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NEEDLING AWAY AT CANCER Vaccines have proven to be increasingly powerful in fighting and preventing cancer. For vaccines to be effective, the efficient delivery of antigens and immunomodulators to lymph nodes is critical. There, these agents aid in the maturation and activation processes for antigen presenting cells (APCs). Microneedles offer an attractive way to deliver vaccines through the skin, avoiding unnecessary pain while also accessing resident APCs in the skin. Among various types of microneedles, those that dissolve offer advantages such as ease of preparation and improved safety. However, dissolving microneedles are typically prepared using water-soluble sugars or polymers to facilitate rapid dissolution in intradermal fluid, compositions that complicate the incorporation of poorly water-soluble vaccine components. Kim et al. (DOI: 10.1021/acsnano.8b04146) overcome this limitation, reporting the development of dissolving microneedles that generate nanomicelles upon dissolution that encapsulate a poorly water-soluble immunomodulator. The researchers based these microneedles on an amphiphilic triblock copolymer (poly(ethylene oxide)-block-poly(propylene oxide)-block-poly(ethylene oxide)) blended with poly(ethylene glycol), which facilitated the formation of micelles. During the fabrication process, the researchers loaded a hydrophobic adjuvant (a ligand for human Toll-like receptor 7 and 8 expressed on a variety of immune cells) and the antigen (OVA) into the microneedle matrix. Their experiments show that the micelles that were formed efficiently migrated to the lymph nodes, where they elicited antitumor immune responses that effectively retarded tumor growth and prophylactically prevented cancers in a mouse model of lymphoma. The authors suggest that these microneedles could become a clinical platform for transdermal vaccination for both therapeutic and prophylactic purposes.
Thus, there is an urgent need for better ways to detect residual cancer during WLC procedures. Toward that end, Davis et al. (DOI: 10.1021/acsnano.8b03217) tested various strategies for using surface-enhanced Raman scattering (SERS) nanoparticles to image bladder cancer tissue. The researchers created three types of gold nanoparticles: two were tagged with human antibodies that actively target bladder cancer-specific proteins CD47 and CA9; the third was tagged with the IgG4 antibody that does not actively target human proteins. Tests showed that the active-targeting SERS nanoparticles readily attached to bladder cancer cells in suspension and could be used for multiplexed imaging. However, on ex vivo bladder tissue, the researchers found that the IgG4-tagged nanoparticle could passively target tumor tissue, a result that the researchers attribute to the enhanced surface permeability and retention effect of the cancer. They conclude that both activeand passive-targeting nanoparticles could accurately classify bladder cancer with different advantages, suggesting that SERS is a promising approach for improving resection of NMIBC.
PAINT-ON TREATMENT FOR MELANOMA Transdermal delivery has been used for a variety of pharmaceuticals, offering convenient self-administration, suitable longterm treatment, avoidance of the first-pass effect, and improved patient compliance. Topical treatments are ideal for skin conditions, delivering high therapeutic concentrations while minimizing systemic toxicity. However, effectively passing through the stratum corneum, the outermost layer of skin, is highly challenging. Nanoparticle-based systems have increasingly been exploited to penetrate this barrier, including transfersomes composed of phospholipids and surfactants. Jiang et al. (DOI: 10.1021/acsnano.8b03800) take advantage of these artificial vesicles by combining transfersomes with a cellpenetrating peptide in an oligopeptide hydrogel that can trap melanoma-fighting chemotherapy directly onto skin. The researchers formulated transfersomes with surfactants including Tween 80 and sodium deoxycholate, which played an important role in altering the arrangement and boosting the fluidity of lipid molecules in the stratum corneum for permeation enhancement. They added the cell-penetrating peptide, R8H3, to improve
TARGETING BLADDER CANCER Worldwide, hundreds of thousands of people are diagnosed each year with bladder cancer. The vast majority of these cases are nonmuscle invasive bladder cancer (NMIBC). The standard of care for this condition is transurethral resection guided by white light cystoscopy (WLC). However, WLC often leads to incomplete resection, with research suggesting that nearly half of patients are left with residual disease. Consequently, bladder cancer has the highest recurrence rate of all cancers at 60−70%. © 2018 American Chemical Society
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Published: October 23, 2018 9639
DOI: 10.1021/acsnano.8b07704 ACS Nano 2018, 12, 9639−9642
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Cite This: ACS Nano 2018, 12, 9639−9642
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effects on cells, suggesting that these dissolved components are biocompatible at their relatively slow dissolution rates. The authors suggest that these results demonstrate the feasibility of using these temporary devices in vivo.
both skin and tumor penetration capabilities further. They then loaded these transfersomes with paclitaxel, a first-line chemotherapy for melanoma, into the highly flexible oligopeptide hydrogel as a reservoir. Fluorescence tests showed that this mixture effectively permeated skin and penetrated tumors in vitro, inducing apoptosis in cultured cancer cells. When the hydrogel was painted onto a mouse model of melanoma that was concurrently treated with Taxol chemotherapy, the anticancer effect was enhanced compared to mice receiving only Taxol. The authors suggest that this formulation could be an effective tool for transdermal delivery of drugs to fight melanoma and other skin diseases.
MAKING THE CUT WITH BIOGRAPHENE KIRIGAMI Most modern electronics are composed of conventional semiconductor components linked by noble metal interconnects through print and lithography processes. However, these devices have several drawbacks, including environmentally harmful life cycles, inability to adapt shape or performance in response to external stimuli, significant bulk, and an inability to accommodate strains without material failure. Some research has sought to address the strain issue through kirigami, the art of papercutting. However, these studies have used a limited selection of materials, including silicon, paper, and elastomers, modified by binary cutting techniques such as laser cutting, masked ion etching, or macroscopic cutting. Switching tracks, Ma et al. (DOI: 10.1021/acsnano.8b04507) applied kirigami to biographene papers made of graphene oxide (GO) multilayers combined with silk fibroin. The researchers used a drag-knife approach for cutting, which enabled not only complete cuts but partial ones that could influence preferential creasing, programmable directionality for out-of-plane buckling, and predefined loci of weakness for controlled material failure. Using this strategy, they successfully implemented a variety of designs, including a one-dimensional stretchable pattern of parallel slits, a two-dimensional stretchable auxetic sheet, a three-dimensional (3D) self-supported pop-up cube and helical spring, a moving 3D pop-up spinner, and a long, flexible conductive wire interconnect. By reducing the GO, the researchers converted these materials into highly conductive substrates, a characteristic that they exploited by developing one structure into a triboelectric energy harvester. The authors suggest that biographene papers hold significant promise for soft electronic components and stretchable energy harvesters capable of complex deformation behavior without losing electromechanical properties.
DELVING INTO CYTOTOXICITY OF DISSOLVING ELECTRONICS Electronics that decompose, degrade, or bioresorb have attracted increasing attention for their potential applications in diagnostics and therapeutics. These systems have been fabricated from a variety of materials. Inorganic semiconductors/dielectrics are particularly intriguing because of their capacity to support device designs aligned with complementary metal−oxide semiconductor (CMOS) technologies. However, the effect of these dissolvable devices, particularly those composed of foundrycompatible materials, on living systems remains unclear. The simple cell viability assays performed thus far do not yield direct insight into cell metabolic activity and other indicators of health. Chang et al. (DOI: 10.1021/acsnano.8b04513) added to the body of knowledge in this field by characterizing the effects of dissolving thin films of Si, SiNx, SiO2, and W on cellular bioactivity and movement. They found that dissolution of each of these materials accelerated over time, yielding Si- or W-based products into the culture media. Mechanical transduction tests with human colon fibroblasts showed no significant effects of the Si-based materials on biological activity related to adhesion and traction, suggesting a lack of toxicity. However, as the concentrations of W-based products in the cell culture environment increased over time, maximum and average tractions tresses declined, and total force magnitudes and strain energies increased, suggesting an adverse effect on cellular health. However, microelectronic devices incorporating these films sourced from a commercial foundry had no significant mechanobiological
SCHWANN CELLS ON THE WING In vivo, most mammalian cells must attach and spread on surfaces in order to survive, to proliferate, and to function. Research has shown that a variety of chemical and physical cues on surfaces help guide cell adhesion, growth, and differentiation. 9640
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In particular, topographic cues can direct cell behavior, such as adhesion, migration, cytoskeletal arrangements, and differentiation. However, the nature of these topographical cues is largely unknown, as are the underlying molecular mechanisms for cell-material interactions. To shed light on this phenomenon, He et al. (DOI: 10.1021/ acsnano.8b00552) took advantage of two different species of butterfly wings: Morpho menelaus, whose wing surface is decorated with parallel ridges spaced about 2 μm apart; and Papilio ulysses telegonus, whose wings have micro- and nanoconcave forms arranged periodically along the ridges. Using these wings as substrates, the researchers grew Schwann cells, specialized glial cells in the peripheral nervous system that play key roles in maintaining neuronal structure and function and repairing damaged nerves. Microscopy showed that cells grown on the Morpho wings formed regular sorting patterns along the grooves. In contrast, the cells seeded on the Papilio wings exhibited random arrangements. Using transcriptome sequencing, bioinformatics analysis, and gene silencing, the researchers found that huntingtin-regulated lysosome activity is a key factor for determining cell growth behavior on Morpho wings. With an eye toward regenerative applications, rat models of sciatic injury showed that silicon tubes fabricated with Morpho wings markedly facilitated nerve regrowth. The authors suggest that these findings could lead to strategies for constructing biomimetic nerve grafts for clinical use.
after 2000 cycles. Microscopy revealed that stretching caused V-shaped cracks to form in the top nanoparticle layer while the nanowire tail end deformed conformably to the substrate without cracking. In contrast, bulk gold films and percolation nanowire films exhibit only U-shaped cracks that do not recover upon strain release. As proof of applicability, the researchers used these enokitake-like films to create stretchable supercapacitors and e-skin nanopatches for monitoring facial expressions. The authors suggest that these films could be used in a myriad of other applications in future elastronics.
OPTIMIZING SUPERCAPACITOR CHARGING SPEED WITH A SLOWER SWEEP For over a century, electric energy storage (EES) has primarily been in the form of batteries; however, electrical double-layer capacitors, also known as supercapacitors or ultracapacitors, have attracted increasing attention due to their ability to charge and to discharge quickly. Despite this advantage, supercapacitors provide only moderate energy densities, which has significantly limited their widespread application. Extensive efforts have been focused on enhancing supercapacitor energy density, including developing room-temperature ionic liquids and optimizing porous electrode materials. Although the highest capacitances and energy densities have been achieved when the average pore size matches the size of a desolvated ion, this design makes charging dynamics sluggish, presumably due to co-ion trapping. Breitsprecher et al. (DOI: 10.1021/acsnano.8b04785) propose a seemingly contradictory solution to speeding up this sluggish charging: applying a slower voltage sweep. The researchers developed molecular dynamics simulations with a model consisting of soft charged spheres and a pair of two slit nanopores. Their experiments showed that when voltage is suddenly applied in a step-like manner, co-ions become trapped in the narrow pores through fast field-driven adsorption of counterions from the bulk electrolyte. Surprisingly, this problem could be avoided by performing slow voltage sweeps with small, incremental changes in voltage over time. They validated their results with simulations of a commonly used room-temperature liquid, BMIM-PF6. Contrary to this finding, discharge was fastest when the voltage is switched off in a step-like fashion. The authors suggest that these results provide a general framework for optimizing supercapacitors that could enable more widespread use.
SURVIVING THE STRETCH WITH ENOKITAKE-LIKE ELASTRONICS For next-generation electronics applications, such as devices that seamlessly integrate with biological components for real-time diagnostics, electronics must shift from current rigid designs to stretchable ones. These elastronic devices will require a combination of stretchability and electrical conductivity that has been challenging to accomplish to date. One strategy that has found success thus far is depositing active nanomaterials onto or into elastomers to create percolation networks. However, large or repeated strains compromise durability, leading to delamination and/or cracks at the interface between the soft and rigid materials. Seeking more robust elastronics, Wang et al. (DOI: 10.1021/ acsnano.8b05019) report a design in which gold nanowires topped with nanoparticles, resembling the straw mushrooms known as enokitake, grow on elastomeric substrates to form percolation networks that maintain conductivity even after repeated high levels of strain. The researchers created these nanowire films using a method similar to that of seed-mediated electroless plating on rigid surfaces. When grown on Ecoflex substrates, tests showed that these films exhibited high stretchability of up to 800% without losing conductivity, even 9641
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MONOLAYER PATTERNING WITH ELECTRON BEAM LITHOGRAPHY Electron beam lithography has long been used as a tool to pattern diverse materials at the nanoscale. This technique typically relies on the use of a resist coating that acts as a sacrificial pattern transfer medium as it is modified under exposure to an electron beam, enabling its subsequent removal from either exposed or unexposed areas of the substrate. To improve resolution of this technique, recent research has focused on the use of organic monolayers as resists. However, exposure to the e-beam often damages the monolayer structure, leading to unwanted topographic, structural, and chemical transformations. Seeking a different approach to monolayer patterning, Maoz et al. (DOI: 10.1021/acsnano.8b03416) describe a technique called interfacial electron beam lithography (IEBL). This method combines elements of constructive lithography, in which the outer surface of an initially homogeneous monolayer is locally modified while preserving the monolayer structural integrity and overall molecular organization, with the recent discovery of a class of radiation-induced interfacial chemical transformations confined to the contact surface between two solids. The researchers use this technique to modify surface −CH 3 groups on n-octadecyltrichlorosilane (OTS) to −COOH. The authors demonstrate the versatility of this technique in two setups: OTS sandwiched between poly(vinyl alcohol) and Si or between Ag(O) and Si. The researchers verified these structural and chemical transformations using a semiquantitative surface characterization that combined multimode atomic force microscopy imaging with postpatterning surface chemical modifications and quantitative micro-Fourier transform infrared spectroscopy. The authors suggest that this technique offers attractive opportunities for chemical nanopatterning using the simplest, commonly used organosilane monolayers.
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