A potent formula against triple-negative breast cancer-sorafenib-carbon nanotubes-folic acid: Targeting, apoptosis triggering, and bioavailability enhancing.

Triple-negative breast cancer (TNBC) has short survival rates. This study aimed to prepare a novel formula of sorafenib, carbon nanotubes (CNTs), and folic acid to be tested as a drug delivery system targeting versus TNBC compared with free sorafenib and to evaluate the formula stability, in vitro pharmacodynamic, and in vivo pharmacokinetic properties. The formula preparation was done by the synthesis of polyethylene glycol bis amine linker, CNT PEGylation, folic acid attachment, and sorafenib loading. The prepared formula has been characterized using X-ray diffraction, Flourier-transform infrared, 1HNMR, UV, high resolution-transmission electron microscope, field emission scanning electron microscopy, and Zeta potential. In vitro studies included drug release determination, MTT assay, flow cytometry to determine the apoptotic stage with percent, cell cycle analysis, and apoptotic marker assays for caspase-3, 8, 9, cytochrome c, and BCL-2. The in vivo study was performed to determine bioavailability and half-life in rats. The in vitro MTT antiproliferative assay revealed that the formula was threefold more cytotoxic toward TNBC cells than free sorafenib, and the flow cytometry showed a significant increase in apoptosis and necrosis. The formula has a greater inhibitory effect on BCL-2 and a lessening effect on cytochrome c and caspases 3, 8, and 9 than free sorafenib. In vivo experiments proved that our novel formula was superior to free sorafenib by increasing bioavailability by eight times and prolonging the half-life by three times. These results confirmed the successful preparation of the desired formula with better pharmacodynamic and pharmacokinetic properties. These promising results may show a novel therapeutic strategy for TNBC patients.

Silver decorated nickel oxide nanoflake/carbon nanotube nanocomposite as an efficient electrocatalyst for ethanol oxidation.

The higher energy density and lesser toxicity of ethanol compared to methanol make it an ideal combustible renewable energy source in fuel cells. Finding suitable cost-effective electrocatalysts that can oxidize ethanol in ethanol-based fuel cells is a major challenge. With their high catalytic activity and stability in alkaline media, transition metal-based catalysts are ideal candidates for alkaline direct ethanol fuel cells. Nickel-based nanomaterials and composites exhibit high electrocatalytic activity, which makes them predominant candidates for the electrochemical oxidation of ethanol. In this study, the electrocatalytic activity of a nickel oxide flower-like structure was explored. Forming a nanocomposite of NiO in combination with carbon nanotubes (CNTs), NiO/CNTs, as a substrate led to an increase in the stability of the electrocatalyst in alkaline media. Furthermore, the electrocatalytic activity of the NiO/CNT nanocomposite was greatly enhanced by decorating the surface with different ratios of silver (Ag). Ag/NiO/CNT composites with different Ag ratios, namely, 25% and 50% by weight, were studied. The Ag 25%/NiO/CNT weight ratio showed a maximum ethanol conversion. At an ethanol concentration of 300 mM, the electrochemical oxidation current density was found to be 57.1 ± 0.2 mA cm-2 for the 25% by weight Ag ratio, with a five-fold increase in the current density (compared to NiO/CNTs (10 ± 0.34 mA cm-2)). Furthermore, the nanocomposite synthesized here (Ag 25%/NiO/CNTs) showed a significantly higher energy conversion (current per ethanol concentration) rate compared to other reported NiO-based catalysts. These results open real opportunities for designing high efficiency ethanol fuel cell catalysts.

Nickel and cobalt-based tungstate nanocomposites as promising electrocatalysts in alkaline direct methanol fuel cells.

In this work, a non-precious group metal (non-PGM) electrocatalyst based on transition metals is introduced as a promising solution for enhancing the efficiency of direct methanol fuel cell (DMFC). Nickel-cobalt mixed tungstate was prepared using a simple co-precipitation method with different molar ratios of Ni, Co and W. The prepared materials were tested and validated using different characterization techniques. It was observed using SEM that the materials are agglomerated amorphous random circular nanocomposite structures. The electrochemical performance of the prepared electrocatalysts revealed that the best nanocomposite was the one with the Ni : Co : W ratio of 1 : 1 : 1.5 (W1.5). This composite showed a higher current density of 229 mA cm-2 towards methanol oxidation at a scan rate of 50 mV s-1 in 1 M methanol at 0.6 V, with the lowest onset potential of 0.33 V. The obtained results present a new strong non-PGM material for direct methanol electro-oxidation reactions and open new doors for economic and earth-abundant electrocatalysts as an alternative to expensive commercially available catalysts.

Impedimetric Detection of Cancer Markers Based on Nanofiber Copolymers.

The sensitive determination of folate receptors (FRs) in the early stages of cancer is of great significance for controlling the progression of cancerous cells. Many folic acid (FA)-based electrochemical biosensors have been utilized to detect FRs with promising performances, but most were complicated, non-reproducible, non-biocompatible, and time and cost consuming. Here, we developed an environmentally friendly and sensitive biosensor for FR detection. We proposed an electrochemical impedimetric biosensor formed by nanofibers (NFs) of bio-copolymers prepared by electrospinning. The biosensor combines the advantages of bio-friendly polymers, such as sodium alginate (SA) and polyethylene oxide (PEO) as an antifouling polymer, with FA as a biorecognition element. The NF nanocomposites were characterized using various techniques, including SEM, FTIR, zeta potential (ZP), cyclic voltammetry (CV), and electrochemical impedance spectroscopy (EIS). We evaluated the performance of the NF biosensor using EIS and demonstrated FR detection in plasma with a limit of detection of 3 pM. Furthermore, the biosensor showed high selectivity, reliability, and good stability when stored for two months. This biosensor was constructed from 'green credentials' holding polymers that are highly needed in the new paradigm shift in the medical industry.

Core-Shell Nanostructured Drug Delivery Platform Based on Biocompatible Metal-Organic Framework-Ligated Polyethyleneimine for Targeted Hepatocellular Carcinoma Therapy.

Multifunctional nanosized metal-organic frameworks (NMOFs) have advanced rapidly over the past decade to develop drug delivery systems (DDSs). These material systems still lack precise and selective cellular targeting, as well as the fast release of the quantity of drugs that are simply adsorbed within and on the external surface of nanocarriers, which hinders their application in the drug delivery. Herein, we designed a biocompatible Zr-based NMOF with an engineered core and the hepatic tumor-targeting ligand, glycyrrhetinic acid grafted to polyethyleneimine (PEI) as the shell. The improved core-shell serves as a superior nanoplatform for efficient controlled and active delivery of the anticancer drug doxorubicin (DOX) against hepatic cancer cells (HepG2 cells). In addition to their high loading capacity of 23%, the developed nanostructure DOX@NMOF-PEI-GA showed an acidic pH-stimulated response and extended the drug release time to 9 days as well as enhanced the selectivity toward the tumor cells. Interestingly, the DOX-free nanostructures showed a minimal toxic effect on both normal human skin fibroblast (HSF) and hepatic cancer cell line (HepG2), but the DOX-loaded nanostructures exhibited a superior killing effect toward the hepatic tumor, thus opening the way for the active drug delivery and achieving efficient cancer therapy applications.

Dual-ligated metal organic framework as novel multifunctional nanovehicle for targeted drug delivery for hepatic cancer treatment.

In the last decade, nanosized metal organic frameworks (NMOFs) have gained an increasing applicability as multifunctional nanocarriers for drug delivery in cancer therapy. However, only a limited number of platforms have been reported that can serve as an effective targeted drug delivery system (DDSs). Herein, we report rational design and construction of doxorubicin (DOX)-loaded nanoscale Zr (IV)-based NMOF (NH2-UiO-66) decorated with active tumor targeting moieties; folic acid (FA), lactobionic acid (LA), glycyrrhetinic acid (GA), and dual ligands of LA and GA, as efficient multifunctional DDSs for hepatocellular carcinoma (HCC) therapy. The success of modification was exhaustively validated by various structural, thermal and microscopic techniques. Biocompatibility studies indicated the safety of pristine NH2-UiO-66 against HSF cells whereas DOX-loaded dual-ligated NMOF was found to possess superior cytotoxicity against HepG2 cells which was further confirmed by flow cytometry. Moreover, fluorescence microscopy was used for monitoring cellular uptake in comparison to the non-ligated and mono-ligated NMOF. Additionally, the newly developed dual-ligated NMOF depicted a pH-responsiveness towards the DOX release. These findings open new avenues in designing various NMOF-based DDSs that actively target hepatic cancer to achieve precise therapy.

Chitosan and EDTA conjugated graphene oxide antinematodes in Eggplant: Toward improving plant immune response.

A new strategy regarding the fabrication of chitosan (CS) or ethylene diamine tetraacetic acid (EDTA) on graphene oxide (GO) was performed. The nematocidal potential against Meloidogyne incognita causing root-knot infection in eggplant was tested. The plant immune response was investigated through measuring the photosynthetic pigments, phenols and proline contents, oxidative stress, and antioxidant enzymes activity. Results indicating that, the treatment by pure GO recorded the most mortality percentages of M. incognita 2nd juveniles followed by GO-CS then GO-EDTA. In vivo greenhouse experiments reveals that, the most potent treatment in reducing nematodes was GO-CS which recorded 85.42%, 75.3%, 55.5%, 87.81%, and 81.32% in numbers of 2nd juveniles, galls, females, egg masses and the developmental stage, respectively. The highest chlorophyll a (104%), chlorophyll b (46%), total phenols (137.5%), and free proline (145.2%) were recorded in GO-CS. The highest malondialdehyde (MDA) value was achieved by GO-EDTA (7.22%), and hydrogen peroxide (H2O2) content by 47.51% after the treatment with pure GO. Treatment with GO-CS increased the activities of catalase (CAT) by 98.3%, peroxidase (POD) by 97.52%, polyphenol oxidase (PPO) by 113.8%, and superoxide dismutase (SOD) by 42.43%. The synthesized nanocomposites increases not only the nematocidal activity but also the plant systematic immune response.

Graphene oxide and its nanocomposites with EDTA or chitosan induce apoptosis in MCF-7 human breast cancer.

To achieve the advanced anticancer activity of nanocomposites fabricated with graphene oxide (GO), a novel procedure was used during the fabrication of chitosan (CS) or ethylene diamine tetra acetic acid (EDTA). The synthesized GO-based nanocomposites were distinguished through different analytical techniques. The cytotoxic activity was examined using MTT assays against three different cancer cell lines. Cell cycle distribution and apoptosis were studied by flow cytometry. Caspase-8, caspase-9, and VEGFR-2 levels were determined using the ELISA technique. HRTEM results revealed a regular 2D thin sheet with a transparent surface in non-modified GO and for GO-CS, the surface of GO has clear cuts and lines had developed due to CS insertion. Concerning the MCF-7 breast cancer cell line, the lowest IC50 values were recorded, suggesting the most powerful cytotoxic effect on breast cancer cells. Treatment with GO-EDTA resulted in the lowest IC50 value of 3.8 ± 0.18 µg mL-1. As indicated by the annexin V-FITC apoptosis assay, the total apoptosis highest percentage was in GO-EDTA treatment (30.12%). In addition, the study of cell cycle analysis showed that GO-EDTA arrested the cell cycle primarily in the G0/G1 phase (33.74%). CS- and EDTA-conjugated GO showed an anti-cancer activity through their cytotoxic effect against the MCF-7 breast cancer cell line.

Oxidation of polyphenols and inhibition of photosystem II under acute photooxidative stress.

MAIN CONCLUSION: We observed a close correlation between the inhibition of photosystem II and the oxidation of polyphenols during an acute oxidative stress in sunflower leaf discs. To assess the physiological significance of polyphenols as antioxidants in planta, we compared the kinetics of polyphenols oxidation with the inhibition of the photosynthetic apparatus in sunflower leaf discs exposed to an acute photooxidative stress. Illumination of leaf discs in the presence of methyl viologen induced a rapid and large non-photochemical quenching of chlorophyll-a fluorescence, which was reversed after 4 h of treatment as indicated by the ≈ 30% increases of the steady-state (Fs) and maximal (Fm') levels of chlorophyll-a fluorescence relative to the first hour of treatment. This event coincided with the accelerated decreases of the maximum (Fv/Fm) and effective (∆F/Fm') quantum yields of photosystem II, and also with the beginning of polyphenols oxidation, estimated by the UV absorbance of methanolic leaf extracts, and supported by the Folin-Ciocalteu method and cyclic voltammetry. The decreases of Fv/Fm and the concentrations of reducing polyphenols were highly correlated (R2 = 0.877) during the experiment. Coherent with the decrease of UV absorbance of methanolic extracts, polyphenol oxidation resulted in a marked decrease of UV absorbance of leaf epidermis. Also, polymerization of oxidized polyphenols caused the accumulation of brown pigments in the MV-treated leaf discs, decreasing leaf reflectance, especially at 550 and 740 nm. Fluorescence intensities were also decreased during the MV treatment. Interestingly, the emission fluorescence ratio F740/F684 (excitation at 550 nm) decreased similarly to Fv/Fm (R2 = 0.981) due to the brown pigments. Moreover, the excitation fluorescence ratio F484/F680 (emission at 740 nm) was linearly correlated (R2 = 0.957) to ∆F/Fm', indicating a decrease of efficiency of energy transfer between the antenna pigments to the photosystem II reaction center during the oxidative stress. These results support the view that polyphenols can be effective antioxidants protecting the plants against reactive oxygen species.