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In this work, an injectable in situ depot-forming lipidic lyotropic liquid crystal (L3C) system is developed to codeliver a precisely synchronized combination of chemotherapeutics intratumorally. The developed L3C system is composed of amphiphilic lipids and surfactants, including monoolein, phosphatidylcholine, tocopherol acetate, and d-α-tocopherol polyethylene glycol 1000 succinate. Owing to its amphiphilic nature, the developed formulation can coaccommodate both hydrophobic and hydrophilic chemotherapeutic moieties simultaneously. The study presents a proof of concept by designing a combination chemotherapy regimen in vitro and demonstrating its in vivo translation using doxorubicin and paclitaxel as model hydrophilic and hydrophobic drug moieties, respectively. The synchronized combination of the two chemotherapeutics with maximum synergistic activity was identified, coloaded in the developed L3C system at predefined stoichiometric ratios, and evaluated for antitumor efficacy in the 4T1 breast tumor model in BALB/c mice. The drug-loaded L3C formulation is a low-viscosity injectable fluid with a lamellar phase that transforms into a hexagonal mesophase depot system upon intratumoral injection. The drug-loaded depot system locally provides sustained intratumoral delivery of the chemotherapeutics combination at their precisely synchronized ratio for over a period of one month. Results demonstrate that the exposure of the tumor to the precisely synchronized intratumoral chemotherapeutics combination via the developed L3C system resulted in significantly higher antitumor activity and reduced cardiotoxicity compared to the unsynchronized combination chemotherapy or the synchronized but uncoordinated drug delivery administered by a conventional intravenous route. These findings demonstrate the potential of the developed L3C system for achieving synchronized codelivery of the chemotherapeutics combination intratumorally and improving the efficacy of combination chemotherapy.
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Doxorrubicina , Cristales Líquidos , Ratones Endogámicos BALB C , Animales , Cristales Líquidos/química , Ratones , Doxorrubicina/química , Doxorrubicina/farmacología , Femenino , Paclitaxel/química , Paclitaxel/farmacología , Paclitaxel/farmacocinética , Línea Celular Tumoral , Humanos , Glicéridos/química , Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Protocolos de Quimioterapia Combinada Antineoplásica/química , Protocolos de Quimioterapia Combinada Antineoplásica/farmacocinética , Antineoplásicos/química , Antineoplásicos/farmacología , Portadores de Fármacos/químicaRESUMEN
Machine learning is becoming a valuable tool in the characterisation and property prediction of liquid crystals. It is thus worthwhile to be aware of the possibilities but also the limitations of current machine learning algorithms. In this study we investigated a phase sequence of isotropic - fluid smecticA - hexatic smectic B - soft crystal CrE - crystalline. This is a sequence of transitions between orthogonal phases, which are expected to be difficult to distinguish, because of only minute changes in order. As expected, strong first order transitions such as the liquid to liquid crystal transition and the crystallisation can be distinguished with high accuracy. It is shown that also the hexatic SmB to soft crystal CrE transition is clearly characterised, which represents the transition from short- to long-range order. Limitations of convolutional neural networks can be observed for the fluid to hexatic SmA to SmB transition, where both phases exhibit short-range ordering.
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In this work, a reversible transformation between torons and cholesteric fingers is realized by continuously changing the pitch through temperature variation of the chiral nematic liquid crystal twist inversion system. By decreasing the pitch, the torons act as seeds from which cholesteric fingers gradually grow. By increasing the pitch, the cholesteric fingers gradually shorten and transform back to the initial state. We find that although the morphology of the torons is severely deformed and cannot be distinguished during the heating-cooling loops, the torons are very well topologically protected and can hardly be destroyed.
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Experimental polarising microscopy texture images of the fluid smectic phases and sub-phases of the classic liquid crystal MHPOBC were classified as paraelectric (SmA*), ferroelectric (SmC*), ferrielectric (SmC1/3*), and antiferroelectric (SmCA*) using convolutional neural networks, CNNs. Two neural network architectures were tested, a sequential convolutional neural network with varying numbers of layers and a simplified inception model with varying number of inception blocks. Both models are successful in binary classifications between different phases as well as classification between all four phases. Optimised architectures for the multi-phase classification achieved accuracies of (84 ± 2)% and (93 ± 1)% for sequential convolutional and inception networks, respectively. The results of this study contribute to the understanding of how CNNs may be used in classifying liquid crystal phases. Especially the inception model is of sufficient accuracy to allow automated characterization of liquid crystal phase sequences and thus opens a path towards an additional method to determine the phases of novel liquid crystals for applications in electro-optics, photonics or sensors. The outlined procedure of supervised machine learning can be applied to practically all liquid crystal phases and materials, provided the infrastructure of training data and computational power is provided.
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As electrically generated solitons in liquid crystals, directrons represent intriguing structures promising extensive application prospects in the areas of microcargo vehicles, microreactors, and logic devices. However, manipulating directrons along elaborate predetermined trajectories still remains to be largely explored. In this work, the strategy of constructing high-resolution periodic alignment fields for directrons via the polarization holography photoalignment technique is presented. The optimum exposure dose for directrons to form over a broad range of electric fields is determined to be 32.4 J cm-2 for the alignment layers with 1 wt% azo dye SD1. Zigzag and fishhook-shaped trajectories of directrons are realized with two orthogonal polarized beams. The resolution for zigzag steering of directrons is evaluated to be approximately 56 µm to 80 µm, about three to four times the length of directrons. These results not only enrich the forms of motion of directrons, but also lay the foundations for customized trajectories of directrons in future developments.
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In this work, thousands of electrically driven dissipative solitons, called directrons, are generated in a chiral nematic liquid crystal. The directrons start with random motions but soon synchronize their motions and self-organize into a two-dimensional hexagonal lattice. The directron lattice moves collectively and forms a hexatic phase. By increasing the applied voltage, the lattice exhibits a first-order hexatic-to-liquid phase transition.
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From the motion of fish and birds, to migrating herds of ungulates, collective motion has attracted people for centuries. Active soft matter exhibits a plethora of emergent dynamic behaviors that mimic those of biological systems. Here we introduce an active system composed of dynamic dissipative solitons, i.e. directrons, which mimics the collective motion of living systems. Although the directrons are inanimate, artificial particle-like solitonic field configurations, they locally align their motions like their biological counterparts. Driven by external electric fields, hundreds of directrons are generated in a chiral nematic film. They start with random motions but self-organize into flocks and synchronize their motions. The directron flocks exhibit rich dynamic behaviors and induce population density fluctuations far larger than those in thermal equilibrium systems. They exhibit "turbulent" swimming patterns manifested by transient vortices and jets. They even distinguish topological defects, heading towards defects of positive topological strength and avoiding negative ones.
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Electricidad , Humanos , Movimiento (Física)RESUMEN
A modular approach to underexplored, unsymmetrical [1]benzothieno[3,2-b][1]benzothiophene (BTBT) scaffolds delivers a library of BTBT materials from readily available coupling partners by combining a transition-metal free Pummerer CH-CH-type cross-coupling and a Newman-Kwart reaction. This effective approach to unsymmetrical BTBT materials has allowed their properties to be studied. In particular, tuning the functional groups on the BTBT scaffold allows the solid-state assembly and molecular orbital energy levels to be modulated. Investigation of the charge transport properties of BTBT-containing small-molecule:polymer blends revealed the importance of molecular ordering during phase segregation and matching the highest occupied molecular orbital energy level with that of the semiconducting polymer binder, polyindacenodithiophene-benzothiadiazole (PIDTBT). The hole mobilities extracted from transistors fabricated using blends of PIDTBT with phenyl or methoxy functionalized unsymmetrical BTBTs were double those measured for devices fabricated using pristine PIDTBT. This study underscores the value of the synthetic methodology in providing a platform from which to study structure-property relationships in an underrepresented family of unsymmetrical BTBT molecular semiconductors.
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To address the need for localized chemotherapy against unresectable solid tumors, an injectable in situ depot-forming lipidic lyotropic liquid crystal system (L3CS) is explored that can provide spatiotemporal control over drug delivery. Although liquid crystals have been studied extensively before but their application as an injectable intratumoral depot system for locoregional chemotherapy has not been explored yet. The developed L3CS in the present study is a low-viscosity injectable fluid having a lamellar phase, which transforms into a hexagonal mesophase depot system on subcutaneous or intratumoral injection. The transformed depot system can be preprogrammed to provide tailored drug release intratumorally, over a period of one week to one month. To establish the efficacy of the developed L3CS, doxorubicin is used as a model drug. The drug release mechanism is studied in detail both in vitro and in vivo, and the efficacy of the developed system is investigated in the murine 4T1 tumor model. The direct intratumoral injection of the L3CS provided localized delivery of doxorubicin inside the tumor and restricted its access within the tumor only for a sustained period of time. This led to an over 10-fold reduction in tumor burden, reduced cardiotoxicity, and a significant increase in the median survival rate, compared to the control group. The developed L3CS thus provides an efficient strategy for localized chemotherapy against unresectable solid tumors with a great degree of spatial and temporal control over drug delivery.
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Cristales Líquidos , Animales , Cardiotoxicidad , Doxorrubicina , Liberación de Fármacos , Lípidos , RatonesRESUMEN
Despite the development of the brilliant flat-panel TVs and computer screens that we all use on a daily basis, liquid crystals are far from being exhausted as a topic of research. Novel effects, new, modern, self-organized materials, and a range of applications are being developed, which are on the borderline between nanotechnology and soft condensed matter, and which use liquid crystals as a vehicle to study fundamental physical questions, all the way to mimicking nature and life. In this perspective article we will introduce an illustrative example, which will draw on a range of non-display aspects in liquid crystal research which have increasingly gained interest over the past years, namely self-organization of liquid crystals, colloidal ordering of magnetic nanoparticles, topological defects, and biological structures.
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Zoledronic acid (ZOL) is a third generation bisphosphonate which can be used as a drug for the treatment of osteoporosis and metastasis. In this study, graphene oxide (GO) is conjugated with ZOL, and the nanostructured material is evaluated in terms viability, proliferation and differentiation. Furthermore, the associated morphological changes of bone marrow-derived mesenchymal stem cells (BM-MSC), and Michigan Cancer Foundation-7 (MCF-7) breast cancer cells, as well as the effect of the drugs on mineralization of BM-MSCs are investigated using a variety of characterization techniques including Fourier Transform Infrared Spectroscopy (FTIR), scanning electron microscopy (SEM) as well as alamar blue, acridine orange, and alizarin red assays. Nanostructured ZOL-GO with an optimum performance is synthesized using ZOL and GO suspensions with the concentration of 50 µM and 2.91 ng/ml, respectively. ZOL-GO nanostructures can facilitate the mineralization of BM-MSC cells, demonstrated by the formation of clusters around the cells. The results obtained confirm the performance of ZOL-GO nanostructures as promising drug complexes for the treatment of osteoporosis and metastasis.
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Neoplasias de la Mama/tratamiento farmacológico , Grafito/farmacología , Nanoestructuras/química , Osteoporosis/tratamiento farmacológico , Ácido Zoledrónico/farmacología , Neoplasias de la Mama/patología , Diferenciación Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Femenino , Grafito/química , Humanos , Células MCF-7 , Metástasis de la Neoplasia , Osteoporosis/patología , Ácido Zoledrónico/químicaRESUMEN
Electric field induced instabilities of nematic molecules are of importance for both fundamental science and practical applications. Complex electro-hydrodynamic (EHD) effects such as electro-convection, fingerprint textures, spatiotemporal chaos, and solitons in nematics have been broadly investigated and generated much attention. In this work, dissipative solitons as a novel EHD phenomenon are realized in nematics with positive anisotropies, presumably for the first time. Unlike the ones reported recently in nematics with negative anisotropies whose formation and dynamics are mainly attributed to the flexoelectric and electro-convection effects, the solitons discussed here arise from the nonlinear coupling between the director field and the isotropic flow induced by ion motion. The structure and dynamics of the solitons are demonstrated and the influences of chirality, azimuthal anchoring and ion concentration are also investigated. Finally, we show that the propagation trajectory of solitons can be manipulated by patterned photoalignment and micro-particles can be trapped by them as vehicles for micro-cargo transport.
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The thermal stabilization of blue phases is a subject that has been of scientific and technological interest since their discovery. Meanwhile, carbonaceous nanomaterials such as C60 fullerenes, carbon nanotubes and graphene have generated interdisciplinary interest spanning across solid-state physics, organic chemistry, colloids, all the way to soft matter physics. Herein, the stabilization of liquid crystal blue phases by doping with C60, single-walled carbon nanotubes and graphene oxide is described. All three types of particles are found to extend the combined temperature range of blue phases I and II by a factor of â¼5. Furthermore, mixtures of pairs of different materials, and all three types are shown to stabilize the blue phases. The temperature range of the blue phases is shown to grow at the expense of the cholesteric phase. This leads to a blue phase-cholesteric-smecticA phase triple-point in all cases except that of doping with carbon nanotubes. The mechanisms of this thermal stabilization are discussed in light of theoretical descriptions for other established systems.
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The annihilation dynamics of s = ±1 topological defects with and without microparticles in a nematic liquid crystal were investigated and compared. The microparticle with a homeotropic surface anchoring can act as a s = +1 defect and produce a corresponding s = -1 defect nearby. Both of them attract and move towards each other. The speed of the positive defect induced by the microparticle is much slower than that of the negative defect, contrary to the situation without particles. The effects of electric field strength and frequency, particle size, the confining cell gap, and temperature were systematically investigated. The study shows that the dynamics of the annihilation process is related to a complex interplay between elastic attractions, viscous drag forces, backflow effects, director configurations and cell confinement.
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Due to an oversight during production, the authors wish to make the following correction to reference [65] of this paper [...].
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Liquid crystals are an integral part of a mature display technology, also establishing themselves in other applications, such as spatial light modulators, telecommunication technology, photonics, or sensors, just to name a few of the non-display applications. In recent years, there has been an increasing trend to add various nanomaterials to liquid crystals, which is motivated by several aspects of materials development. (i) addition of nanomaterials can change and thus tune the properties of the liquid crystal; (ii) novel functionalities can be added to the liquid crystal; and (iii) the self-organization of the liquid crystalline state can be exploited to template ordered structures or to transfer order onto dispersed nanomaterials. Much of the research effort has been concentrated on thermotropic systems, which change order as a function of temperature. Here we review the other side of the medal, the formation and properties of ordered, anisotropic fluid phases, liquid crystals, by addition of shape-anisotropic nanomaterials to isotropic liquids. Several classes of materials will be discussed, inorganic and mineral liquid crystals, viruses, nanotubes and nanorods, as well as graphene oxide.
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The application of an electric field to microspheres suspended in a liquid crystal causes particle translation in a plane perpendicular to the applied field direction. Depending on applied electric field amplitude and frequency, a wealth of different motion modes may be observed above a threshold, which can lead to linear, circular, or random particle trajectories. We present the stability diagram for these different translational modes of particles suspended in the isotropic and the chiral nematic phase of a liquid crystal and investigate the angular velocity, circular diameter, and linear velocity as a function of electric field amplitude and frequency. In the isotropic phase a narrow field amplitude-frequency regime is observed to exhibit circular particle motion whose angular velocity increases with applied electric field amplitude but is independent of applied frequency. The diameter of the circular trajectory decreases with field amplitude as well as frequency. In the cholesteric phase linear as well as circular particle motion is observed. The former exhibits an increasing velocity with field amplitude, while decreasing with frequency. For the latter, the angular velocity exhibits an increase with field amplitude and frequency. The rotational sense of the particles on a circular trajectory in the chiral nematic phase is independent of the helicity of the liquid crystalline structure, as is demonstrated by employing a cholesteric twist inversion compound.
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Graphene oxide (GO) forms well ordered liquid crystal (LC) phases in polar solvents. Here, we map the lyotropic phase diagram of GO as a function of the lateral dimensions of the GO flakes, their concentration, geometrical confinement configuration and solvent polarity. GO flakes were prepared in water and transferred into other polar solvents. Polarising optical microscopy (POM) was used to determine the phase evolution through the isotropic-biphasic-nematic transitions of the GO LC. We report that the confinement volume and geometry relative to the particle size is critical for the observation of the lyotropic phase, specifically, this determines the low-end concentration limit for the detection of the GO LC. Additionally, a solvent with higher polarisability stabilises the LC phases at lower concentrations and smaller flake sizes. GO LCs have been proposed for a range of applications from display technologies to conductive fibres, and the behaviour of LC phase formation under confinement imposes a limit on miniaturisation of the dimensions of such GO LC systems which could significantly impact on their potential applications.
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Graphene oxide (GO) flakes of different sizes were prepared and dispersed in isotropic and nematic (anisotropic) fluid media. The dielectric relaxation behaviour of GO-dispersions was examined for a wide temperature (25-60 (o)C) and frequency range (100 Hz-2 MHz). The mixtures containing GO flakes exhibited varying dielectric relaxation processes, depending on the size of the flakes and the elastic properties of the dispersant fluid. Relaxation frequencies of the GO doped isotropic media, such as isopropanol IPA, were observed to be much lower than the GO doped thermotropic nematic medium 5CB. It is anticipated that the slow relaxation frequencies (~10 kHz) could be resulting from the relaxation modes of the GO flakes while the fast relaxation frequencies (~100 kHz) could indicate strongly slowed down molecular modes of the nematogenic molecules, which are anchored to the GO flakes via dispersion interactions. The relaxation frequencies decreased as the size of the GO flakes in the isotropic solvent was increased. Polarizing microscopy showed that GO flakes with a mean diameter of 10 µm, dispersed in water, formed a lyotropic nematic liquid crystal phase. This lyotropic nematic exhibited the slowest dielectric relaxation process, with relaxation frequencies in the order of 2 kHz, as compared to the GO-isotropic suspension and the GO-doped 5CB.