Auranofin-Loaded Chitosan Nanoparticles Demonstrate Potency against Triple-Negative Breast Cancer.

Triple-negative breast cancer (TNBC) remains a clinical challenge due to molecular, metabolic, and genetic heterogeneity as well as the lack of validated drug targets. Thus, therapies or delivery paradigms are needed. Gold-derived compounds including the FDA-approved drug, auranofin have shown promise as effective anticancer agents against several tumors. To improve the solubility and bioavailability of auranofin, we hypothesized that the nanodelivery of auranofin using biodegradable chitosan modified polyethylene glycol (PEG) nanoparticles (NPs) will enhance anticancer activity against TNBC by comparing the best nanoformulation with the free drug. The selection of the nanoformulation was based on synthesis of various chitosan PEG copolymers via formaldehyde-mediated engraftment of PEG onto chitosan to form [chitosan-g-PEG] copolymer. Furthermore, altered physiochemical properties of the copolymer was based on the formaldehyde ratio towards nanoparticles (CP 1-4 NPs). Following the recruitment of PEG onto the chitosan polymer surface, we explored how this process influenced the stiffness of the nanoparticle using atomic force microscopy (AFM), a factor crucial for in vitro and in vivo studies. Our objective was to ensure the full functionality and inherent properties of chitosan as the parent polymer was maintained without allowing PEG to overshadow chitosan's unique cationic properties while improving solubility in neutral pH. Hence, CP 2 NP was chosen. To demonstrate the efficacy of CP 2 NP as a good delivery carrier for auranofin, we administered a dose of 3 mg/kg of auranofin, in contrast to free auranofin, which was given at 5 mg/kg. In vivo studies revealed the potency of encapsulated auranofin against TNBC cells with a severe necrotic effect following treatment superior to that of free auranofin. In conclusion, chitosan-g-PEG nanoparticles have the potential to be an excellent delivery system for auranofin, increasing its effectiveness and potentially reducing its clinical limitations.

Ultra-Narrow Phosphorene Nanoribbons Produced by Facile Electrochemical Process.

Phosphorene nanoribbons (PNRs) have inspired strong research interests to explore their exciting properties that are associated with the unique two-dimensional (2D) structure of phosphorene as well as the additional quantum confinement of the nanoribbon morphology, providing new materials strategy for electronic and optoelectronic applications. Despite several important properties of PNRs, the production of these structures with narrow widths is still a great challenge. Here, a facile and straightforward approach to synthesize PNRs via an electrochemical process that utilize the anisotropic Na+ diffusion barrier in black phosphorus (BP) along the [001] zigzag direction against the [100] armchair direction, is reported. The produced PNRs display widths of good uniformity (10.3 ± 3.8 nm) observed by high-resolution transmission electron microscopy, and the suppressed B2g vibrational mode from Raman spectroscopy results. More interestingly, when used in field-effect transistors, synthesized bundles exhibit the n-type behavior, which is dramatically different from bulk BP flakes which are p-type. This work provides insights into a new synthesis approach of PNRs with confined widths, paving the way toward the development of phosphorene and other highly anisotropic nanoribbon materials for high-quality electronic applications.

n-type charge transport in heavily p-doped polymers.

It is commonly assumed that charge-carrier transport in doped π-conjugated polymers is dominated by one type of charge carrier, either holes or electrons, as determined by the chemistry of the dopant. Here, through Seebeck coefficient and Hall effect measurements, we show that mobile electrons contribute substantially to charge-carrier transport in π-conjugated polymers that are heavily p-doped with strong electron acceptors. Specifically, the Seebeck coefficient of several p-doped polymers changes sign from positive to negative as the concentration of the oxidizing agents FeCl3 or NOBF4 increase, and Hall effect measurements for the same p-doped polymers reveal that electrons become the dominant delocalized charge carriers. Ultraviolet and inverse photoelectron spectroscopy measurements show that doping with oxidizing agents results in elimination of the transport gap at high doping concentrations. This approach of heavy p-type doping is demonstrated to provide a promising route to high-performance n-type organic thermoelectric materials.

Altering the radiation chemistry of electron-beam lithography with a reactive gas: a study of Teflon AF patterning under water vapor.

Variable-pressure electron-beam lithography (VP-EBL) employs an ambient gas at subatmospheric pressure to reduce charging of insulating films and substrates during electron exposure. In this work, VP-EBL proves to be an efficient method for patterning a widely used, but challenging to process, fluoropolymer, Teflon AF. However, rather than solely mitigating charging, the ambient gas is found to alter the radiation chemistry of the exposure process. Specifically, irradiating Teflon AF under water vapor increases the dissolution rate of the exposed regions in non-fluorinated solvents and enables complete patterning in a positive tone process. When compared to conventional e-beam resists, the contrast (≈4), clearing dose (<700 µC cm-2), and resolution (≈40 nm half-pitch) of Teflon AF are adequate. However, these figures of merit are quite remarkable when the process is considered as a means for directly patterning a functional material with extremely low surface energy, dielectric constant, and refractive index. Intriguingly, VP-EBL of Teflon AF under water vapor also exhibits non-reciprocity, through dose-rate dependence, and exhibits anomalous proximity effects. Thus, the influence of the ambient gas on radiation chemistry must be considered for VP-EBL, and some of the resulting effects may offer significant benefits for patterning both functional and lithographic materials.

Graphene used as a lateral force microscopy calibration material in the low-load non-linear regime.

A lateral force microscopy (LFM) calibration technique utilizing a random low-profile surface is proposed that is successfully employed in the low-load non-linear frictional regime using a single layer of graphene on a supporting oxide substrate. This calibration at low loads and on low friction surfaces like graphene has the benefit of helping to limit the wear of the LFM tip during the calibration procedure. Moreover, the low-profiles of the calibration surface characteristic of these layered 2D materials, on standard polished oxide substrates, result in a nearly constant frictional, adhesive, and elastic response as the tip slides over the surface, making the determination of the calibration coefficient robust. Through a detailed calibration analysis that takes into account non-linear frictional response, it is found that the adhesion is best described by a nearly constant vertical orientation, rather than the more commonly encountered normally directed adhesion, as the single asperity passes over the low-profile graphene-coated oxide surface.

Nonlinear Ballistic Transport in an Atomically Thin Material.

Ultrashort devices that incorporate atomically thin components have the potential to be the smallest electronics. Such extremely scaled atomically thin devices are expected to show ballistic nonlinear behavior that could make them tremendously useful for ultrafast applications. While nonlinear diffusive electron transport has been widely reported, clear evidence for intrinsic nonlinear ballistic transport in the growing array of atomically thin conductors has so far been elusive. Here we report nonlinear electron transport of an ultrashort single-layer graphene channel that shows quantitative agreement with intrinsic ballistic transport. This behavior is shown to be distinctly different than that observed in similarly prepared ultrashort devices consisting, instead, of bilayer graphene channels. These results suggest that the addition of only one extra layer of an atomically thin material can make a significant impact on the nonlinear ballistic behavior of ultrashort devices, which is possibly due to the very different chiral tunneling of their charge carriers. The fact that we observe the nonlinear ballistic response at room temperature, with zero applied magnetic field, in non-ultrahigh vacuum conditions and directly on a readily accessible oxide substrate makes the nanogap technology we utilize of great potential for achieving extremely scaled high-speed atomically thin devices.

Integrated nanotubes, etch tracks, and nanoribbons in crystallographic alignment to a graphene lattice.

Carbon nanotubes, few-layer graphene, and etch tracks exposing insulating SiO2 regions are integrated into nanoscale systems with precise crystallographic orientations. These integrated systems consist of nanotubes grown across nanogap etch tracks and nanoribbons formed within the few-layer graphene films. This work is relevant to the integration of semiconducting, conducting, and insulating nanomaterials together into precise intricate systems.

Synthesis and characterization of p-n homojunction-containing zinc oxide nanowires.

We illustrate a simple method to synthesize highly ordered ZnO axial p-n homojunction-containing nanowires using a low temperature method, and on a variety of substrates. X-ray diffraction, scanning transmission electron microscopy, scanning electron microscopy, and Raman spectroscopy are used to reveal high quality single-crystalline wires with a [001] growth direction. The study of electrical transport through a single nanowire based device and cathodoluminescence via scanning transmission electron microscopy demonstrates that an axial p-n junction exists within each ZnO nanowire. This represents the first low temperature synthesis of axial p-n homojunction-containing ZnO nanowires with uniform and controllable diameters.

Crystallographically aligned carbon nanotubes grown on few-layer graphene films.

Carbon nanotubes are grown on few-layer graphene films using chemical vapor deposition without a carbon feedstock gas. We find that the nanotubes show a striking alignment to specific crystal orientations of the few-layer graphene films. The nanotubes are oriented predominantly at 60 degree intervals and are offset 30 degrees from crystallographically oriented etch tracks, indicating alignment to the armchair axes of the few-layer graphene films. Nanotubes grown on various thicknesses of few-layer graphene under identical process conditions show that the thinnest films, in the sub-6 atomic layer regime, demonstrate significantly improved crystallographic alignment. Intricate crystallographic patterns are also observed having sharp kinks with bending radii less than the ∼10 nm lateral resolution of the electron and atomic force microscopy used to image them. Some of these kinks occur independently without interactions between nanotubes while others result when two nanotubes intersect. These intersections can trap nanotubes between two parallel nanotubes resulting in crystallographic back and forth zigzag geometries. These interactions suggest a tip-growth mechanism such that the catalyst particles remain within several nanometers of the few-layer graphene surface as they move leaving a nanotube in their wake.

High-on/off-ratio graphene nanoconstriction field-effect transistor.

A method is reported to pattern monolayer graphene nanoconstriction field-effect transistors (NCFETs) with critical dimensions below 10 nm. NCFET fabrication is enabled by the use of feedback-controlled electromigration (FCE) to form a constriction in a gold etch mask that is first patterned using conventional lithographic techniques. The use of FCE allows the etch mask to be patterned on size scales below the limit of conventional nanolithography. The opening of a confinement-induced energy gap is observed as the NCFET width is reduced, as evidenced by a sharp increase in the NCFET on/off ratio. The on/off ratios obtained with this procedure can be larger than 1000 at room temperature for the narrowest devices; this is the first report of such large room-temperature on/off ratios for patterned graphene FETs.

Surface potentials and layer charge distributions in few-layer graphene films.

Graphene-derived nanomaterials are emerging as ideal candidates for postsilicon electronics. Elucidating the electronic interaction between an insulating substrate and few-layer graphene (FLG) films is crucial for device applications. Here, we report electrostatic force microscopy (EFM) measurements revealing that the FLG surface potential increases with film thickness, approaching a "bulk" value for samples with five or more graphene layers. This behavior is in sharp contrast with that expected for conventional conducting or semiconducting films, and derives from unique aspects of charge screening by graphene's relativistic low energy carriers. EFM measurements resolve previously unseen electronic perturbations extended along crystallographic directions of structurally disordered FLGs, likely resulting from long-range atomic defects. These results have important implications for graphene nanoelectronics and provide a powerful framework by which key properties can be further investigated.

Crystallographic etching of few-layer graphene.

We demonstrate a method by which few-layer graphene samples can be etched along crystallographic axes by thermally activated metallic nanoparticles. The technique results in long (>1 microm) crystallographic edges etched through to the insulating substrate, making the process potentially useful for atomically precise graphene device fabrication. This advance could enable atomically precise construction of integrated circuits from single graphene sheets with a wide range of technological applications.

Real-time TEM imaging of the formation of crystalline nanoscale gaps.

We present real-time transmission electron microscopy of nanogap formation by feedback controlled electromigration that reveals a remarkable degree of crystalline order. Crystal facets appear during feedback controlled electromigration indicating a layer-by-layer, highly reproducible electromigration process avoiding thermal runaway and melting. These measurements provide insight into the electromigration induced failure mechanism in sub-20 nm size interconnects, indicating that the current density at failure increases as the width decreases to approximately 1 nm.

Parallel fabrication of nanogap electrodes.

We have developed a technique for simultaneously fabricating large numbers of nanogaps in a single processing step using feedback-controlled electromigration. Parallel nanogap formation is achieved by a balanced simultaneous process that uses a novel arrangement of nanoscale shorts between narrow constrictions where the nanogaps form. Because of this balancing, the fabrication of multiple nanoelectrodes is similar to that of a single nanogap junction. The technique should be useful for constructing complex circuits of molecular-scale electronic devices.

Clean electromigrated nanogaps imaged by transmission electron microscopy.

Electromigrated nanogaps have shown great promise for use in molecular scale electronics. We have fabricated nanogaps on free-standing transparent SiN(x) membranes which permit the use of transmission electron microscopy (TEM) to image the gaps. The electrodes are formed by extending a recently developed controlled electromigration procedure and yield a nanogap with approximately 5 nm separation clear of any apparent debris. The gaps are stable, on the order of hours as measured by TEM, but over time (months) relax to about 20 nm separation determined by the surface energy of the Au electrodes. A major benefit of electromigrated nanogaps on SiN(x) membranes is that the junction pinches in away from residual metal left from the Au deposition which could act as a parasitic conductance path. This work has implications to the design of clean metallic electrodes for use in nanoscale devices where the precise geometry of the electrode is important.