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CUTTING THE FAT WITH NANOCELLULOSE Engineered nanocomponents are increasingly being added or applied to foods to boost quality, safety, and nutrition. In particular, nanocellulose has been used to boost fiber content in foods, to stabilize emulsions and foams, to retain moisture, and to improve appearance and sensory appeal. However, its potential to modify digestion had not been investigated. DeLoid et al. (DOI: 10.1021/acsnano.8b03074) examined nanocellulose derived from natural wood fiber in a series of experiments to determine its effects on fat digestion and absorption. Using heavy cream as a model high-fat food, the researchers added 0.75% w/w nanocellulose with a mean fibril diameter of 50 nm. In the simulated gastrointestinal tract, adding nanocellulose cut the hydrolysis of free fatty acids from triglycerides by nearly half, as quantified by pH-Stat titration. In an in vitro cellular model of the intestinal epithelium, nanocellulose cut translocation of triglycerides by half and cut translocation of free fatty acids by a third. In an in vivo rat model, postprandial rise in serum triglycerides was reduced by 36% when 1% w/w nanocellulose was added to the food. Scanning electron microscopy images of digesta suggest two primary mechanisms for this effect: coalescence of fat droplets on the nanocellulose fibers, which reduces the surface area available for lipase binding, and a sequestration of bile salts, which leads to impaired solubilization of lipid digestion products. These findings suggest that nanocellulose could be a useful food additive to assist in weight loss and to manage obesity.
effectively across the intestinal epithelium. Using curcumin as a model therapeutic with low oral bioavailability, the researchers filled an enteric-coated gelatin capsule with this drug and several components: a powdered mixture of an acid initiator, a foaming agent, and a surfactant. When the acid initiator hydrolyzes in water, it reacts with the foaming agent to generate a bubbly CO2 stabilized by the surfactant. Transforming first into a doublelayer assembly and then into a micellar nanoemulsion as the bubbles burst, these assemblies incorporate curcumin, readily transporting it across the membranes of microfold cells (M cells) in the small intestine. Tests with in vivo models show that this nanocarrier enables curcumin to be transported into pancreatic tissues through the mesenteric lymphatic system, where it effectively treated acute pancreatitis in an animal model. The authors suggest that this system could be used for other types of poorly water-soluble drugs, making oral delivery a favorable option.
WATER ON SOLIDS: TAKING A CLOSER LOOK The water−solid interface plays an important role in a wide array of phenomena, including corrosion, catalysis, electrochemistry, and life activities. One step in understanding this interface is to elucidate the microscopic nature of water clusters at their initial state of nucleating onto solid surfaces. The molecular structure of water clusters on a surface is determined by hydrogenbonding interactions between adjacent water molecules and bonding forces between water molecules and the substrate. Although water−substrate bonds are normally stronger than hydrogen bonds on reactive metal surfaces, the bonding forces between water molecules and substrate are generally weaker on noble metals, enabling van der Waals dispersion forces to take a greater role. Sorting out the balance between these two forces has been a challenge for water science due to long-standing difficulties in imaging water clusters on nonreactive surfaces. Dong et al. (DOI: 10.1021/acsnano.8b02264) overcome this challenge by combining the use of a low-temperature scanning tunneling microscope with first-principles calculations. With a water-molecule- or hydroxyl-group-terminated probe tip, the researchers were able to image water clusters on Au(111) surfaces with ultrahigh resolution, distinguishing the adsorption site and height of each molecule in the clusters deterministically. Their findings show that for trimer, tetramer, and pentamer
TRANSFORMERS: MORE THAN MEETS THE MOUTH Taking medications orally is the most comfortable and convenient route for administration. The most critical ratelimiting step for achieving therapeutic concentrations of ingested medications is when they dissolve in the intestines. However, many small-molecule drugs are poorly soluble in water and form insoluble aggregates in bodily fluids, reducing their oral bioavailability. Despite decades of effort, improving the oral absorption of drugs that have poor oral bioavailability remains elusive for pharmaceutical chemistry. To address this challenge, Chuang et al. (DOI: 10.1021/ acsnano.8b00470) developed a “Transformers”-like nanocarrier system that combines several ingredients to form nanoemulsions of a poorly water-soluble molecule, enabling it to be absorbed © 2018 American Chemical Society
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Published: July 24, 2018 6347
DOI: 10.1021/acsnano.8b05310 ACS Nano 2018, 12, 6347−6350
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Cite This: ACS Nano 2018, 12, 6347−6350
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MISLEADING GLOW OF FLUORESCENT BIODISTRIBUTION STUDIES Thousands of studies have relied on fluorescence-based wholebody imaging to evaluate nanoparticle distribution in small animals. This method, which generally involves encapsulating or conjugating organic near-infrared fluorophores in or on nanoparticles, offers time-, labor-, and cost-effective, noninvasive, simple detection of dispersal. And because this method can visualize spatiotemporal distribution of nanoparticles in the same animal, it reduces intersubject variability and decreases the number of required subjects. The underlying assumption behind this method is that the fluorescence label represents nanoparticles, with fluorescence increasing with the number of nanoparticles or the amount of labeling dye accumulating in the region of interest. However, Meng et al. (DOI: 10.1021/acsnano.8b02881) show that this assumption is not always correct, with the opposite scenario sometimes in play. The researchers loaded poly(lactic-co-glycolic acid) nanoparticles, either terminated with folate or without, with two different concentrations of the commonly used fluorescent dye 1,1′-dioctadecyl-3,3,3′,3′-tetramethylindotricarbocyanine iodide (DiR). They then compared the distribution of fluorescence signals in a mouse model of folate-receptor-expressing tumor by near-infrared fluorescence whole-body imaging. Surprisingly, they found that the fluorescence distribution patterns differed far more dramatically with the dye-loading content than with the surface ligand. For example, animals with less DiR showed high fluorescence in the liver, and those with more DiR showed higher fluorescence in the tumor. Further analysis showed that a variety of factors, including fluorescence quenching, dequenching, and signal saturation, are responsible for these misleading results. The authors suggest that researchers should mitigate these factors to avoid conflicting or deceptive misinterpretations in future studies.
groupings, the clusters present buckled configurations, but for hexamers, the configuration is unambiguously coplanar, even after probe tip manipulation. Using van der Waals corrections in density functional theory calculations gave excellent agreement with these experiments. The authors suggest that these findings facilitate understanding of the competition and subtle balance between water−water and water−solid interactions.
LESS IS MORE FOR CANCER NANOVACCINE To increase the immunogenicity of purified antigens, vaccine science has traditionally relied on the use of adjuvants. For example, aluminum salt has been used as an adjuvant in several vaccines for nearly a century. However, this strategy has had limited success in eliciting T-cell responses, which are critical for mounting antitumor defenses. One way to solve this problem is by using nanocarriers to combine adjuvant and antigen, a strategy that mimics pathogens such as viruses. However, it has been difficult to develop nanocarriers that incorporate abundant adjuvants, such as liposomes or poly(lactic-co-glycolic acid), as well as nanocarriers that enable multicopy display of antigens, rather than entrapping them. Wang et al. (DOI: 10.1021/acsnano.8b00558) get around these difficulties by developing a minimalist nanovaccine derived from nearly whole antigens. The researchers allowed ovalbumin antigens and CpG agonists to self-assemble into a compact nanovaccine by moderately denaturing the ovalbumin protein, exposing free thiols that stabilize these components into a disulfide network. This strategy resulted in superhigh antigen packing of 97% that incorporated the CpG “danger signal” without the assistance of any exterior nanocarriers. Evidence from transmission electron microscopy suggests that approximately 500 antigen particles were packed into each 50 nm nanoparticle. In a murine model, this nanovaccine protected about 70% of the animals from tumorigenesis from B16-OVA melanoma. Mechanistic studies show that this tumor inhibition was the result of nanovaccine-induced cytotoxic T lymphocytes. The authors suggest that this strategy could be used to produce a variety of compact nanovaccines for clinical use.
CLEAR FUTURE FOR GRAPHENE GLASS AND CHOLESTERIC LIQUID CRYSTALS Cholesteric liquid crystals (ChLCs) have potential in a variety of fields, such as intelligent laser protection, next-generation ultrafast reflective displays, and energy-saving smart windows. To realize these applications, the orientation of ChLCs must be highly controlled. Because their alignment depends on the nature of the substrate, researchers have achieved this end by mechanically rubbing a polymer layer onto the target surface. However, this method has drawbacks, including introducing dust particles and creating electrostatic charges. Recent research has suggested that liquid crystal (LC) molecules can align along the crystalline orientation of chemical-vapor-deposition-derived graphene as a consequence of relatively strong epitaxial interactions between LC molecules 6348
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and graphene. Capitalizing on this phenomenon, Wang et al. (DOI: 10.1021/acsnano.8b01773) relied on graphene on glass substrates to align overcoated ChLC molecules, generating a multidomain structure that can provide a wider viewing angle for graphene-glass-based ChLC devices. The researchers started by growing high-quality graphene directly on solid quartz glass. Over this substrate, they fabricated LC cells. Polarized optical microscope characterization revealed that the ChLCs assembled into oriented multidomain structures. Unexpectedly, these structures introduced a multidimensional aspect to reflected light, leading to a wider viewing angle, particularly in the infrared region. In addition, relying on the electrical properties of graphene, the researchers were able to switch this material reversibly between highly transparent and strong light-scattering states by applying a low electrical field. The authors suggest that this technology could be useful in an array of energy- and safetyrelated applications.
FIGHTING VIRAL INFECTION, THE NANOGEL WAY Antiviral drugs currently in use mainly target specific viral proteins in order to interrupt the replication cycle, which gives the immune system extra time to control or to clear the infection. However, these drugs are specific for select viruses that represent just a narrow subset of viruses’ high diversity. Targeting early steps of infection, such as the entry of viral particles into host cells, could offer a broader inhibition approach. For example, the initial contact of several unrelated viruses, including herpesviruses, arteriviruses, papillomaviruses, and flaviviruses, begins with attachment to heparan sulfate (HS) proteoglycans on the cell surface. Inhibiting this step could offer a different antiviral approach. Toward this end, Dey et al. (DOI: 10.1021/acsnano. 8b01616) report nanogels (NGs) that mimic and compete with cellular HS, blocking viral infection at the earliest stages. The researchers designed two types of NGs based on dendritic polyglycerol sulfate, assembled through an inverse precipitation based on a bio-orthogonal click reaction. They tuned the flexibility of these constructs, testing both rigid and flexible NGs against viral activity. Their experiments show that these NGs are potent inhibitors of herpes simplex virus 1 and porcine reproductive and respiratory syndrome virus, significantly preventing infection in cells incubated with either virus and nanogel. The flexible NG was more potent than the rigid one, displaying stronger inhibition with lower concentration. Mechanistic studies show that this inhibition works through interaction with the virus, which prevents attachment to cells. In the absence of virus, these nanogels enter cells through clathrinmediated endocytosis, with negligible toxicity. The authors suggest that this strategy could be used broadly to inhibit unrelated viral species.
DUAL-MODE METASURFACE SEES THE LIGHT One way to realize flat optical devices is through metasurfaces consisting of ultrathin subwavelength antennas. To achieve the desired functionality, these antennas must be designed to enable precise control of the optical properties of incident light. Much of the research in this area has focused on wavefront manipulation because of its wide array of applications, including beam-steering devices, lenses, holograms, skin cloaks, and other optical components. However, metasurfaces can be further improved by incorporating multifunctionality. Although metasurfaces have been designed to control either phase or spectral responses of subwavelength structures, none have been reported that can simultaneously achieve both. Yoon et al. (DOI: 10.1021/acsnano.8b01344) accomplish this feat, describing a metasurface that produces not only conventional metaholograms under single-wavelength coherent light but also reflective displays under white light illumination. The researchers designed this surface using two kinds of unit cells consisting of double dielectric nanoantennas constructed from parallel nanorods. Each unit cell had the same crosspolarization transmittance but different reflection spectra. The orientations of these nanoantennas determined the phase distribution of single-wavelength coherent light, while their sizes determined the reflection spectrum under white light illumination. Tests with multiple metasurfaces showed that the same metasurface could display different images in either transmission or reflection mode depending on the type of light shined on it. There was no cross-talk between the two images, enabling each to be hidden while the other one was on view. The authors suggest that this “crypto-display” could find use in security techniques.
OPENING THE GATEWAY TO EXCITON PROCESSING AND SIGNALING Many areas of engineering and science rely on gates to regulate the movement of energy, mass, or charge. These include fieldeffect transistors for computing, relays for larger electronics, and valves for modulating fluid flow in civil engineering. Being able to control the direction and migration of excitons could enable the development of nanoscopic devices in spectroscopy, 6349
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microscopy, photocatalysis, and sensing. Although several schemes have been proposed for excitonic gating designs, including logic devices based on DNA nanotechnology, incident light to induce molecular rearrangement, and specific chromophores excited into an optically inaccessible state, each of these designs has significant drawbacks. Sawaya et al. (DOI: 10.1021/acsnano.8b00584) proposed a design for an elementary excitonic gate that uses multiple excited states to control the flow of excitons in organic molecules, enabling a host of benefits not possible in previous designs. Their strategy operates in the incoherent Förster resonance energy transfer (FRET) regime, using organic fluorophores arranged by DNA origami in a downhill energy cascade. These individual groupings, which enable excitation migration via the second excited singlet state of the gate molecule, can be further arranged into multiples that function as logic gates, with AND, OR, and NOT functions. These theoretical gate molecules have a variety of useful features, including picosecond time scale actuation, amplification/gain behavior, and a lack of molecular rearrangement, only a subset of which are present in previous exciton switching schemes. The authors suggest that a careful choice of gate molecules and placement could bring these simple but sophisticated hypothetical gates to fruition.
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