Evidence of thickness-dependent surface-induced ferroelectricity in few-layer germanium sulfide obtained via scanning tunneling spectroscopy.

The discovery of ferroelectricity in two-dimensional van der Waals materials has sparked enormous interest from the scientific community, due to its possible applications in next-generation nanoelectronic devices, such as random-access memory devices, digital signal processors, and solar cells, among others. In the present study, we used vapor phase deposition to synthesize ultrathin germanium sulfide nano-flakes on a highly oriented pyrolytic graphite substrate. Nanostructures of variable thicknesses were characterized using scanning tunneling microscopy and spectroscopy. Tunneling currents under forward and backward biases were measured as a function of nano-flake thickness. Remarkably, we clearly observed a hysteresis pattern, which we attributed to surface ferroelectric behavior, consistent with the screening conditions of polarization charges. The effect increases as the number of layers is reduced. This experimental result may be directly applicable to miniaturized memory devices, given the two-dimensional nature of this effect.

Scanning Tunneling Spectroscopy Method for the Prediction of Semiconductor Heterojunction Performance as a Prequel for Device Development.

The prediction of semiconductor device performance is a persistent challenge in materials science, and the ability to anticipate useful specifications prior to construction is crucial for enhancing the overall efficiency. In this study, we investigate the constituents of a solar cell by employing scanning tunneling microscopy (STM) and spectroscopy (STS). Through our observations, we identify a spatial distribution of the dopant type in thin films of materials that were designed to present major p-doping for germanium sulfide (GeS) and dominant n-doping for tin disulfide (SnS2). By generating separate STS maps for each semiconductor film and conducting a statistical analysis of the gap and doping distribution, we determine intrinsic limitations for the solar cell efficiency that must be understood prior to processing. Subsequently, we fabricate a solar cell utilizing these materials (GeS and SnS2) via vapor phase deposition and carry out a characterization using standard J-V curves under both dark/illuminated irradiance conditions. Our devices corroborate the expected reduced efficiency due to doping fluctuation but exhibit stable photocurrent responses. As originally planned, quantum efficiency measurements reveal that the peak efficiency of our solar cell coincides with the range where the standard silicon solar cells sharply decline. Our STS method is suggested as a prequel to device development in novel material junctions or deposition processes where fluctuations of doping levels are retrieved due to intrinsic material characteristics such as the occurrence of defects, roughness, local chemical segregation, and faceting or step bunching.

Review: using rolled-up tubes for strain-tuning the optical properties of quantum emitters.

Rolled-up tubes based on released III-V heterostructures have been extensively studied and established as optical resonators in the last two decades. In this review, we discuss how light emitters (quantum wells and quantum dots) are influenced by the inherently asymmetric strain state of these tubes. Therefore, we briefly review whispering gallery mode resonators built from rolled-up III-V heterostructures. The curvature and its influence over the diameter of the rolled-up micro- and nanotubes are discussed, with emphasis on the different possible strain states that can be produced. Experimental techniques that access structural parameters are essential to obtain a complete and correct image of the strain state for the emitters inside the tube wall. In order to unambiguously extract such strain state, we discuss x-ray diffraction results in these systems, providing a much clearer scenario compared to a sole tube diameter analysis, which provides only a first indication of the lattice relaxation in a given tube. Further, the influence of the overall strain lattice state on the band structure is examined via numerical calculations. Finally, experimental results for the wavelength shift of emissions due to the tube strain state are presented and compared with theoretical calculations available in literature, showing that the possibility to use rolled-up tubes to permanently strain engineer the optical properties of build-in emitters is a consistent method to induce the appearance of electronic states unachievable by direct growth methods.

Alpha-tocopheryl succinate and doxorubicin-loaded liposomes improve drug uptake and tumor accumulation in a murine breast tumor model.

Liposomes composed of a rigid bilayer have high plasma stability; however, they can be challenged in efficacy due to complications in releasing the encapsulated drug as well as being internalized by the tumor cell. On the other hand, fusogenic liposomes may fuse with the plasmatic membrane and release encapsulated material directly into the cytoplasm. In a previous study, fusogenic liposomes composed of alpha-tocopheryl succinate (TS) and doxorubicin (DOX) were developed (pHSL-TS-DOX). These stabilized tumor growth and reduced toxicity compared to a commercial formulation. In the present study, we investigated whether cellular uptake or DOX accumulation in the tumor could justify the better performance of the pHSL-TS-DOX formulation. Release, deformability, and DOX plasmatic concentration studies were also carried out. pHSL-TS-DOX showed an adequate release profile and demonstrated characteristics of a deformable formulation. Data from apoptosis, cell cycle, and nuclear morphology studies have shown that the induction of cell death caused by pHSL-TS-DOX occurred more quickly. Higher DOX cellular uptake and tumor accumulation were observed when pHSL-TS-DOX was administered, demonstrating better drug delivery capacity. Therefore, better DOX uptake as well as tumor accumulation explain the great antitumor activity previously demonstrated for this formulation.

Aggregation-Induced Emission and Temperature-Dependent Luminescence of Potassium Perylenetetracarboxylate.

Investigation of temperature-dependent photoluminescent properties of potassium perylene-3,4,9,10-tetracarboxylate (K4PTC), a molecule with no internal rotational degrees of freedom, shows aggregation-induced enhanced emission at room temperature. The different excitonic emission processes are dependent of temperature, some of which quenches in an intermediate temperature range (from 50 to 150 K). The exciton excited states switching phenomenon from "dark" to "bright" states is observed and its explained using Herzberg-Teller selection rule. K4PTC is a molecule comparable to the size of its precursor, perylene-3,4,9,10-tetracarboxylic anhydride (PTCDA) and is highly soluble in water, contrary to PTCDA, which is poorly soluble in most solvents. Powder x-ray diffraction measurements corroborate a lesser degree of ordering of bulk K4PTC compared to bulk PTCDA. The green luminescent molecule could, in principle, be used as a biomarker, or in photodynamic therapy, if further studies show relatively low toxicity.

Sub-diffractional cavity modes of terahertz hyperbolic phonon polaritons in tin oxide.

Hyperbolic phonon polaritons have recently attracted considerable attention in nanophotonics mostly due to their intrinsic strong electromagnetic field confinement, ultraslow polariton group velocities, and long lifetimes. Here we introduce tin oxide (SnO2) nanobelts as a photonic platform for the transport of surface and volume phonon polaritons in the mid- to far-infrared frequency range. This report brings a comprehensive description of the polaritonic properties of SnO2 as a nanometer-sized dielectric and also as an engineered material in the form of a waveguide. By combining accelerator-based IR-THz sources (synchrotron and free-electron laser) with s-SNOM, we employed nanoscale far-infrared hyper-spectral-imaging to uncover a Fabry-Perot cavity mechanism in SnO2 nanobelts via direct detection of phonon-polariton standing waves. Our experimental findings are accurately supported by notable convergence between theory and numerical simulations. Thus, the SnO2 is confirmed as a natural hyperbolic material with unique photonic properties essential for future applications involving subdiffractional light traffic and detection in the far-infrared range.

Emergence of Supramolecular Order from Combined Linear Amphiphilic and Diphosphonate Molecules.

Self-assembled molecules exhibit key functionalities for the development of novel technologies and applications. Usually, molecular systems that exhibit long-range positional order are employed in their pure form. In this work, we observe that a combination of an amphiphilic molecule, tetradecyl-phosphonic acid (TPA), and a diphosphonate molecule with a similar length, 1,10-decyldiphosphonic acid (DdPA), induces distinct long-range ordered structures depending on the relative volume of dilutions used for drop coating. Starting from 0.2 mM diluted ethanol solutions of each molecule and combining both in distinct proportions that range from 1:20 to 20:1, we were able to identify periodic molecular structures that consist of three and five molecules of TPA and DdPA arranged in symmetries and were retrieved by synchrotron X-ray diffraction. The possibility of deterministically building up such structures can be further developed to induce surface and bulk behaviors that better suit applications such as coatings for chemical and biological studies, as well as to engineer layers used in organic electronic applications.

Mapping the local dielectric constant of a biological nanostructured system.

The aim of this work is to determine the varying dielectric constant of a biological nanostructured system via electrostatic force microscopy (EFM) and to show how this method is useful to study natural photonic crystals. We mapped the dielectric constant of the cross section of the posterior wing of the damselfly Chalcopteryx rutilans with nanometric resolution. We obtained structural information on its constitutive nanolayers and the absolute values of their dielectric constant. By relating the measured profile of the static dielectric constant to the profile of the refractive index in the visible range, combined with optical reflectance measurements and simulation, we were able to describe the origin of the strongly iridescent wing colors of this Amazonian rainforest damselfly. The method we demonstrate here should be useful for the study of other biological nanostructured systems.

Mechanistic insights into the intracellular release of doxorubicin from pH-sensitive liposomes.

pH-sensitive liposomes are interesting carriers for drug-delivery, undertaking rapid bilayer destabilization in response to pH changes, allied to tumor accumulation, a desirable behavior in the treatment of cancer cells. Previously, we have shown that pH-sensitive liposomes accumulate in tumor tissues of mice, in which an acidic environment accelerates drug delivery. Ultimately, these formulations can be internalized by tumor cells and take the endosome-lysosomal route. However, the mechanism of doxorubicin release and intracellular traffic of pH-sensitive liposomes remains unclear. To investigate the molecular mechanisms underlying the intracellular release of doxorubicin from pH-sensitive liposomes, we followed HeLa cells viability, internalization, intracellular trafficking, and doxorubicin's intracellular delivery mechanisms from pH-sensitive (SpHL-DOX) and non-pH-sensitive (nSpHL-DOX) formulations. We found that SpHL-DOX has faster internalization kinetics and intracellular release of doxorubicin, followed by strong nuclear accumulation compared to nSpHL-DOX. The increased nuclear accumulation led to the activation of cleaved caspase-3, which efficiently induced apoptosis. Remarkably, we found that chloroquine and E64d enhanced the cytotoxicity of SpHL-DOX. This knowledge is paramount to improve the efficiency of pH-sensitive liposomes or to be used as a rational strategy for developing new formulations to be applied in vivo.

Novel self-nanoemulsifying drug-delivery system enhances antileukemic properties of all-trans retinoic acid.

Aim: All-trans retinoic acid (ATRA) shows erratic oral bioavailability when administered orally against leukemia, which can be solved through its incorporation in self-nanoemulsifying drug-delivery systems (SEDDS). The SEDDS developed contained a hydrophobic ion pair between benzathine (BZT) and ATRA and was enriched with tocotrienols by the input of a palm oil tocotrienol rich fraction (TRF) in its composition. Results: SEDDS-TRF-ATRA-BZT allowed the formation of emulsions with nanometric size that retained ATRA within their core after dispersion. Pharmacokinetic parameters after oral administration of SEDDS-TRF-ATRA-BZT in mice were improved compared with what was seen for an ATRA solution. Moreover, SEDDS-TRF-ATRA-BZT had improved activity against HL-60 cells compared with SEDDS without TRF. Conclusion: SEDDS-TRF-ATRA-BZT is a promising therapeutic choice over ATRA conventional medicine.

Physical and biological effects of paclitaxel encapsulation on disteraroylphosphatidylethanolamine-polyethyleneglycol polymeric micelles.

Simple size observations of 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethyleneglycol)-2000] (DSPE-mPEG2000) polymeric micelles (PM) with different compositions including or not paclitaxel (PTX) are unable to evidence changes on the nanocarrier structure. In such system a detailed characterization using highly sensitive techniques such as X-ray scattering and asymmetric flow field flow fractionation coupled to multi-angle laser light scattering and dynamic light scattering (AF4-MALS-DLS) is mandatory to observe effects that take place by the addition of PTX and/or more lipid-polymer at PM, leading to complex changes on the structure of micelles, as well as in their supramolecular organization. SAXS and AF4-MALS-DLS suggested that PM can be found in the medium separately and highly organized, forming clusters of PM in the latter case. SAXS fitted parameters showed that adding the drug does not change the average PM size since the increase in core radius is compensated by the decrease in shell radius. SAXS observations indicate that PEG conformation takes place, changing from brush to mushroom depending on the PM composition. These findings directly reflect in in vivo studies of blood clearance that showed a longer circulation time of blank PM when compared to PM containing PTX.

Treatment for chemical burning using liquid crystalline nanoparticles as an ophthalmic delivery system for pirfenidone.

Some recent studies have shown that pirfenidone (PFD) has favorable results in the healing process of the cornea. However, PFD in solution exhibits short half-life after topical application, and in this context, a liquid crystal nanoparticle system containing PFD (PFD-LCNPs) was developed. The nanoparticles were characterized by transmission electron microscopy, atomic force microscopy, small angle X-ray diffraction and polarized light microscopy. The PFD-LCNPs had particle size and zeta potential of 247.3 nm and -33.60 mV (stores at 4 °C), respectively, and 257.5 nm and -46.00 mV (stored at 25 °C), respectively. The pH of the formulation was 6.9 and the encapsulation efficiency was 35.9%. The in vitro release profiles indicated that PFD sustained release from PFD-LCNPs for up to 12 h. In vitro study of ocular irritation (HET-CAM test) concluded that components of the formulation are well tolerated for ocular administration. Corneal re-epithelialization time after chemical burning was significantly reduced in rabbits treated with PFD-loaded LCNPs when compared to the group treated with a vehicle. In addition, the anti-inflammatory action of pirfenidone was observed by reducing myeloperoxidase activity (MPO) and inflammatory cells in the histology of the tissues of animals treated with PFD-LCNPs. These findings indicated that the PFD-LCNPs might have the potential for effective ocular drug delivery.

Formation of BixSey Phases Upon Annealing of the Topological Insulator Bi2Se3: Stabilization of In-Depth Bismuth Bilayers.

The goal of this work is to study transformations that occur upon heating Bi2Se3 to temperatures up to 623 K. X-ray diffraction (XRD) and scanning tunneling microscopy (STM) and spectroscopy (STS) techniques were used in our investigation. XRD was measured following the 00L and 01L truncation rods. These measurements revealed that upon heating there is a coexistence of a major Bi2Se3 phase and other ones that present structures of quintuple-layers intercalated with Bismuth bilayers. STM measurements of the surface of this material showed the presence of large hexagonal BixSey domains embedded in a Bi2Se3 matrix. STS experiments were employed to map the local electronic density of states and characterize the modifications imposed by the presence of the additional phases. Finally, density functional theory (DFT) calculations were performed to support these findings.

Observation of partial relaxation mechanisms via anisotropic strain relief on epitaxial islands using semiconductor nanomembranes.

In this work we attempt to directly observe anisotropic partial relaxation of epitaxial InAs islands using transmission electron microscopy (TEM) and synchrotron x-ray diffraction on a 15 nm thick InAs:GaAs nanomembrane. We show that under such conditions TEM provides improved real-space statistics, allowing the observation of partial relaxation processes that were not previously detected by other techniques or by usual TEM cross section images. Besides the fully coherent and fully relaxed islands that are known to exist above previously established critical thickness, we prove the existence of partially relaxed islands, where incomplete 60° half-loop misfit dislocations lead to a lattice relaxation along one of the 〈110〉 directions, keeping a strained lattice in the perpendicular direction. Although individual defects cannot be directly observed, their implications to the resulting island registry are identified and discussed within the frame of half-loops propagations.

Synthesis, characterization and radiolabeling of polymeric nano-micelles as a platform for tumor delivering.

The use of nanoparticles for diagnostic approaches leads to higher accumulation in the targeting tissue promoting a better signal-to-noise ratio and consequently, early tumor detection through scintigraphic techniques. Such approaches have inherent advantages, including the possibility of association with a variety of gamma-emitting radionuclides available, among them, Tecnethium-99m (99mTc). 99mTc is readily conjugated with nanoparticles using chelating agents, such as diethylenetriaminepentaacetic acid (DTPA). Leveraging this approach, we synthesized polymeric micelles (PM) consisting of 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethyleneglycol)-2000] (DSPE-mPEG2000) functionalized with DTPA for radiolabeling with 99mTc. Micelles made up of DSPE-mPEG2000 and DSPE-PEG2000-DTPA had a mean diameter of ∼10nm, as measured by DLS and SAXS techniques, and a zeta potential of -2.7±1.1mV. Radiolabeled micelles exhibited high radiochemical yields and stability. In vivo assays indicated long blood circulation time (456.3min). High uptake in liver, spleen and kidneys was observed in the biodistribution and imaging studies on healthy and tumor-bearing mice. In addition, a high tumor-to-muscle ratio was detected, which increased over time, showing accumulation of the PM in the tumor region. These findings indicate that this system is a promising platform for simultaneous delivery of therapeutic agents and diagnostic probes.

Phase behavior of dioleyphosphatidylethanolamine molecules in the presence of components of pH-sensitive liposomes and paclitaxel.

Paclitaxel is a potent antimicrotubule chemotherapeutic agent widely used for clinical treatment of a variety of solid tumors. However, the low solubility of the drug in aqueous medium and the toxic effects of the commercially available formulation, Taxol(®), has hindered its clinical application. To overcome these paclitaxel-related disadvantages, several drug delivery approaches have been thoroughly investigated. In this context, our research group has developed long-circulating and pHsensitive liposomes containing paclitaxel composed of dioleylphosphatidylethanolamine, cholesterylhemisuccinate and distearoylphosphatidylethanolamine-polyethylene glycol2000, which have shown to be very promising carriers for this taxane. For the destabilization of pH-sensitive liposomal systems and the release of the encapsulated drug in the cytoplasm of tumor cells, the occurrence of a phase transition from a lamellar to a non-lamellar phase of dioleylphosphatidylethanolamine molecules is essential. Two techniques, differential scanning calorimetry and small angle X-ray scattering, were used to investigate the influence of the liposomal components and paclitaxel in the phase transition process of dioleylphosphatidylethanolamine molecules and to evaluate the pH-sensitivity of the formulation under low hydration conditions. The findings clearly evidence the phase transition of dioleylphosphatidylethanolamine molecules in the presence and absence of PTX indicating that the introduction of the drug in the system does not bring damage to the pH-sensitivity of the system, which resulting in liposome destabilization at low pH regions and encapsulated paclitaxel release preferentially in a desired target tissue.

Graphene/h-BN plasmon-phonon coupling and plasmon delocalization observed by infrared nano-spectroscopy.

We observed the coupling of graphene Dirac plasmons with different surfaces using scattering-type scanning near-field optical microscopy integrated into a mid-infrared synchrotron-based beamline. A systematic investigation of a graphene/hexagonal boron nitride (h-BN) heterostructure is carried out and compared with the well-known graphene/SiO2 heterostructure. Broadband infrared scanning near-field optical microscopy imaging is able to distinguish between the graphene/h-BN and the graphene/SiO2 heterostructure as well as differentiate between graphene stacks with different numbers of layers. Based on synchrotron infrared nanospectroscopy experiments, we observe a coupling of surface plasmons of graphene and phonon polaritons of h-BN (SPPP). An enhancement of the optical band at 817 cm(-1) is observed at graphene/h-BN heterostructures as a result of hybridization between graphene plasmons and longitudinal optical phonons of h-BN. Furthermore, longitudinal optical h-BN modes are preserved on suspended graphene regions (bubbles) where the graphene sheet is tens of nanometers away from the surface while the amplitude of transverse optical h-BN modes decrease.

PEGylated cationic nanoemulsions can efficiently bind and transfect pIDUA in a mucopolysaccharidosis type I murine model.

Mucopolysaccharidosis type I (MPS I) is an autosomal disease caused by alpha-L-iduronidase deficiency. This study proposed the use of cationic nanoemulsions as non-viral vectors for a plasmid (pIDUA) containing the gene that codes for alpha-L-iduronidase. Nanoemulsions composed of medium chain triglycerides (MCT)/1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE)/1,2-dioleoyl-sn-glycero-3-trimethylammonium propane (DOTAP)/1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[amino(polyethylene glycol)-2000] (DSPE-PEG) were prepared by high pressure homogenization. Formulations were prepared by the adsorption or encapsulation of preformed pIDUA-DOTAP complexes into the oil core of nanoemulsions at different charge ratios. pIDUA complexed was protected from enzymatic degradation by DNase I. The physicochemical characteristics of complexes in protein-containing medium were mainly influenced by the presence of DSPE-PEG. Bragg reflections corresponding to a lamellar organization were identified for blank formulations by energy dispersive X-ray diffraction, which could not be detected after pIDUA complexation. The intravenous injection of these formulations in MPS I knockout mice led to a significant increase in IDUA activity (fluorescence assay) and expression (RT-qPCR) in different organs, especially the lungs and liver. These findings were more significant for formulations prepared at higher charge ratios (+4/-), suggesting a correlation between charge ratio and transfection efficiency. The present preclinical results demonstrated that these nanocomplexes represent a potential therapeutic option for the treatment of MPS I.

Ursolic acid incorporation does not prevent the formation of a non-lamellar phase in pH-sensitive and long-circulating liposomes.

Ursolic acid (UA) is a triterpene found in different plant species that has been shown to possess significant antitumor activity. However, UA presents a low water solubility, which limits its biological applications. In this context, our research group has proposed the incorporation of UA in long-circulating and pH-sensitive liposomes (SpHL-UA).These liposomes, composed of dioleylphosphatidylethanolamine (DOPE), cholesteryl hemisuccinate (CHEMS), and distearoylphosphatidylethanolamine-polyethylene glycol2000 (DSPE-PEG2000), were shown to be very promising carriers for UA. Considering that the release of UA from SpHL-UA and its antitumor activity depend upon the occurrence of the lamellar to non-lamellar phase transition of DOPE, in the present work, the interactions of UA with the components of the liposomes were evaluated, aiming to clarify their role in the structural organization of DOPE. The study was carried out by differential scanning calorimetry (DSC) and small-angle X-ray scattering (SAXS) under low hydration conditions. DSC studies revealed that DOPE phase transition temperatures did not shift significantly upon UA addition. On the other hand, in SAXS studies, a different pattern of DOPE phase organization was observed in the presence of UA, with the occurrence of the cubic phase Im3m at 20 °C and the cubic phase Pn3m at 60 °C. These findings suggest that UA interacts with the lipids and changes their self-assembly. However, these interactions between the lipids and UA were unable to eliminate the lamellar to non-lamellar phase transition, which is essential for the cytoplasmic delivery of UA molecules from SpHL-UA.

Chemical stabilization and improved thermal resilience of molecular arrangements: possible formation of a surface network of bonds by multiple pulse atomic layer deposition.

In this work, we make use of an atomic layer deposition (ALD) surface reaction based on trimethyl-aluminum (TMA) and water to modify O-H terminated self-assembled layers of octadecylphosphonic acid (OPA). The structural modifications were investigated by X-ray reflectivity, X-ray diffraction, and atomic force microscopy. We observed a significant improvement in the thermal stability of ALD-modified molecules, with the existence of a supramolecular packing structure up to 500 °C. Following the experimental observations, density functional theory (DFT) calculations indicate the possibility of formation of a covalent network with aluminum atoms connecting OPA molecules at terrace surfaces. Chemical stability is also achieved on top of such a composite surface, inhibiting further ALD oxide deposition. On the other hand, in the terrace edges, where the covalent array is discontinued, the chemical conditions allow for oxide growth. Analysis of the DFT results on band structure and density of states of modified OPA molecules suggests that besides the observed thermal resilience, the dielectric character of OPA layers is preserved. This new ALD-modified OPA composite is potentially suitable for applications such as dielectric layers in organic devices, where better thermal performance is required.