanoma skin cancers. Over 3.3 million cases of these conditions are diagnosed each year, rising at a faster rate than breast, prostate, lung, and colon cancers combined. Because the interval between diagnosis and surgical treatment can be up to three months, a time in which the lesion can change to become nearly invisible, the cancerous site is often marked with a tattoo composed of either conventional carbon graphite and India ink or fluorescent particles that are visualized under UV light. Both types of markings have drawbacks; conventional pigments are cosmetically unappealing and can be mistaken for a melanocytic lesion, and either type of tattoo can cause an uncomfortable local inflammatory response and necessitate laser or surgical treatment for removal. In a recent study, Choi et al. (DOI: 10.1021/acsnano. 6b06200) detail a method for creating “finite” tattoos that last only about three months and avoid these shortcomings. The researchers used supramolecular nanoparticles to encapsulate a fluorescent conjugated polymer. Using a combinatorial library 10
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PUTTING A BIG RING ON IT Significant recent research has focused on fragments of carbon allotropes, including buckybowls, graphene nanoribbons, nanosheets, and conjugated macrocycles. These materials have unique and potentially useful electronic and optical properties, and their shape-persistent structures hold promise as parts of molecular motors and molecular machines or for nanostructuring surfaces. Thus, far, many conjugated macrocycles have been synthesized in solution, which requires the addition of bulky side chains to increase solubility. Because these spacious substituents persist in the final product, adversely affecting useful properties, being able to synthesize conjugated macrocycles in the solid state without these side chains would be a welcome advance. In a recent study, Chen et al. (DOI: 10.1021/acsnano. 6b05709) accomplish this goal, creating large oligophenylene macrocycles that they call honeycombenes due to their hexagonal shape. These macrocycles were synthesized by reacting six molecules of 4,4i⁗-dibromo-meta-quinquephenyl on a Ag(111) single-crystal surface, breaking their C−Br bonds. In addition to the large macrocycles composed of 30 phenyl rings, side products include strained macrocycles with square, pentagonal, and heptagonal shapes. Analysis of the honeycombenes with scanning tunneling microscopy, density functional theory (DFT), and other tools suggests that these structures act as molecular quantum corrals on the Ag(111) surface, leading to the confinement of surface state electrons inside the central cavity. Tunneling spectroscopy suggests conjugation within the planar rings. While adsorbed molecules appear to adopt a planar conformation, DFT calculations suggest a variety of other conformations for free molecules. With a diameter of 4.0 nm, these honeycombenes, the authors say, represent the largest shape-persistent, fully conjugated, and unsubstituted macrocycle known to date.
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