Bioactivity of cerium dioxide nanoparticles as a function of size and surface features.

Nano-dispersed cerium dioxide is promising for use in medicine due to its unique physicochemical properties, including low toxicity, the safety of in vivo usage, active participation in different redox processes occurring in living cells, and its regenerative potential, manifested in the ability of CeO2 to participate repeatedly in redox reactions. In this work, we examined the biological activity of cerium dioxide nanoparticles (CeO2 NPs) synthesized by precipitation in mixed water/alcohol solutions at a constant pH of 9. This synthesis method allowed controlling the size and Ce3+/Ce4+ proportion on the surface of NPs, changing the synthesis conditions and obtaining highly stable suspensions of "naked" CeO2 NPs. Changes in the surface properties upon contact of CeO2 NPs with protein-rich media, e.g., bovine serum albumin and DMEM cell culture medium supplemented with 10% fetal bovine serum, the characteristics of nanoparticle uptake by mouse aortic endothelial cells and the antioxidant activity of the nanoparticles of different sizes were investigated by various state-of-the-art analytical methods.

Exploring the effect of photobiomodulation and gamma visual stimulation induced by 808 nm and visible LED in Alzheimer's disease mouse model.

Although photobiomodulation (PBM) and gamma visual stimulatqion (GVS) have been overwhelmingly explored in the recent time as a possible light stimulation (LS) means of Alzheimer's disease (AD) therapy, their effects have not been assessed at once. In our research, the AD mouse model was stimulated using light with various parameters [continuous wave (PBM) or 40 Hz pulsed visible LED (GVS) or 40 Hz pulsed 808 nm LED (PBM and GVS treatment)]]. The brain slices collected from the LS treated AD model mice were evaluated using (i) fluorescence microscopy to image thioflavine-S labeled amy-loid-ß (Aß) plaques (the main hallmark of AD), or (ii) two-photon excited fluorescence (TPEF) imaging of unlabeled Aß plaques, showing that the amount of Aß plaques was reduced after LS treatment. The imaging results correlated well with the results of Morris water maze (MWM) test, which demonstrated that the spatial learning and memory abilities of LS treated mice were noticeably higher than those of untreated mice. The LS effect was also assessed by in vivo nonlinear optical imaging, revealing that the cerebral amyloid angiopathy decreased spe-cifically as a result of 40 Hz pulsed 808 nm irradiation, on the contrary, the angiopathy reversed after visible 40 Hz pulsed light treatment. The obtained results provide useful reference for further optimization of the LS (PBM or GVS) parameters to achieve efficient phototherapy of AD.

Human mesenchymal stem cells increase LLC metastasis and stimulate or decelerate tumor development depending on injection method and cell amount.

Mesenchymal stem cells (MSCs) being injected into the body can stimulate or decelerate carcinogenesis. Here, the direction of influence of human placenta-derived MSCs (P-MSCs) on the Lewis lung carcinoma (LLC) tumor development and metastatic potential is investigated in C57BL/6 mice depending on the injection method. After intramuscular co-inoculation of LLC and P-MSCs (LLC + P-MSCs), the growth of primary tumor and angiogenesis are slowed down compared to the control LLC on the 15th day. This is explained by the fact of a decrease in the secretion of proangiogenic factors during in vitro co-cultivation of an equal amount of LLC and P-MSCs. When P-MSCs are intravenously (i.v.) injected in the mice with developing LLC (LLC + P-MSCs(i.v.)), the tumor growth and angiogenesis are stimulated on the 15th day. A highly activated secretion of proangiogenic factors by P-MSCs in a similar in vitro model can explain this. In both the models compared to the control on the 23rd day, there is no significant difference in the tumor growth, while angiogenesis remains correspondingly decelerated or stimulated. However, in both the models, the total volume and number of lung metastases constantly increase compared to the control: it is mainly due to small-size metastases for LLC + P-MSCs(i.v.) and larger ones for LLC + P-MSCs. The increase in the rate of LLC cell dissemination after the injection of P-MSCs is explained by the disordered polyploidy and chromosomal instability, leading to an increase in migration and invasion of cancer cells. After LLC + P-MSCs co-inoculation, the tumor cell karyotype has the most complex and heterogeneous chromosomal structure. These findings indicate a bidirectional effect of P-MSCs on the growth of LLC in the early periods after injection, depending on the injection method, and, correspondingly, the number of contacting cells. However, regardless of the injection method, P-MSCs are shown to increase LLC aggressiveness related to cancer-associated angiogenesis and metastasis activation in the long term.

Hyperspectral imaging of lipids in biological tissues using near-infrared and shortwave infrared transmission mode: A pilot study.

Label-free hyperspectral imaging (HSI) of lipids was demonstrated in the near-infrared (NIR) and shortwave infrared (SWIR) regions (950-1800 nm) using porcine tissue. HSI was performed in the transmission light-pass configuration, using a NIR-SWIR camera coupled with a liquid crystal tunable filter. The transmittance spectra of the regions of interest (ROIs), which correspond to the lipid and muscle areas in the specimen, were utilized for the spectrum unmixing. The transmittance spectra in ROIs were compared with those recorded by a spectrophotometer using samples of adipose and muscle. The lipid optical absorption bands at 1210 and 1730 nm were first used for the unmixing and mapping. Then, we performed the continuous multiband unmixing over the entire available spectral range, thereby, considering a combination of characteristic absorption bands of lipids, proteins, and water. The enhanced protocol demonstrates the ability to visualize small adipose inclusions of 1-10 µm size.

Comparing the Impact of NIR, Visible and UV Light on ROS Upregulation via Photoacceptors of Mitochondrial Complexes in Normal, Immune and Cancer Cells.

The effect of UV/visible/NIR light (380/450/530/650/808/1064 nm) on ROS generation, mitochondrial activity and viability is experimentally compared in human neuroblastoma cancer cells. The absorption of photons by mitochondrial photoacceptors in Complexes I, III and IV is in detail investigated by sequential blocking with selective pharmaceutical blockers. Complex I absorbs UV/blue light by heme P450, resulting in a very high rate (14 times) of ROS generation leading to cell death. Complex III absorbs green light, by cytochromes b, c1 and c, and possesses less ability for ROS production (seven times), so that only irradiation lower than 10 mW cm-2 causes an increase in cell viability. Complex IV is well-known as the primary photoacceptor for red/NIR light. Light of 650/808 nm at 10-100 mW cm-2 generates a physiological ROS level about 20% of a basal concentration, which enhance mitochondrial activity and cell survival, while 1064 nm light does not show any distinguished effects. Further, ROS generation induced by low-intensity red/NIR light is compared in neurons, immune and cancer cells. Red light seems to more rapidly stimulate ROS production, mitochondrial activity and cell survival than 808 nm. At the same time, different cell lines demonstrate slightly various rates of ROS generation, peculiar to their cellular physiology.

Near-infrared light reduces ß-amyloid-stimulated microglial toxicity and enhances survival of neurons: mechanisms of light therapy for Alzheimer's disease.

BACKGROUND: Low-intensity light can decelerate neurodegenerative disease progression and reduce amyloid ß (Aß) levels in the cortex, though the cellular and molecular mechanisms by which photobiomodulation (PBM) protects against neurodegeneration are still in the early stages. Microglia cells play a key role in the pathology of Alzheimer's disease by causing chronic inflammation. We present new results concerning the PBM of both oxidative stress and microglia metabolism associated with the activation of metabolic processes by 808 nm near-infrared light. METHODS: The studies were carried out using healthy male mice to obtain the microglial cell suspension from the hippocampus. Oligomeric ß-amyloid (1-42) was prepared and used to treat microglia cells. Light irradiation of cells was performed using diode lasers emitting at 808 nm (30 mW/cm2 for 5 min, resulting in a dose of 10 J/cm2). Mitochondrial membrane potential, ROS level studies, cell viability, apoptosis, and necrosis assays were performed using epifluorescence microscopy. Phagocytosis, nitric oxide and H2O2 production, arginase, and glucose 6-phosphate dehydrogenase activities were measured using standard assays. Cytokines, glucose, lactate, and ATP were measurements with ELISA. As our data were normally distributed, two-way ANOVA test was used. RESULTS: The light induces a metabolic shift from glycolysis to mitochondrial activity in pro-inflammatory microglia affected by oligomeric Aß. Thereby, the level of anti-inflammatory microglia increases. This process is accompanied by a decrease in pro-inflammatory cytokines and an activation of phagocytosis. Light exposure decreases the Aß-induced activity of glucose-6-phosphate dehydrogenase, an enzyme that regulates the rate of the pentose phosphate pathway, which activates nicotinamide adenine dinucleotide phosphate oxidases to further produce ROS. During co-cultivation of neurons with microglia, light prevents the death of neurons, which is caused by ROS produced by Aß-altered microglia. CONCLUSIONS: These original data clarify reasons for how PBM protects against neurodegeneration and support the use of light for therapeutic research in the treatment of Alzheimer's disease.

Red and near infrared light-stimulated angiogenesis mediated via Ca2+ influx, VEGF production and NO synthesis in endothelial cells in macrophage or malignant environments.

Irradiation with red or near-infrared (NIR) light in low level light therapy (LLLT) is found to stimulate cellular processes and bioenergetics, resulting in enhanced wound healing, pain control, neurodegenerative diseases treatment, etc. During light irradiation of tissues and organs, different cells are affected, though the connection between photostimulation of cells and their environmental conditions remains poorly understood. In this report, red/NIR light-stimulated angiogenesis is investigated using endothelial cells in vitro, with a focus on the capillary-like structure (CLS) formation and the respective biochemical processes in cells under conditions proximate to a healthy or malignant environment, which strongly defines angiogenesis. To model environmental conditions for endotheliocytes in vitro, the cell culture environment was supplemented by an augmented conditioned medium from macrophages or cancer cells. The biochemical processes in endothelial cell cultures were investigated with and without irradiation by red (650 nm) and near-infrared (808 nm) laser diodes and under normoxia or hypoxia conditions. A light-stimulated angiogenesis has been found, with a more efficient stimulation by 650 nm light compared to 808 nm light. It was shown that the irradiation with light promoted extracellular Ca2+ influx, fostered cell cycle progression, proliferation and NO generation in endothelial cells, and caused an increase in vascular endothelial growth factor (VEGF) production by endothelial cells and M2 macrophages under hypoxia conditions. The activation of VEGF production by macrophages was found to be associated with an increase in the number of M2 macrophages after light irradiation under hypoxia conditions. Thus, a new pathway of an activation of the endothelial cell metabolism, which is related with the extracellular Ca2+ influx after light irradiation, has been revealed. STATEMENT OF SIGNIFICANCE: Red/NIR light-stimulated angiogenesis has been studied using endothelial cells in vitro, with focus on CLS formation and the respective biochemical processes in cell models proximate to a healthy or malignant environment. A light-stimulated angiogenesis has been found, stimulated via extracellular Ca2+ influx, cell cycle progression, proliferation and NO generation, VEGF production increase by endothelial cells under hypoxia conditions.

NMDA receptor expression during cell transformation process at early stages of liver cancer in rodent models.

Hepatocellular carcinoma (HCC) is the most common primary liver cancer, which is not sensitive to radiotherapy and chemotherapy and very often experiences postoperative relapse. In this regard, effective screening of liver cancer is considered as the most important and urgent task. The aim of our study was to determine whether N-methyl-D-aspartate receptor (NMDAR) and, in particular, its subunits, can serve as biomarkers to distinguish the precancerous liver at early stages of liver fibrosis. We assessed the development of HCC after 10, 15, and 22 wk using a HCC rat model. The expression of NMDAR subunits was monitored at different stages of HCC by means of immunohistochemistry combined with epifluorescence microscopy imaging, Western blotting, and direct bisulfite sequencing. NMDAR subunits were not found in healthy liver tissues. In contrast, NMDAR subunits, in particular NR1 and NR2B, appeared at the stage of severe liver fibrosis (precancerous liver disease) in rats and were expressed during the development of HCC in rats and mice. Using the direct bisulfite sequencing, we detected that increased expression of NMDAR directly correlated with the demethylation of CpG islands in the promoter region of genes encoding receptor subunits. The obtained results confirmed that NMDAR subunits can serve as new biomarkers of precancerous liver disease, severe fibrosis, and its progression towards HCC.NEW & NOTEWORTHY We have shown NMDAR expression in cell transformation process at early stages of cancer, specifically HCC. The aim of our study was to define the disease stages from precancerous liver disease towards liver cancer progression when NMDAR subunits were expressed/detected. A fibrosis/HCC rat model, immunohistochemistry combined with epifluorescence microscopy imaging, Western blotting was used. The dynamics of appearance of NMDAR subunits, their expression and methylation status during the development of HCC were shown and discussed.

Macrophages Modulated by Red/NIR Light: Phagocytosis, Cytokines, Mitochondrial Activity, Ca2+ Influx, Membrane Depolarization and Viability.

Low-level light therapy (LLLT) is emerging as a promising therapeutic approach to modulate the biochemical and molecular processes within living cells. LLLT is known to produce local and systemic effects; therefore, immune cells in local tissues or in the circulation are affected by light. However, this specific effect remains weakly explored. In this study, the effect of red (650 nm) and NIR (808 nm) light on phagocytosis (respiratory burst), cytokine expression, mitochondrial activity, ROS generation, Ca2+ influx and membrane depolarization in macrophages in vitro is investigated. Both the phagocytic capacity and adhesion of macrophages strongly (~2.5 times) increased in the first hours after exposure to light in a dose-dependent manner. The light-evoked upregulation of phagocytosis is found to be less efficient than the maximal pharmacologically induced enhancement of ~3.2 times. Also, red/NIR light reduces the production of pro-inflammatory cytokines and activates the secretion of anti-inflammatory cytokines by several times in activated macrophages. At the same time, the viability shows a biphasic dose response: it increases after irradiation with lower doses (0.3-1 J cm-2 ) and decreases after treatment with higher doses (18-30 J cm-2 ), which is apparently associated with the upregulation of ROS generation, followed by an increase in the mitochondrial activity.

Red and near-infrared light evokes Ca2+ influx, endoplasmic reticulum release and membrane depolarization in neurons and cancer cells.

Low level light therapy uses light of specific wavelengths in red and near-infrared spectral range to treat various pathological conditions. This light is able to modulate biochemical cascade reactions in cells that can have important health implications. In this study, the effect of low intensity light at 650, 808 and 1064 nm on neurons and two types of cancer cells (neuroblastoma and HeLa) is reported, with focus on the photoinduced change of intracellular level of Ca2+ ions and corresponding signaling pathways. The obtained results show that 650 and 808 nm light promotes intracellular Ca2+ elevation regardless of cell type, but with different dynamics due to the specificities of Ca2+ regulation in neurons and cancer cells. Two origins responsible for Ca2+ elevation are determined to be: influx of exogenous Ca2+ ions into cells and Ca2+ release from endoplasmic reticulum. Our investigation of the related cellular processes shows that light-induced membrane depolarization is distinctly involved in the mechanism of Ca2+ influx. Ca2+ release from endoplasmic reticulum activated by reactive oxygen species generation is considered as a possible light-dependent signaling pathway. In contrast to the irradiation with 650 and 808 nm light, no effects are observed under 1064 nm irradiation. We believe that the obtained insights are of high significance and can be useful for the development of drug-free phototherapy.

Laser-Induced Periodic Ag Surface Structure with Au Nanorods Plasmonic Nanocavity Metasurface for Strong Enhancement of Adenosine Nucleotide Label-Free Photoluminescence Imaging.

The label-free detection of biomolecules by means of fluorescence spectroscopy and imaging is topical. The developed surface-enhanced fluorescence technique has been applied to achieve progress in the label-free detection of biomolecules including deoxyribonucleic acid (DNA) bases. In this study, the effect of a strong enhancement of photoluminescence of 5'-deoxyadenosine-monophosphate (dAMP) by the plasmonic nanocavity metasurface composed of the silver femtosecond laser-induced periodic surface structure (LIPSS) and gold nanorods or nanospheres has been realized at room temperature. The highest value of 1220 for dAMP on the Ag-LIPSS/Au nanorod metasurface has been explained to be a result of the synergetic effect of the generation of hot spots near the sharp edges of LIPSS and Au nanorod tips together with the excitation of collective gap mode of the cavity due to strong near-field plasmonic coupling. A stronger plasmonic enhancement of the phosphorescence compared to the fluorescence is achieved due to a greater overlap of the phosphorescence spectrum with the surface plasmon spectral region. The photoluminescence imaging of dAMP on the metasurfaces shows a high intensity in the blue range. The comparison of Ag-LIPSS/Au nanorod and Ag-LIPSS/Au-nanosphere metasurfaces shows a considerably higher enhancement for the metasurface containing Au nanorods. Thus, the hybrid cavity metasurfaces containing metal LIPSS and nonspherical metal nanoparticles with sharp edges are promising for high-sensitive label-free detection and imaging of biomolecules at room temperature.

Defect influence on in-plane photocurrent of InAs/InGaAs quantum dot array: long-term electron trapping and Coulomb screening.

Metamorphic InAs/In0.15Ga0.85As and InAs/In0.31Ga0.69As quantum dot (QD) arrays are known to be photosensitive in the telecommunication ranges at 1.3 and 1.55 µm, respectively; however, for photonic applications of these nanostructures, the effect of levels related to defects still needs in-depth investigation. We have focused on the influence of electron traps of defects on photocurrent (PC) in the plane of the QD array, studying by PC and deep level thermally stimulated current spectroscopy together with HRTEM and theoretical modeling. In the structures, a rich spectrum of electron trap levels of point defects EL6 (E c - 0.37 eV), EL7 (0.29-0.30 eV), EL8 (0.27 eV), EL9/M2 (0.22-0.23 eV), EL10/M1 (0.16 eV), M0 (∼0.11 eV) and three extended defects ED1/EL3 (0.52-0.54), ED2/EL4 (0.47-0.48 eV), ED3/EL5 (0.42-0.43 eV) has been identified. Among them, new defect levels undiscovered earlier in InAs/InGaAs nanostructures has been detected, in particular, EL8 and M0. The found electron traps are shown to affect a time-dependent PC at low temperatures. Besides a long-term kinetics due to trap charging, a prolonged PC decrement versus time is measured under constant illumination. The decrement is interpreted to be related to a Coulomb screening of the conductivity channel by the electrons captured in the QD interface traps. The decrement is well fitted by allometric exponents, which means many types of traps involved in electron capturing. This study provides new findings into the mechanism of in-plane PC of QD arrays, showing a crucial importance of growth-related defects on photoresponsivity at low temperatures.

Red and near-infrared light induces intracellular Ca2+ flux via the activation of glutamate N-methyl-D-aspartate receptors.

Red and near-infrared (NIR) light effect on Ca2+ ions flux through the influence on N-methyl-D-aspartate receptors (NMDARs) and their functioning in HeLa cells was studied in vitro. Cells were irradiated by 650 and 808 nm laser light at different power densities and doses and the obtained effect was compared with that caused by the pharmacological agents. The laser light was found to elevate Ca2+ influx into cell cytoplasm in a dose-dependent manner without changes of the NMDAR functioning. Furthermore, the light of both wavelengths demonstrated the ability to elevate Ca2+ influx under the pharmacological blockade of NMDARs and also might partially abolish the blockade enhancing Ca2+ influx after selective stimulation of the receptors with NMDA. Simultaneously, the light at moderate doses demonstrated a photobiostimulating effect on cells. Based on our experiments and data reported in the literature, we suggest that the low-power visible and NIR light can instigate a cell membrane depolarization via nonthermal activation, resulting in the fast induction of Ca2+ influx into cells. The obtained results also demonstrate that NIR light can be used for nonthermal and nonpharmacological stimulation of NMDARs in cancer cells.

Morpho-Functional Characteristics of Bone Marrow Multipotent Mesenchymal Stromal Cells after Activation or Inhibition of Epidermal Growth Factor and Toll-Like Receptors or Treatment with DNA Intercalator Cisplatin.

This study is aimed to reveal morphological and functional changes in multipotent mesenchymal stromal cells (MSCs) isolated from the rat bone marrow after: (i) activation of Toll-like receptors (TLRs) with teichoic acid (TA), (ii) impact on epidermal growth factor (EGF) receptors with activator EGF or inhibitor Herceptin, and (iii) treatment with DNA intercalator Cisplatin. According to our results, TA and EGF cause an increase in the synthesis of glycosaminoglycans, c-Myc content, and protein in the MSC cytoplasm. It was observed that the cell population in G0 phase decreased and the cell population in G1 phase increased, when compared with control. At the same time, the cell population with a higher nuclear-cytoplasmic ratio (NCR) in S and G2 phases also increased. This indicates the manifestation of the MSC mesenchymal phenotype, exhibiting indirect metabolic signs of the regenerative potential increase. In other experiments, Herceptin was shown to suppress only the stemness signs of MSCs, while Cisplatin seriously affected cell viability in general, reducing synthetic and proliferative activities and causing cell morphology disturbances. © 2018 International Society for Advancement of Cytometry.

Optical windows for head tissues in near-infrared and short-wave infrared regions: Approaching transcranial light applications.

Optical properties of the rat head tissues (brain cortex, cranial bone and scalp skin) are assessed, aiming at transcranial light applications such as optical imaging and phototherapy. The spectral measurements are carried out over the wide spectral range of 350 to 2800 nm, involving visible, near-infrared (NIR) and short-wave infrared (SWIR) regions. Four tissue transparency windows are considered: ~700 to 1000 nm (NIR-I), ~1000 to 1350 nm (NIR-II), ~1550 to 1870 nm (NIR-III or SWIR) and ~2100 to 2300 nm (SWIR-II). The values of attenuation coefficient and total attenuation length are determined for all windows and tissue types. The spectra indicate transmittance peaks in NIR, NIR-II and SWIR-II, with maximum tissue permeability for SWIR light. The use of SWIR-II window for the transcranial light applications is substantiated. Furthermore, absorbance of the head tissues is investigated in details, by defining and describing the characteristic absorption peaks in NIR-SWIR.

Peripheral N-methyl-D-aspartate receptor localization and role in gastric acid secretion regulation: immunofluorescence and pharmacological studies.

The enteric nervous system (ENS) and a glutamate receptor (GluR), N-methyl-D-aspartate receptor (NMDAR), participate in gastric acid secretion (GAS) regulation. NMDARs are localized in different stomach cells; however, knowledge of NMDAR expression and function in the ENS is limited. In the present study, we clarified the types of stomach cells that express the NMDARs that are involved in GAS regulation. The pharmacological method of isolated stomach perfusion by Ghosh and Shild combined with direct mapping of NMDARs by fluorescence microscopy in the rat stomach was employed. By immunofluorescence labeling with an anti-NMDA-NR1 antibody, NMDARs were found to be highly expressed in nerve cells of the submucosal and myenteric plexuses in the stomach. The exact localization of the NMDARs relevant to GAS and its mechanism of action were determined by stimulating different receptors of neuronal and stomach cells using specific secretagogues for NMDA and by selectively blocking those receptors. NMDARs relevant to GAS stimulation are mainly localized in cholinergic interneurons; however, all of the nerve cells of the submucosal ganglia are involved in the stimulating process. In addition, the NMDARs in parietal cells are involved in gastric acid inhibition via influencing H2-histamine receptors.

Interband Photoconductivity of Metamorphic InAs/InGaAs Quantum Dots in the 1.3-1.55-µm Window.

Photoelectric properties of the metamorphic InAs/In x Ga1 - xAs quantum dot (QD) nanostructures were studied at room temperature, employing photoconductivity (PC) and photoluminescence spectroscopies, electrical measurements, and theoretical modeling. Four samples with different stoichiometry of In x Ga1 - xAs cladding layer have been grown: indium content x was 0.15, 0.24, 0.28, and 0.31. InAs/In0.15Ga0.85As QD structure was found to be photosensitive in the telecom range at 1.3 µm. As x increases, a redshift was observed for all the samples, the structure with x = 0.31 was found to be sensitive near 1.55 µm, i.e., at the third telecommunication window. Simultaneously, only a slight decrease in the QD PC was recorded for increasing x, thus confirming a good photoresponse comparable with the one of In0.15Ga0.75As structures and of GaAs-based QD nanostructures. Also, the PC reduction correlate with the similar reduction of photoluminescence intensity. By simulating theoretically the quantum energy system and carrier localization in QDs, we gained insight into the PC mechanism and were able to suggest reasons for the photocurrent reduction, by associating them with peculiar behavior of defects in such a type of structures. All this implies that metamorphic QDs with a high x are valid structures for optoelectronic infrared light-sensitive devices.

Novel Hybrid Compound 4-[(E)-2-phenylethenesulfonamido]-N-hydroxybutanamide with Antimetastatic and Cytotoxic Action: Synthesis and Anticancer Screening.

BACKGROUND: One of the most promising strategies to develop multi-targeted anticancer therapeutics is to introduce to the structure of a potential drug two or more pharmacophores (functional groups or structural fragments), which have antiproliferative, proapoptotic or antimetastatic properties acting via different mechanisms. OBJECTIVE: To design, synthesize and perform screening of a novel hybrid anticancer compound. METHOD: A novel hybrid compound 4-[(E)-2-phenylethenesulfonamido]-N-hydroxybutanamide, combining butanehydroxamate and styrenesulfonamide moieties, was designed, synthesized and investigated as a potent antimetastatic and antiproliferative agent. The structure and purity of the synthesized compound were confirmed by 1H NMR, 13C NMR, LC/MS spectroscopy and elemental analysis. The compound was screened for the anticancer activity in vitro against HeLa and in vivo against Lewis lung carcinoma tumor, using an antitumor metalloenzyme inhibitor GM6001 (Ilomastat, Galardin) and Pifithrin-µ as control anticancer agents. RESULTS: It was found that the application of our compound resulted in a high fraction of apoptotic cells in the cell population, along with disruption in the cell cycle profile manifested as arrest of proliferative phases. Furthermore, changes of the morphological properties (i.e., an enhancement of adhesive properties and reduction of the nuclear-to-cytoplasm ratio) were found. The in vivo screening revealed that the compound significantly inhibited the metastasizing process that was manifested by a reduction in the number and volume of metastases. CONCLUSIONS: The obtained results demonstrate that our compound can serve as a base for further structure optimization in order to design new highly-effective antimetastatic and antitumor agents.

Bipolar Effects in Photovoltage of Metamorphic InAs/InGaAs/GaAs Quantum Dot Heterostructures: Characterization and Design Solutions for Light-Sensitive Devices.

The bipolar effect of GaAs substrate and nearby layers on photovoltage of vertical metamorphic InAs/InGaAs in comparison with pseudomorphic (conventional) InAs/GaAs quantum dot (QD) structures were studied. Both metamorphic and pseudomorphic structures were grown by molecular beam epitaxy, using bottom contacts at either the grown n +-buffers or the GaAs substrate. The features related to QDs, wetting layers, and buffers have been identified in the photoelectric spectra of both the buffer-contacted structures, whereas the spectra of substrate-contacted samples showed the additional onset attributed to EL2 defect centers. The substrate-contacted samples demonstrated bipolar photovoltage; this was suggested to take place as a result of the competition between components related to QDs and their cladding layers with the substrate-related defects and deepest grown layer. No direct substrate effects were found in the spectra of the buffer-contacted structures. However, a notable negative influence of the n +-GaAs buffer layer on the photovoltage and photoconductivity signal was observed in the InAs/InGaAs structure. Analyzing the obtained results and the performed calculations, we have been able to provide insights on the design of metamorphic QD structures, which can be useful for the development of novel efficient photonic devices.

Comparative Study of Photoelectric Properties of Metamorphic InAs/InGaAs and InAs/GaAs Quantum Dot Structures.

Optical and photoelectric properties of metamorphic InAs/InGaAs and conventional pseudomorphic InAs/GaAs quantum dot (QD) structures were studied. We used two different electrical contact configurations that allowed us to have the current flow (i) only through QDs and embedding layers and (ii) through all the structure, including the GaAs substrate (wafer). Different optical transitions between states of QDs, wetting layers, GaAs or InGaAs buffers, and defect-related centers were studied by means of photovoltage (PV), photoconductivity (PC), photoluminescence (PL), and absorption spectroscopies. It was shown that the use of the InGaAs buffer spectrally shifted the maximum of the QD PL band to 1.3 µm (telecommunication range) without a decrease in the yield. Photosensitivity for the metamorphic QDs was found to be higher than that in GaAs buffer while the photoresponses for both metamorphic and pseudomorphic buffer layers were similar. The mechanisms of PV and PC were discussed for both structures. The dissimilarities in properties of the studied structures are explained in terms of the different design. A critical influence of the defects on the photoelectrical properties of both structures was observed in the spectral range from 0.68 to 1.0 eV for contact configuration (ii), i.e., in the case of electrically active GaAs wafer. No effect of such defects on the photoelectric spectra was found for configuration (i), when the structures were contacted to the top and bottom buffers; only a 0.83 eV feature was observed in the photocurrent spectrum of pseudomorphic structure and interpreted to be related to defects close to InAs/GaAs QDs.