A novel nanoformulation, C60 fullerene loaded with a plant alkaloid Piperlongumine (PL) molecules (C60-PL nanocomplex), as a potential drug for the treatment of highly metastatic lung cancer was created and characterized by using ultrasonic technology, computer simulation, atomic force and scanning tunneling microscopy. The aim of the study was to evaluate the antimetastatic potential of PL alone and the C60-PL nanocomplex using Lewis lung carcinoma (LLC) cell line as a model. Evidence has been obtained that the 2:1C60-PL nanocomplex is a potent agent capable of effectively reducing the survival, migration and invasion of LLC cells in vitro, as well as tumor growth and metastasis in vivo compared to free PL. These effects in cell behavior were shown to be associated with an increased Bax expression and high level of cleaved PARP confirming the proapototic potential of C60-PL nanocomplex as well as down-regulation of the mRNA of epithelial-mesenchymal transition regulator Twist1 and cancer stem cell marker CD44, a reduced level of phosphorylated mTOR and adaptor protein Ruk/CIN85. Histological analysis of the lung tissue of LLC-bearing mice showed that in animals that received the C60-PL nanocomplex, the regression of metastases prevailed over their growth. The obtained results allow to conclude that the proposed C60-PL nanocomplex represents a promising drug for the treatment of metastatic lung cancer.
The development of an effective therapy aimed at restoring muscle dysfunctions in clinical and sports medicine, as well as optimizing working activity in general remains an urgent task today. Modern nanobiotechnologies are able to solve many clinical and social health problems, in particular, they offer new therapeutic approaches using biocompatible and bioavailable nanostructures with specific bioactivity. Therefore, the nanosized carbon molecule, C60 fullerene, as a powerful antioxidant, is very attractive. In this study, a comparative analysis of the dynamic of muscle soleus fatigue processes in rats was conducted using 50 Hz stimulation for 5 s with three consistent pools after intraperitoneal administration of the following antioxidants: C60 fullerene (a daily dose of 1 mg/kg one hour prior to the start of the experiment) and N-acetylcysteine (NAC; a daily dose of 150 mg/kg one hour prior to the start of the experiment) during five days. Changes in the integrated power of muscle contraction, levels of the maximum and minimum contraction force generation, time of reduction of the contraction force by 50% of its maximum value, achievement of the maximum force response, and delay of the beginning of a single contraction force response were analyzed as biomechanical markers of fatigue processes. Levels of creatinine, creatine phosphokinase, lactate, and lactate dehydrogenase, as well as pro- and antioxidant balance (thiobarbituric acid reactive substances, hydrogen peroxide, reduced glutathione, and catalase activity) in the blood of rats were analyzed as biochemical markers of fatigue processes. The obtained data indicate that applied therapeutic drugs have the most significant effects on the 2nd and especially the 3rd stimulation pools. Thus, the application of C60 fullerene has a (50–80)% stronger effect on the resumption of muscle biomechanics after the beginning of fatigue than NAC on the first day of the experiment. There is a clear trend toward a positive change in all studied biochemical parameters by about (12–15)% after therapeutic administration of NAC and by (20–25)% after using C60 fullerene throughout the experiment. These findings demonstrate the promise of using C60 fullerenes as potential therapeutic nanoagents that can reduce or adjust the pathological conditions of the muscular system that occur during fatigue processes in skeletal muscles.
We study the liquid crystalline phase behaviour of the two-component aqueous colloidal suspensions of multiwalled carbon nanotubes (MWCNTs) and rod-like vanadium pentoxide (V2O5) nanoparticles. The phase diagram features a stable nematic phase in a wide range of concentration of solid components. The oriented nematic phase of the two-component suspension was exposed to the action of alternating current electric field. A variation in MWCNTs concentration within 0.01-0.51 wt.% demonstrates a significant increase in the optical response of the system to the applied electric field.
Effective targeting of metastasis is considered the main problem in cancer therapy. The development of herbal alkaloid Berberine (Ber)-based anticancer drugs is limited due to Ber’ low effective concentration, poor membrane permeability, and short plasma half-life. To overcome these limitations, we used Ber noncovalently bound to C60 fullerene (C60). The complexation between C60 and Ber molecules was evidenced with computer simulation. The aim of the present study was to estimate the effect of the free Ber and C60-Ber nanocomplex in a low Ber equivalent concentration on Lewis lung carcinoma cells (LLC) invasion potential, expression of epithelial-to-mesenchymal transition (EMT) markers in vitro, and the ability of cancer cells to form distant lung metastases in vivo in a mice model of LLC. It was shown that in contrast to free Ber its nanocomplex with C60 demonstrated significantly higher efficiency to suppress invasion potential, to downregulate the level of EMT-inducing transcription factors SNAI1, ZEB1, and TWIST1, to unblock expression of epithelial marker E-cadherin, and to repress cancer stem cells-like markers. More importantly, a relatively low dose of C60-Ber nanocomplex was able to suppress lung metastasis in vivo. These findings indicated that сomplexation of natural alkaloid Ber with C60 can be used as an additional therapeutic strategy against aggressive lung cancer.
Lyotropic chromonic liquid crystals (LCLCs) combine a very high packing density (intramolecular separation is about 3.4 Å within aggregates) with an ability to form ordered structures that are transferable from a water solution to a dry film. We show that the electric current in a dry film of LCLC aggregates is sensitive to the distance between the molecules in the aggregates and that it depends on the ambient humidity. Thus, by measuring the electric current through an LCLC film printed onto a substrate with predesigned electrodes and integrated circuits, we can measure the humidity. A humidity sensor based on LCLCs has high sensitivity, a fast response, and short recovery times.
Cisplatin (Cis-Pt) is the cytotoxic agent widely used against tumors of various origin, but its therapeutic efficiency is substantially limited by a non-selective effect and high toxicity. Conjugation of Cis-Pt with nanocarriers is thought to be one option to enable drug targeting. The aim of this study was to estimate toxic effects of the nanocomplex formed by noncovalent interaction of C60 fullerene with Cis-Pt against Lewis lung carcinoma (LLC) cells in comparison with free drug. Scanning tunneling microscopy showed that the minimum size of C60–Cis-Pt nanoparticles in aqueous colloid solution was 1.1 nm whereas that of C60 fullerene was 0.72 nm, thus confirming formation of the nanocomplex. The cytotoxic effect of C60–Cis-Pt nanocomplex against LLC cells was shown to be higher with IC50 values 3.3 and 4.5 times lower at 48 h and 72 h, respectively, as compared to the free drug. 12.5 µM Cis-Pt had no effect on LLC cell viability and morphology while C60–Cis-Pt nanocomplex in Cis-Pt-equivalent concentration substantially decreased the cell viability, impaired their shape and adhesion, inhibited migration and induced accumulation in proapoptotic subG1 phase. Apoptosis induced by the C60–Cis-Pt nanocomplex was confirmed by caspase 3/7 activation and externalization of phosphatidylserine on the outer surface of LLC cells with the double Annexin V-FITC/PI staining. We assume that C60 fullerene as a component of the C60–Cis-Pt nanocomplex promoted Cis-Pt entry and intracellular accumulation thus contributing to intensification of the drug’s toxic effect against lung cancer cells.
Among organic semiconductors, rubrene (C42H28, 5,6,11,12-tetraphenyltetracene, Rub) is extensively studied in recent years, since it exhibits interesting physical properties such as very high charge carrier mobilities in organic field-effect transistors at room temperature. Rub is used as a laser dye and as a fluorescent dopant in other organic light-emitting diodes (OLEDs) to improve the characteristics such as lifetime, stability, color, and brightness. However, there are controversies as to the Rub degradation both in the bulk state and thin layers. So, the better understanding of these phenomena is crucial for improving the performance of organic devices. In this work, we present the results on complex studies of the molecular structure, morphology, and photoluminescence (PL) of Rub layers deposited on freshly cleaved KBr(100) and Au(111) substrates by vacuum thermal evaporation. Additionally, the two-component vacuum deposited (VD) Rub-tetracene (Tc) films were studied. Special attention was paid to the susceptibility of films to the oxidation under ambient conditions. The chemical structure and molecular ordering in the obtained VD thin organic films were evaluated by FTIR spectroscopy, and the structure of the very first Rub layers on atomically smooth Au(111) surfaces was studied with scanning tunneling microscopy (STM). From the changes in the peaks position and the intensity of room-temperature PL spectra of the films with time, the degradation kinetics of the Rub emission is analyzed.
We discovered the phenomenon of liquid crystal (LC) alignment on a photosensitive chalcogenide glass film As20Se80 after irradiation of the LC in the isotropic phase with polarised light. The photoalignment was observed after cooling of the LC to the nematic phase. Quality of the photoalignment depended on an initial phase state of the LC. If the photoalignment was uniform at the irradiation of the isotropic phase of the LC that initially was pre-aligned in the nematic phase, the irradiation of the cell being filled in the isotropic phase resulted in inhomogeneous photoalignment. The orientation of the LC strongly depended on the geometry of the irradiation the LC in the cell. In the case of the direct irradiation of the chalcogenide surface, the photoorientation of the LC was stable. On the contrary, the irradiation of the chalcogenide surface through the LC layer led to the temporal photoalignment that diminished within few days. The results are explained in the frame of the model that suggests two mechanisms of photoalignment. The first one is related to a light-induced anisotropy on chalcogenide layer and the second one involves a LC in the process. We assume that an anisotropic light-induced desorption of LC molecules from the chalcogenide layer is the origin of last kind of photoalignment. The asymmetry of the photoalignment properties at the irradiation from the different sides of the chalcogenide surface is explained by producing different surface structures at the irradiation from the different sides.
The axially-coordinated phthalocyanines were previously reported as agents possessing strong anti-fibrillogenic properties. In the presented study we used the atomic force microscopy to investigate the intermediates and the products of insulin aggregation reaction formed in the presence of Zr and Hf phthalocyanine complexes that contain out-of-plane ligands of different size and nature. It is shown that while phthalocyanine-free insulin generated mostly amyloid fibrils with a diameter of 2-8nm and a length of up to 5μm, the presence of phthalocyanines with spatial bulky ligands (PcZrDbm2) leads to the redirection of the fibrillization reaction to the formation of the spherical oligomer aggregates with a diameter of 4-12nm. At the same time the phthalocyanine complex PcHfCl2 having the small-volume ligands induces the formation of large size insulin aggregates with a height of about 100nm that are supposed to be amorphous species. The study of the aggregation intermediates showed the certain similarity of the reaction passing for phthalocyanine-free insulin and insulin in the presence of PcZrDbm2. The large-size amorphous species were observed at the beginning of reaction, later they dissociated, leading to the formation and growth of the smaller size particles. The amyloid-sensitive cyanine dye 7519 demonstrates the strong fluorescent response both in the presence of fibrils and spherical oligomers, while it is non-sensitive to amorphous aggregates.
The molecular structure, morphology, and electrical conductivity of thin tetracene layers obtained by the thermal vacuum deposition have been studied with the help of FTIR spectroscopy and STM/STS techniques as well. It has been shown that this preparation method does not change the tetracene molecular structure. The tetracene thin layers on the atomically smooth pyrolytic graphite surface demonstrate an amorphous structure. The local current-voltagecharacteristics (CVC) measured for tetracene films ~10 monolayers thick show a well-defined asymmetry relative to a tunnel voltage. A study of the electrical conductivity and the electroluminescence (EL) of a planar composite consisting of gold island films and tetracene layers has revealed that EL from submicron luminescent centers is observed on a superlinear section of conduction current I–V curves. The EL intensity grows with increasing voltage and becomes maximal at the CVC saturation. It is found that the EL from the nanocomposite has a 560-nm wavelength emission maximum.
This article describes the photodynamic inactivation of mosquito iridescent virus (MIV) Aedes flavescens in the presence of water-soluble C-60 fullerenes. It has been observed that the photodynamic inactivation of MIV for about 1 h reduces the infectious titre of the virus in large wax-moth larvae Galleria mellonella to 4.5 lg ID50 /mL. The influence of the C-60 concentration on its anti-viral activity was tested in the concentration range from 1 to 0.001 mg/mL. It has been found that C-60 is able to inactivate the iridovirus even in low concentrations. Consequently, the findings of this work suggest that photoexcited C-60 fullerenes can be successfully used for the inactivation of iridoviruses in biological systems.