Eye orbit effects on eyeball resonant frequencies and acoustic tonometer measurements.

The eye orbit has mechanical and acoustic characteristics that determine resonant frequencies and amplify acoustic signals in certain frequency ranges. These characteristics also interfere with the acoustic amplitudes and frequencies of eyeball when measured with an acoustic tonometer. A model in which a porcine eyeball was embedded in ultrasonic conductive gel in the orbit of a model skull was used to simulate an in vivo environment, and the acoustic responses of eyeballs were detected. The triggering source was a low-power acoustic speaker contacting the occipital bone, and the detector was a high-resolution microphone with a dish detecting the acoustic signals without contacting the cornea. Dozens of ex vivo porcine eyeballs were tested at various intraocular pressure levels to detect their resonant frequencies and acoustic amplitudes in their power spectra. We confirmed that the eyeballs' resonant frequencies were proportional to intraocular pressure, but interference from orbit effects decreased the amplitudes in these resonant frequency ranges. However, we observed that the frequency amplitudes of eyeballs were correlated with intraocular pressure in other frequency ranges. We investigated eye orbit effects and demonstrated how they interfere with the eyeball's resonant frequencies and frequency amplitudes. These results are useful for developing advanced acoustic tonometer.

Effects of Electromagnets on Bovine Corneal Endothelial Cells Treated with Dendrimer Functionalized Magnetic Nanoparticles.

To improve bovine corneal endothelial cell (BCEC) migration, enhance cell energy, and facilitate symmetric cell distribution in corneal surfaces, an electromagnet device was fabricated. Twenty nanometer superparamagnetic iron oxide nanoparticles (SPIONs) functionalized with fourth-generation dendrimer macromolecules were synthesized, and their size and structure were evaluated using transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS), and Fourier transform infrared spectroscopy (FTIR). The results confirmed the configuration of the dendrimer on the SPION surfaces. In vitro biocompatibility was assessed using the 3-[4,5-dimethylthiazol-2yl]-2,5-diphenyl tetrazolium bromide assay. No significant toxicity was noted on BCECs within 24 h of incubation. In the cell migration assay, cells treated with dendrimer-coated SPIONs exhibited a relatively high wound healing rate under sample addition (1 µg/mL) under a magnetic field. Real-time PCR on BCECs treated with dendrimer-coated SPIONs revealed upregulation of specific genes, including AT1P1 and NCAM1, for BCECs-dendrimer-coated SPIONs under a magnetic field. The three-dimensional dispersion of BCECs containing dendrimer-coated SPIONs under a magnetic field was evaluated using COMSOL Multiphysics software. The results revealed the BCECs-SPION vortex pattern layers in the corneal surface corresponded to the electromagnet's displacement from the ocular surface. Magnetic resonance imaging (MRI) indicated that dendrimer-coated SPIONs can be used as a T2 contrast agent.

Polyethylene glycol triggers the anti-cancer impact of curcumin nanoparticles in sw-1736 thyroid cancer cells.

Curcumin has been recognized as an effective anticancer agent. However, due to its hydrophobic property, the cell absorption is not satisfied. Herein, the curcumin nanoparticles were prepared in the presence of polyethylene glycol 6000 (PEG6000) to reduce its elimination by immune system. For first time, not only the curcumin was encapsulated within the niosome nanoparticles modified by PEG, there are no reports related to the anticancer property of curcumin against thyroid cancers. The nanoparticles was developed and its anticancer was studied on sw-1736 cancer cell line. The nanoparticles were examined by scanning electron microscopy (SEM) and dynamic light scattering (DLS). Also, the release profile of curcumin, the IC50 concentration, the radical amount and the gene expression were evaluated. The optimized nanoparticles showed a diameter of 212 ± 31 nm by SEM and the encapsulation efficiency and loading capacity of 76% and 16.8% respectively. DLS confirmed the polydispersity index (PDI) of 0.596 and the release model was shown a sustained release with the delivery of 68% curcumin after 6 days. Also, the nanoparticles indicated the higher storage stability at 4 °C. After the cell treatment, the apoptotic bodies were appeared and IC50 was obtained as 0.159 mM. Moreover, the generated radicals by the treated cells was 86% after 72 h and the gene pattern indicated the bax/bcl2 ratio of 6.83 confirming the apoptosis effect of the nanoparticles. The results approved the nanoparticles could be suggested as an anticancer drug candidate for thyroid cancers. The encapsulated curcumin within the niosome nanoparticles modified with PEG, could be released and up-taken by the thyroid cancer cell line due to the same hydrophobic property of cell membrane and the niosome particles. The reaction between curcumin and cellular components generates radicals and activates the apoptotic pathway. The corresponding reaction finally makes cell death.

Synergic Effect of Novel WS2 Carriers Holding Spherical Cobalt Ferrite @cubic Fe3O4 (WS2/s-CoFe2O4@c-Fe3O4) Nanocomposites in Magnetic Resonance Imaging and Photothermal Therapy for Ocular Treatments and Investigation of Corneal Endothelial Cell Migration.

The design of novel materials to use simultaneously in an ocular system for driven therapeutics and wound healing is still challenging. Here, we produced nanocomposites of tungsten disulfide carriers with spherical cobalt ferrite nanoparticles (NPs) as core inside a cubic iron oxide NPs shell (WS2/s-CoFe2O4@c-Fe3O4). Transmission electron microscopy (TEM) confirmed that 10 nm s-CoFe2O4@c-Fe3O4 NPs were attached on the WS2 sheet surfaces. The cytotoxicity of the WS2 sheets and nanocomposites were evaluated on bovine cornea endothelial cells (BCECs) using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay for a duration of three days. The MTT assay results showed low toxicity of the WS2 sheets on BCECs by 67% cell viability at 100 µg/mL in 24 h, while the nanocomposites show 50% cell viability in the same conditions. The magnetic resonance imaging (MRI) of nanocomposites revealed the excellent T2-weighted imaging with an r2 contrast of 108 mM-1 S-1. The in vitro photothermal therapy based on WS2 sheets and WS2/s-CoFe2O4 @c-Fe3O4 nanocomposites using 808 nm laser showed that the maximum thermal energy dispatched in medium at different applied power densities (1200 mw, 1800, 2200, 2600 mW) was for 0.1 mg/mL of the sample solution. The migration assay of BCECs showed that the wound healing was approximately 20% slower for the cell exposed by nanocomposites compared with the control (no exposed BCECs). We believe that WS2/s-CoFe2O4@c-Fe3O4 nanocomposites have a synergic effect as photothermal therapy agents for eye diseases and could be a target in an ocular system using MRI.

Systems toxicology assessment revealed the impact of graphene-based materials on cell cycle regulators.

Understanding the cellular and molecular toxicity of graphene and its derivatives is essential for their biomedical applications. Herein, gene expression profile of graphene-exposed cells was retrieved from the Gene expression omnibus database. Differentially expressed genes and their functional roles were then investigated through the pathway, protein-protein interaction (PPI) network, and module analysis. High degree (hub) and high betweenness centrality (bottleneck) nodes were subsequently identified. The functional analysis of central genes indicated that these graphene-gene interactions could be of great value for further investigation. Accordingly, we also followed the expression of five hub-bottleneck genes in graphene-treated murine peritoneal macrophages and human breast cancer cell line by real-time PCR. The five hub-bottleneck genes related to graphene cytotoxicity; CDK1, CCNB1, PLK1, TOP2A, and CCNA2 were identified through network analysis, which were highly correlated with regulation of cell cycle processes. The module analysis indicated the cell cycle pathway to be the predominant one. Gene expression evaluation showed downregulation of these genes in the macrophages and cancer cells treated with graphene. These results provided some new intuitions concerning the graphene-cell interactions and unveiled targeting critical cell cycle regulators. The present study indicated some toxic effects of graphene-based materials through systems toxicology assessment. Integrating gene expression and PPI network may help explaining biological responses of graphene and lead to beneficial impacts in nanomedicine.

The biomedical potential of cellulose acetate/polyurethane nanofibrous mats containing reduced graphene oxide/silver nanocomposites and curcumin: Antimicrobial performance and cutaneous wound healing.

In this study, nanofibrous scaffolds were prepared from polyurethane and cellulose acetate using electrospinning. Reduced graphene oxide/silver nanocomposites, rGO/Ag, were also used into the mats due to the strong antibacterial activity of rGO/Ag nanocomposites. In order to prevent the agglomeration of silver nanoparticles, AgNPs, the nanoparticles were decorated onto the reduced graphene oxide (rGO) sheets. Initially, Graphene oxide, briefly GO, was synthesized by the improved Hummer method. Then, nanocomposites of reduced graphene oxide were decorated with Ag and were fabricated via a green and facile hydrothermal method. Thereafter, the scaffold containing rGO/Ag nanocomposites, curcumin or both of them were prepared using the electrospinning method. The obtained scaffolds were characterized by scanning electron microscopy (SEM), contact angle, tensile analysis, porosity, and water vapor transmission rate (WVTR). 3-[4,5-Dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide assay, MTT, confirmed the biocompatibility of the composite nanofibers. The scaffolds were able to hinder both of the Gram-negative and Gram-positive bacteria through direct contact with them. In vivo histopathological studies indicated that the scaffold incorporated rGO/Ag nanocomposites and curcumin has the most effect on wound healing and can promote the healing rate of artificial wounds, which indicates the good biomedical potential of nanomaterial in wound healing.

Photothermal enhancement in sensitivity of lateral flow assays for detection of E-coli O157:H7.

Lateral flow immunoassay (LFA) is a well-known point-of-care technology for the detection of various analytes. However, low sensitivity and lack of quantitative results are some of its critical drawbacks. Here we report a photothermal enhanced lateral flow sensor on the basis of the photothermal properties of reduced graphene oxide (rGO) for the detection of E-coli O157:H7 as a model pathogen. The calibration curve of the photothermal method exhibited a linear range from 5 × 105 to 5 × 107 CFU/ml with a correlation coefficient of R2 = 0.96 and a regression equation of y = 8.1x-43 for standard bacteria solutions in phosphate buffer. The limit of detection was ∼5 × 105 CFU/ml for standard bacteria solutions, which was a 10-fold enhancement in sensitivity compared to the qualitative results. Specificity experiments showed that the photothermal method can only detect the target bacteria among 6 types of bacteria strains. It was confirmed that the developed technique could be a highly potential method for the rapid detection field because it can provide fast quantitative results with improved sensitivity.

Antibacterial properties of nanoporous graphene oxide/cobalt metal organic framework.

Metal-organic framework (MOF) based graphene oxide (GO) recently merits of attention because of the relative correspondence of GO with metal ions and organic binding linkers. Furthermore, introducing the GO to the Co-MOF to make a new nanoporous hybrid have are improved the selectivity and stability of the Co-MOF. Here the graphene oxide/cobalt metal organic framework (GO/Co-MOF) was synthesized by a solvothermal process using cobalt salt and terephthalic acid and used for biocidal activity, against the growth of the Gram-negative Escherichia coli and Gram-positive Staphylococcus aureus bacteria. X-ray diffraction, Fourier transform infrared spectroscopy and Raman spectroscopy were confirmed the successful synthesize of metal organic framework and incorporation of Co-MOF in to GO sheets. Scanning electron microscopy was showed the cornflower structure of GO/Co-MOF, and transmission electron microscopy was confirmed, the Co-MOF are decorated on GO. Cytotoxicity study of GO/Co-MOF using 3-[4,5-dimethylthiazol-2yl]-2,5-diphenyltetrazolium bromide (MTT) cell viability assay showed the biocompatibility to human fibroblasts cell over 72 h. The growth inhibition of the Escherichia coli and Staphylococcus aureus bacteria are reached over 99% for bacteria concentration of 100 µg/mL. The excellent antibacterial activity of GO based Co-MOF is linked to synergistic effect of sharp edges of the GO sheets and the toxic effect of cobalt ions (Co2+) which are released from their surfaces. The GO/Co-MOF radical scavenging assay was measured using 1,1-diphenyl-2-picrylhydrazyl (DPPH) antioxidant assay for samples incubated with cells which confirmed the minimum radicals' toxicity on bacteria. This novel graphene oxide based MOF with its intrinsic superior porous structure, highly active metal coordination, and commercial linker, is an excellent promising candidate to use in biological and pharmaceutical applications as high potential sustained bactericidal materials.

Magnetoelectric nanocomposite scaffold for high yield differentiation of mesenchymal stem cells to neural-like cells.

While the differentiation factors have been widely used to differentiate mesenchymal stem cells (MSCs) into various cell types, they can cause harm at the same time. Therefore, it is beneficial to propose methods to differentiate MSCs without factors. Herein, magnetoelectric (ME) nanofibers were synthesized as the scaffold for the growth of MSCs and their differentiation into neural cells without factors. This nanocomposite takes the advantage of the synergies of the magnetostrictive filler, CoFe2 O 4 nanoparticles (CFO), and piezoelectric polymer, polyvinylidene difluoride (PVDF). Graphene oxide nanosheets were decorated with CFO nanoparticles for a proper dispersion in the polymer through a hydrothermal process. After that, the piezoelectric PVDF polymer, which contained the magnetic nanoparticles, underwent the electrospun process to form ME nanofibers, the ME property of which has the potential to be used in areas such as tissue engineering, biosensors, and actuators.

Functionalized reduced graphene oxide as a lateral flow immuneassay label for one-step detection of Escherichia coli O157:H7.

In this study, graphene oxide (GO) and reduced graphene oxide (rGO) were used as visual labels in a lateral flow assay for detection of E. coli O157:H7. The color intensity was employed for the quantitative measurements of the target bacteria. Quantitative results showed that in comparison to GO, rGO can provide higher color intensity owing to enhanced light absorption following chemical reduction. Our results confirm that the visual limit of detection of the target bacteria by rGO is ∼105 colony forming unit per milliliter (CFU/ml), which closely compares with current alternative techniques using gold nanoparticles. The performance and practicability of the rGO-based test strips for detection of the target bacteria in milk and drinking water were validated with conventional plating and colony counting techniques. Results suggest that the proposed lateral flow assay is sensitive, specific, and affordable. It has also the potential to become a widely used detection technique for E. coli O157:H7 and a wide variety of other analytes.

Hydrogen sensing properties of nanocomposite graphene oxide/Co-based metal organic frameworks (Co-MOFs@GO).

This paper reports on hydrogen sensing based graphene oxide hybrid with Co-based metal organic frameworks (Co-MOFs@GO) prepared by the hydrothermal process. The texture and morphology of the hybrid were characterized by powder x-ray diffraction, scanning electron microscopy and Brunauer-Emmett-Teller analysis. Porous flower like structures assembled from Co-MOFs and GO flakes with sufficient specific surface area are obtained, which are ideal for gas molecules diffusion and interactions. Sensing performance of Co-MOFs@GO were tested and also improved by sputtering platinum (Pt) as a catalyst. The Pt-sputtered Co-MOFs@GO show outstanding hydrogen resistive-sensing with response and recovery times below 12 s at 15 °C. Also, they show stable, repeatable and selective responses to the target gas which make it suitable for the development of a high performance hydrogen sensor.

Simultaneous Gene Delivery and Tracking through Preparation of Photo-Luminescent Nanoparticles Based on Graphene Quantum Dots and Chimeric Peptides.

Designing suitable nano-carriers for simultaneous gene delivery and tracking is in the research priorities of the molecular medicine. Non-toxic graphene quantum dots (GQDs) with two different (green and red) emission colors are synthesized by Hummer's method and characterized by UV-Vis, Photoluminescence (PL), Fourier Transform Infrared (FTIR) and Raman spectroscopies, Atomic Force Microscopy (AFM), Scanning Electron Microscopy (SEM) and Transmission Electron Microscopy (TEM). The GQDs are conjugated with MPG-2H1 chimeric peptide and plasmid DNA (pDNA) by non-covalent interactions. Following conjugation, the average diameter of the prepared GQDs increased from 80 nm to 280 nm in complex structure, and the ζ-potential of the complex increased (from -36.87 to -2.56 mV). High transfection efficiency of the nano-carrier and results of confocal microscopy demonstrated that our construct can be considered as a nontoxic carrier with dual functions for gene delivery and nuclear targeting.

Graphene/cobalt nanocarrier for hyperthermia therapy and MRI diagnosis.

Graphene/cobalt nanocomposites are promising materials for theranostic nanomedicine applications, which are defined as the ability to diagnose, provide targeted therapy and monitor the response to the therapy. In this study, the composites were synthesized via chemical method, using graphene oxide as the source material and assembling cobalt nanoparticles of 15nm over the surface of graphene sheets. Various characterization techniques were then employed to reveal the morphology, size and structure of the nanocomposites, such as X-ray diffraction analysis, X-ray photoelectron spectroscopy, Fourier transform infrared spectroscopy, high resolution transmission electron microscopy and ultraviolet visible spectroscopy. Using ion-coupled plasma optical emission spectroscopy, cobalt concentration in the nanocomposites was found to be 80%. In addition, cytotoxicity of graphene/cobalt nanocomposites were evaluated using 3-[4,5-dimethylthiazol-2yl]-2,5-diphenyltetrazolium bromide or MTT assay. MTT viability assay exhibited biocompatibility to L929 mouse fibroblasts cells, under a high dose of 100µg/mL over 24h. Hyperthermia results showed the superior conversion of electromagnetic energy into heat at 350kHz frequency for 0.01 and 0.005g/L of the nanocomposites solution. The measured heat generation and energy transfer results were anticipated by the finite element analysis, conducted for the 3D structure. Magnetic resonance imaging characteristics also showed that negatively charge graphene/cobalt nanocomposites are suitable for T1-weighted imaging.

The different fate of satellite cells on conductive composite electrospun nanofibers with graphene and graphene oxide nanosheets.

Electrospinning of composite polymer solutions provides fantastic potential to prepare novel nanofibers for use in a variety of applications. The addition of graphene (G) and graphene oxide (GO) nanosheets to bioactive polymers was found to enhance their conductivity and biocompatibility. Composite conductive nanofibers of polyaniline (PANI) and polyacrylonitrile (PAN) with G and GO nanosheets were prepared by an electrospinning process. The fabricated membranes were investigated by physical and chemical examinations including scanning electron microscopy (SEM), Raman spectroscopy, x-ray diffraction (XRD) and tensile assay. The muscle satellite cells enriched by a pre-plating technique were cultured in the following and their proliferation and differentiation behavior studied by MTT, Real-Time PCR assays and 4', 6-diamidino-2-phenylindole (DAPI) staining. The cultured cells on composite nanofibrous PAN/PANI-CSA/G confirmed a higher proliferation and differentiation value compared to other groups including PAN/PANI-CSA/GO and PAN/PANI-CSA scaffolds. Furthermore, the higher stiffness of the former scaffold showed a lower cell spreading as a function of stem cell activation into more proliferative cells. It is supposed that the enhanced conductivity value in addition to relative higher stiffness of the PAN/PANI-CSA/G composite nanofibers plays a favorable role for proliferation and differentiation of satellite cells.

Curcumin-reduced graphene oxide sheets and their effects on human breast cancer cells.

Curcumin (as a natural reductant material) was utilized for green reduction and functionalization of chemically exfoliated graphene oxide (GO) sheets. The π-π attachment of the curcumin molecules onto the curcumin-reduced graphene oxide (rGO) sheets was confirmed by Raman and Fourier transform infrared spectroscopies. Zeta potential of the GO sheets decreased from about -40 mV to -20 mV, after the green reduction and functionalization. The probable cytotoxicity of the curcumin-rGO sheets was studied through their interactions with two human breast cancer cell lines (MDA-MB-231 and SKBR3 cell lines) and a normal cell line (mouse fibroblast L929 cell line). The curcumin-rGO sheet with concentrations <70 µg/mL in the cell culture medium, not only exhibited no significant toxicity and/or cell morphological changes, but also caused some cell growths (~25% after 48 h incubation time). Nevertheless, at 70 µg/mL, initiation of some cell morphological changes was observed. At higher concentrations (e.g., 100 µg/mL), some slight cytotoxic effects (resulting in ~15-25% cell destruction) were detected by MTT assay. In addition, the interaction of the rGO sheets and cells resulted in apoptosis as well as morphological transformation of the cells (from elongated to roundup morphology). These results indicated the concentration-dependent toxicity of functionalized-rGO nanomaterials (here, curcumin-rGO) at the threshold concentration of ~100 µg/mL.