Efficacy of copper nanoparticles encapsulated in soya lecithin liposomes in treating breast cancer cells (MCF-7) in vitro.

Cancer is one of the leading causes of death, which has attracted the attention of the scientific world to the search for efficient methods for treatment. With the great development and regeneration of nanotechnology over the last 25 years, various nanoparticles in different structures, shapes and composites provide good potential for cancer therapy. There are several drugs approved by FDA used in breast cancer treatment like Cyclophosphamide, Doxorubicin Hydrochloride, Femara, Herceptin, etc. Each has several side effects as well as treatment, which limits the use of drugs due to heart failure, pulmonary dysfunction, or immunodeficiency. Recently, such side effects are greatly reduced by using innovative delivery techniques. Some drugs have been approved for use in cancer treatment under the concept of drug delivery, such as Doxil (liposomal loaded doxorubicin). The purpose of this study is to investigate the effect of copper nanoparticles (CuNPs) as a drug model for cancer treatment, either in their free form or encapsulated in Soy lecithin liposomes (SLP) from plant origin as a cheap source of lipids. CuNPs were prepared by the chemical reduction method and loaded onto SLP through the thin film hydration method. The drug model Cu/SLP was successfully combined. The characteristics of the free CuNPs, liposomes, and the combined form, zeta potential, size distribution, drug encapsulation efficiency (EE%), drug release profile, Fourier transform infrared (FTIR), and transmission electron microscopy (TEM), were checked, followed by an in vitro study on the breast cancer cell line Mcf-7 as a model for cytotoxicity evaluation. The optimal Cu/SLP had a particle mean size of 81.59 ± 14.93 nm, a negative zeta potential of - 50.7 ± 4.34 mV, loaded CuNPs showed an EE% of 78.9%, a drug release profile for about 50% of the drug was released after 6 h, and FTIR analysis was recorded. The cytotoxicity assay showed that the IC50 of Cu/SLP is smaller than that of free CuNPs. These results give clear evidence of the efficacy of using the combined Cu/SLP rather than CuNPs alone as a model drug carrier prepared from plant origin against cancer, both medically and economically.

Innovative technologies to enhance oil recovery.

The processes for extracting and refining edible oils are well-established in industry at different scales. However, these processing lines encounter inefficiencies and oil losses when recovering crude or refined oil. Palm oil and olive oil extraction methods are used mainly as a combination of physical, thermal, and centrifugal methods to recover crude oil, which results in oil losses in the olive pomace or in palm oil effluents. Seed oils generally require a seed steam conditioning, and cooking stage, followed by physical oil recovery through an inefficient expeller. Most of the crude oil remaining in the expeller cake is then recovered by hexane. Crude seed oil is further refined in stages that also undergo oil losses. This chapter provides an overview of innovative technologies using microwave, ultrasound, megasonic and pulsed electric field energies, which can be used in the above-mentioned crude and refined oil processes to improve oil recovery. This chapter describes traditional palm oil, olive oil, and seed oil processes, as well as the specific process interventions that have been tested with these technologies. The impact of such technology interventions on oil quality is also summarized.

Dopamine / Artesunate loaded polyhydroxybutyrate-g-cellulose- magnetite zinc oxide core shell nanocomposites: Synergistic antimicrobial and anticancer efficacy.

In this study, polyhydroxybutyrate-g-cellulose - Fe3O4/ZnO (PHB-g-cell- Fe3O4/ZnO) nanocomposites (NCs) was synthesized and used as a delivery system for Dopamine (DO) /Artesunate (ART) drugs. Different types of cells (Ccell, Scell, Pcell) grafted with PHB were designed and mixed with different contents of Fe3O4/ZnO. Physical and chemical features of PHB-g-cell-Fe3O4/ZnO NCs were detected by FTIR, XRD, dynamic light scattering, transmission electron microscopy, and scanning electron microscopy. ART/DO drugs were loaded into PHB-g-cell- Fe3O4/ZnO NCs by single emulsion technique. The rate of drugs release was studied at different pHs (5.4, 7.4). Owing to the overlap between the absorption bands of both drugs, differential pulse adsorptive cathodic stripping voltammetry (DP-AdCSV) was used for the estimation of ART. To study the mechanism of ART and DO release, zero-order, first order, Hixon Crowell, Higuchi and Korsmeyer-Peppas models were applied to the experiment results. The results showed that Ic50 of ART @PHB-g-Ccell-10% DO@ Fe3O4/ZnO, ART @PHB-g-Pcell-10% DO@ Fe3O4/ZnO and ART @PHB-g-Scell-10% DO@ Fe3O4/ZnO were 21.22, 12.3, and 18.11 µg/mL, respectively. The results revealed that ART @PHB-g-Pcell-10% DO@ Fe3O4/ZnO was more effective against HCT-116 than the carriers loaded by a single drug. The antimicrobial efficacy of the nano-loaded drugs was considerably improved compared with free drugs.

Reversion of breast epithelial polarity alterations caused by obesity.

Molecular links between breast cancer risk factors and pro-oncogenic tissue alterations are poorly understood. The goal of this study was to characterize the impact of overweight and obesity on tissue markers of risk, using normal breast biopsies, a mouse model of diet-induced obesity, and cultured breast acini. Proliferation and alteration of epithelial polarity, both necessary for tumor initiation, were quantified by immunostaining. High BMI (>30) and elevated leptin were associated with compromised epithelial polarity whereas overweight was associated with a modest increase in proliferation in human and mice mammary glands. Human serum with unfavorable adipokine levels altered epithelial polarization of cultured acini, recapitulating the effect of leptin. Weight loss in mice led to metabolic improvements and restored epithelial polarity. In acini cultures, alteration of epithelial polarity was prevented by antioxidants and could be reverted by normalizing culture conditions. This study shows that obesity and/or dietary factors modulate tissue markers of risk. It provides a framework to set target values for metabolic improvements and to assess the efficacy of interventional studies aimed at reducing breast cancer risk.

Thymoquinone, piperine, and sorafenib combinations attenuate liver and breast cancers progression: epigenetic and molecular docking approaches.

BACKGROUND: Traditional herbal medicine has been used for centuries to cure many pathological disorders, including cancer. Thymoquinone (TQ) and piperine (PIP) are major bioactive constituents of the black seed (Nigella sativa) and black pepper (Piper nigrum), respectively. The current study aimed to explore the potential chemo-modulatory effects, mechanisms of action, molecular targets, and binding interactions after TQ and PIP treatments and their combination with sorafenib (SOR) against human triple-negative breast cancer (MDA-MB-231) and liver cancer (HepG2) cells. METHODS: We determined drug cytotoxicity by MTT assay, cell cycle, and death mechanism by flow cytometry. Besides, the potential effect of TQ, PIP, and SOR treatment on genome methylation and acetylation by determination of DNA methyltransferase (DNMT3B), histone deacetylase (HDAC3) and miRNA-29c expression levels. Finally, a molecular docking study was performed to propose potential mechanisms of action and binding affinity of TQ, PIP, and SOR with DNMT3B and HDAC3. RESULTS: Collectively, our data show that combinations of TQ and/or PIP with SOR have significantly enhanced the SOR anti-proliferative and cytotoxic effects depending on the dose and cell line by enhancing G2/M phase arrest, inducing apoptosis, downregulation of DNMT3B and HDAC3 expression and upregulation of the tumor suppressor, miRNA-29c. Finally, the molecular docking study has identified strong interactions between SOR, PIP, and TQ with DNMT3B and HDAC3, inhibiting their normal oncogenic activities and leading to growth arrest and cell death. CONCLUSION: This study reported TQ and PIP as enhancers of the antiproliferative and cytotoxic effects of SOR and addressed the mechanisms, and identified molecular targets involved in their action.

Benzimidazole Derivatives Suppress Fusarium Wilt Disease via Interaction with ERG6 of Fusarium equiseti and Activation of the Antioxidant Defense System of Pepper Plants.

Sweet pepper (Capsicum annuum L.), also known as bell pepper, is one of the most widely grown vegetable crops worldwide. It is attacked by numerous phytopathogenic fungi, such as Fusarium equiseti, the causal agent of Fusarium wilt disease. In the current study, we proposed two benzimidazole derivatives, including 2-(2-hydroxyphenyl)-1-H benzimidazole (HPBI) and its aluminum complex (Al-HPBI complex), as potential control alternatives to F. equiseti. Our findings showed that both compounds demonstrated dose-dependent antifungal activity against F. equiseti in vitro and significantly suppressed disease development in pepper plants under greenhouse conditions. According to in silico analysis, the F. equiseti genome possesses a predicted Sterol 24-C-methyltransferase (FeEGR6) protein that shares a high degree of homology with EGR6 from F. oxysporum (FoEGR6). It is worth mentioning that molecular docking analysis confirmed that both compounds can interact with FeEGR6 from F. equiseti as well as FoEGR6 from F. oxysporum. Moreover, root application of HPBI and its aluminum complex significantly enhanced the enzymatic activities of guaiacol-dependent peroxidases (POX), polyphenol oxidase (PPO), and upregulated four antioxidant-related enzymes, including superoxide dismutase [Cu-Zn] (CaSOD-Cu), L-ascorbate peroxidase 1, cytosolic (CaAPX), glutathione reductase, chloroplastic (CaGR), and monodehydroascorbate reductase (CaMDHAR). Additionally, both benzimidazole derivatives induced the accumulation of total soluble phenolics and total soluble flavonoids. Collectively, these findings suggest that the application of HPBI and Al-HPBI complex induce both enzymatic and nonenzymatic antioxidant defense machinery.

Composite nanofiber formation using a mixture of cellulose acetate and activated carbon for oil spill treatment.

Oil and organic pollutants are significant disasters affecting the aquatic ecosystem and human health. A novel nanofiber composite from cellulose acetate/activated carbon (CA/AC) was successfully fabricated by the electrospinning technique. CA/AC nanofiber composites were prepared from 10% (w/v) polymer solutions dissolving in DMA/acetone ratio 1:3 (v/v) with adding three different percentages of AC (3.7, 5.5, and 6.7%) to the total weight of CA. The prepared CA/AC nanofiber composite morphology reveals randomly oriented bead-free fibers with submicron fiber diameter. CA/AC nanofiber composites were further characterized by TGA, DSC, and surface area analysis. Water uptake was investigated for fabricated fibers at different pH. Oil adsorption was conducted in both static (oil only) and dynamic (oil/water) systems to estimate the adsorption capacity of prepared composites to treat heavy and light machine oils. The results showed increased oil adsorption capacity incorporating activated carbon into CA nanofiber mats. The maximum sorption capacity reached 8.3 and 5.5 g/g for heavy and light machine oils obtained by CA/AC5.5 (AC, 5.5%). A higher oil uptake was reported for the CA/AC composite nanofibers and showed a constant sorption capacity after the second recycles in the reusability test. Of isotherm models, the most applicable model was the Freundlich isotherm model. The result of kinetic models proved the fit of the pseudo-second-order kinetic model to the adsorption system.

XDecompo: Explainable Decomposition Approach in Convolutional Neural Networks for Tumour Image Classification.

Of the various tumour types, colorectal cancer and brain tumours are still considered among the most serious and deadly diseases in the world. Therefore, many researchers are interested in improving the accuracy and reliability of diagnostic medical machine learning models. In computer-aided diagnosis, self-supervised learning has been proven to be an effective solution when dealing with datasets with insufficient data annotations. However, medical image datasets often suffer from data irregularities, making the recognition task even more challenging. The class decomposition approach has provided a robust solution to such a challenging problem by simplifying the learning of class boundaries of a dataset. In this paper, we propose a robust self-supervised model, called XDecompo, to improve the transferability of features from the pretext task to the downstream task. XDecompo has been designed based on an affinity propagation-based class decomposition to effectively encourage learning of the class boundaries in the downstream task. XDecompo has an explainable component to highlight important pixels that contribute to classification and explain the effect of class decomposition on improving the speciality of extracted features. We also explore the generalisability of XDecompo in handling different medical datasets, such as histopathology for colorectal cancer and brain tumour images. The quantitative results demonstrate the robustness of XDecompo with high accuracy of 96.16% and 94.30% for CRC and brain tumour images, respectively. XDecompo has demonstrated its generalization capability and achieved high classification accuracy (both quantitatively and qualitatively) in different medical image datasets, compared with other models. Moreover, a post hoc explainable method has been used to validate the feature transferability, demonstrating highly accurate feature representations.

Metal Complexation of Bis-Chalcone Derivatives Enhances Their Efficacy against Fusarium Wilt Disease, Caused by Fusarium equiseti, via Induction of Antioxidant Defense Machinery.

Sweet pepper (Capsicum annuum L.) is one of the most widely produced vegetable plants in the world. Fusarium wilt of pepper is one of the most dangerous soil-borne fungal diseases worldwide. Herein, we investigated the antifungal activities and the potential application of two chalcone derivatives against the phytopathogenic fungus, Fusarium equiseti, the causal agent of Fusarium wilt disease in vitro and in vivo. The tested compounds included 3-(4-dimethyl amino-phenyl)-1-{6-[3-(4 dimethyl amino-phenyl)-a cryloyl]-pyridin-2-yl}-propanone (DMAPAPP) and its metal complex with ruthenium III (Ru-DMAPAPP). Both compounds had potent fungistatic activity against F. equiseti and considerably decreased disease progression. The tested compounds enhanced the vegetative growth of pepper plants, indicating there was no phytotoxicity on pepper plants in greenhouse conditions. DMAPAPP and Ru-DMAPAPP also activated antioxidant defense mechanisms that are enzymatic, including peroxidase, polyphenole oxidase, and catalase, and non-enzymatic, such as total soluble phenolics and total soluble flavonoids. DMAPAPP and Ru-DMAPAPP also promoted the overexpression of CaCu-SOD and CaAPX genes. However, CaGR and CaMDHAR were downregulated. These results demonstrate how DMAPAPP and Ru-DMAPAPP could be employed as a long-term alternative control approach for Fusarium wilt disease as well as the physiological and biochemical mechanisms that protect plants.

Synthesis and validation of ultrasensitive stripping voltammetric sensor based on polypyrrole@ZnO/Fe3O4 core-shell nanostructure for picomolar detection of artesunate and dopamine drugs.

A stripping voltammetric sensor for ultrasensitive detection of artesunate (ART) and dopamine HCl (DA) has been successfully developed using a Ppy@ZnO/Fe3O4 core-shell nanocomposite ([PZM])-modified carbon paste sensor (MCPS). Fourier transform infrared spectroscopy, X-ray diffraction, field emission scanning electron microscopy, energy-dispersive X-ray spectroscopy, dynamic light scattering, Brunauer-Emmett-Teller surface area method, and high-resolution transmission electron microscopy were used to characterize the physicochemical properties of the nanomaterials. Noteworthily, the morphology of [PZM] reveals a spherical core-shell nanostructure with an increase in the average diameter range of 20-37.5 nm (specific surface area (SSA) of 28.5 m2 g-1 (0.0247 cm3 g-1)) when compared with the average diameter range 7.5-15.7 nm (SSA of 5.43 m2 g-1 (0.0111 cm3 g-1)) of ZnO/Fe3O4[ZM]. The [PZM] MCPS provided the best electroactive surface area (0.078 cm2) and the least electrocatalytic activity (Rst = 370 Ω). Furthermore, the MCPS showed low detection limits (LODs) of 0.092 pg mL-1 (0.24 pM) and 0.0046 pg mL-1 (0.03 pM) for ART and DA, respectively. Moreover, LODs were found to be 0.029 pg mL-1 (0.75 pM) and 0.014 pg mL-1 (0.09 pM) for ART mixed with 0.7 pM of DA (ART1) and DA in the presence of 2.0 pM of ART drug (DA1), respectively. In addition, the MCPS revealed a proper repeatability, reproducibility, and storage stability (93.5-90.48%). During the routine analysis, the [PZM] MCPS detected ART and DA concentrations in human urine, without interference.

MCUa: Multi-Level Context and Uncertainty Aware Dynamic Deep Ensemble for Breast Cancer Histology Image Classification.

Breast histology image classification is a crucial step in the early diagnosis of breast cancer. In breast pathological diagnosis, Convolutional Neural Networks (CNNs) have demonstrated great success using digitized histology slides. However, tissue classification is still challenging due to the high visual variability of the large-sized digitized samples and the lack of contextual information. In this paper, we propose a novel CNN, called Multi-level Context and Uncertainty aware (MCUa) dynamic deep learning ensemble model. MCUa model consists of several multi-level context-aware models to learn the spatial dependency between image patches in a layer-wise fashion. It exploits the high sensitivity to the multi-level contextual information using an uncertainty quantification component to accomplish a novel dynamic ensemble model. MCUa model has achieved a high accuracy of 98.11% on a breast cancer histology image dataset. Experimental results show the superior effectiveness of the proposed solution compared to the state-of-the-art histology classification models.

3E-Net: Entropy-Based Elastic Ensemble of Deep Convolutional Neural Networks for Grading of Invasive Breast Carcinoma Histopathological Microscopic Images.

Automated grading systems using deep convolution neural networks (DCNNs) have proven their capability and potential to distinguish between different breast cancer grades using digitized histopathological images. In digital breast pathology, it is vital to measure how confident a DCNN is in grading using a machine-confidence metric, especially with the presence of major computer vision challenging problems such as the high visual variability of the images. Such a quantitative metric can be employed not only to improve the robustness of automated systems, but also to assist medical professionals in identifying complex cases. In this paper, we propose Entropy-based Elastic Ensemble of DCNN models (3E-Net) for grading invasive breast carcinoma microscopy images which provides an initial stage of explainability (using an uncertainty-aware mechanism adopting entropy). Our proposed model has been designed in a way to (1) exclude images that are less sensitive and highly uncertain to our ensemble model and (2) dynamically grade the non-excluded images using the certain models in the ensemble architecture. We evaluated two variations of 3E-Net on an invasive breast carcinoma dataset and we achieved grading accuracy of 96.15% and 99.50%.

Diet Alters Entero-Mammary Signaling to Regulate the Breast Microbiome and Tumorigenesis.

Obesity and poor diet often go hand-in-hand, altering metabolic signaling and thereby impacting breast cancer risk and outcomes. We have recently demonstrated that dietary patterns modulate mammary microbiota populations. An important and largely open question is whether the microbiome of the gut and mammary gland mediates the dietary effects on breast cancer. To address this, we performed fecal transplants between mice on control or high-fat diets (HFD) and recorded mammary tumor outcomes in a chemical carcinogenesis model. HFD induced protumorigenic effects, which could be mimicked in animals fed a control diet by transplanting HFD-derived microbiota. Fecal transplants altered both the gut and mammary tumor microbiota populations, suggesting a link between the gut and breast microbiomes. HFD increased serum levels of bacterial lipopolysaccharide (LPS), and control diet-derived fecal transplant reduced LPS bioavailability in HFD-fed animals. In vitro models of the normal breast epithelium showed that LPS disrupts tight junctions (TJ) and compromises epithelial permeability. In mice, HFD or fecal transplant from animals on HFD reduced expression of TJ-associated genes in the gut and mammary gland. Furthermore, infecting breast cancer cells with an HFD-derived microbiome increased proliferation, implicating tumor-associated bacteria in cancer signaling. In a double-blind placebo-controlled clinical trial of patients with breast cancer administered fish oil supplements before primary tumor resection, dietary intervention modulated the microbiota in tumors and normal breast tissue. This study demonstrates a link between the gut and breast that mediates the effect of diet on cancer. SIGNIFICANCE: This study demonstrates that diet shifts the microbiome in the gut and the breast tumor microenvironment to affect tumorigenesis, and oral dietary interventions can modulate the tumor microbiota in patients with breast cancer. GRAPHICAL ABSTRACT: http://cancerres.aacrjournals.org/content/canres/81/14/3890/F1.large.jpg.

Co-delivery of norfloxacin and tenoxicam in Ag-TiO2/poly(lactic acid) nanohybrid.

A nanohybrid formulation of silver­titanium dioxide nanoparticles/poly(lactic acid) (Ag-TiO2/PLA) was designed for Norfloxacin/Tenoxicam (NOR/TENO) targeted delivery to maximize the bioavailability and minimize the side effects of the drugs. Ag-TiO2 nanoparticles were prepared via Stober method. NOR, TENO and a mixture of NOR/TENO (NT) were loaded onto Ag-TiO2 nanoparticles and coated by PLA via solution casting. The physical interaction between the drugs and carrier was confirmed by Fourier-transform infrared (FTIR) analysis. X-ray diffraction (XRD) demonstrated that Ag-TiO2 consists of a cubic phase of Ag with two phases of TiO2 (anatase and brookite). Ag nanoparticle fine spots coated with TiO2 were collected to form spheres averaging at 100 nm in size. In-vitro release behavior of drugs was studied at different pH (5.4, 7.4) and the release of drug from NT/Ag-TiO2/PLA was faster at pH 7.4. Gram-positive and Gram-negative bacteria were used to investigate antibacterial properties of the nanohybrid. Cytotoxicity of the nanohybrid using an MTT assay was studied against different tumor and normal cell lines. It was found that NT/Ag-TiO2/PLA has an excellent cytotoxic effect against various bacterial cells and tumor cell lines. In addition, antioxidant properties of the nanohybrids were tested using ABTS method and the nanohybrid showed moderate antioxidant activity.

Induction of Apoptosis by Nano-Synthesized Complexes of H2L and its Cu(II) Complex in Human Hepatocellular Carcinoma Cells.

BACKGROUND: Chemotherapy is currently the most utilized treatment for cancer. Therapeutic potential of metal complexes in cancer therapy has attracted a lot of interest. The mechanisms of action of most organometallic complexes are poorly understood. OBJECTIVE: This study was designed to explore the mechanisms governing the anti-proliferative effect of the free ligand N1,N6-bis((2-hydroxynaphthalin-1-yl)methinyl)) adipohydrazone (H2L) and its complexes of Mn(II), Co(II), Ni(II) and Cu(II). METHODS: Cells were exposed to H2L or its metal complexes where cell viability determined by MTT assay. Cell cycle was analysed by flow cytometry. In addition, qRT-PCR was used to monitor the expression of Bax and Bcl-2. Moreover, molecular docking was carried out to find the potentiality of Cu(II) complex as an inhibitor of Adenosine Deaminase (ADA). ADA, Superoxide Dismutase (SOD) and reduced Glutathione (GSH) levels were measured in the most affected cancer cell line. RESULTS: The obtained results demonstrated that H2L and its Cu(II) complex exhibited a strong cytotoxic activity compared to other complexes against HepG2 cells (IC50=4.14±0.036µM/ml and 3.2±0.02µM/ml), respectively. Both H2L and its Cu(II) complex induced G2/M phase cell cycle arrest in HepG2 cells. Additionally, they induced apoptosis in HepG2 cells via upregulation of Bax and downregulation of Bcl-2. Interestingly, the activity of ADA was decreased by 2.8 fold in HepG2 cells treated with Cu(II) complex compared to untreated cells. An increase of SOD activity and GSH level in HepG2 cells compared to control was observed. CONCLUSION: The results concluded that Cu(II) complex of H2L induced apoptosis in HepG2 cells. Further studies are needed to confirm its anti-cancer effect in vivo.

Co-Administration of Tretinoin Enhances the Anti-Cancer Efficacy of Etoposide via Tumor-Targeted Green Nano-Micelles.

Herein we report promoted anti-cancer activity via a combination strategy of synergistic chemotherapy/retinoid-based breast cancer therapy with shell-stabilized micellar green nanomedicine. Amphiphilic zein-chondroitin sulfate (ChS)-based copolymeric micelles (PMs) were successfully developed via carbodiimide coupling for concomitant delivery of etoposide (ETP) and all-trans retinoic acid (ATRA) to breast cancer. The micelles exhibited low critical micellar concentration (CMC) of 0.008 mg/mL with high encapsulation efficiencies of ETP and ATRA (61.2 and 84.29%, respectively). Calcium-mediated crosslinking of the anionic ChS micellar shell resulted in prolonged drug release with small micellar size of 222.7 nm. The micelles exhibited augmented internalization into MCF-7 breast cancer cells by virtue of ChS binding affinity to CD44 receptors overexpressed by cancer cells. Consequently, the ETP/ATRA-loaded micelles exhibited synergistic cytotoxicity against breast cancer cells as revealed by their significantly lower IC50, combination index (CI), and higherdose reduction index (DRI) in comparison to the free ETP and free ATRA or their combination. Micelles displayed superiority in reducing tumor volume, decreasing proliferation, and promoting necrosis in mice bearing Ehrlich Ascites Tumor (EAT) upon comparison to free ETP and free ATRA or their combination. Overall, the developed green zein-ChS micelles offer a promising platform for tumor-targeted delivery of hydrophobic therapeutic agents.

In-vitro evaluation of copper/copper oxide nanoparticles cytotoxicity and genotoxicity in normal and cancer lung cell lines.

BACKGROUND: Nanotoxicology is a major field of study that reveals hazard effects of nanomaterials on the living cells. METHODS: In the present study, Copper/Copper oxide nanoparticles (Cu/CuO NPs) were prepared by the chemical reduction method and characterized by different techniques such as: X-Ray Diffraction, Transmission and Scanning Electron Microscopy. Evaluation of the toxicity of Cu/CuO NPs was performed on 2 types of cells: human lung normal cell lines (WI-38) and human lung carcinoma cell (A549). To assess the toxicity of the prepared Cu/CuOs NPs, the two cell types were exposed to Cu/CuO NPs for 72 h. The half-maximal inhibitory concentration IC50 of Cu/CuO NPs for both cell types was separately determined and used to examine the cell genotoxicity concurrently with the determination of some oxidative stress parameters: nitric oxide, glutathione reduced, hydrogen peroxide, malondialdehyde and superoxide dismutase. RESULTS: Cu/CuO NPs suppressed proliferation and viability of normal and carcinoma lung cells. Treatment of both cell types with their IC50's of Cu/CuO NPs resulted in DNA damage besides the generation of reactive oxygen species and consequently the generation of a state of oxidative stress. CONCLUSION: Overall, it can be concluded that the IC50's of the prepared Cu/CuO NPs were cytotoxic and genotoxic to both normal and cancerous lung cells.

Synthesis and Design of Norfloxacin drug delivery system based on PLA/TiO2 nanocomposites: Antibacterial and antitumor activities.

Biodegradable, biocompatible and non-toxic polymer-based nanoparticles are the novel nanotherapeutic tool which is used for adsorption and encapsulation drugs. Extended release formulation of Norfloxacin antibiotic, chemotherapeutic agent model, drug in the form of encapsulated and loaded poly (lactic acid) nanocomposites-based Titanium dioxide (PLA/TiO2) was developed. Nanocomposites were prepared using different contents (1, 3, 5 wt %) and morphologies of TiO2 (spheres (S), rods (R). The dispersion of TiO2 was aided by ultrasonic technique followed by solution casting method. The morphology, particle size, crystallite size and composition of the nanocomposites were examined by SEM, TEM, XRD and FTIR. The crystallinity and thermal behavior of the nanocomposites were characterized by DSC and TGA. NOR was loaded onto TiO2 nanospheres (NOR@TiO2 (S)) and the optimum conditions for loading was investigated. Pseudo-second order model was the more adequate to represent the kinetic data. The equilibrium data followed Freundlich adsorption isotherm and the adsorption process was exothermic. NOR@TiO2 (S) was encapsulated into PLA and in vitro release behavior of drug was compared with NOR adsorbed into PLA (NOR@PLA) and nanocomposites (NOR@PLA/TiO2) using different pH (6.7, 7.4) media. To study the mechanism of NOR release, first order, Higuchi, Hixon Crowell and Korsmeyer-Peppas models were applied on the experimental results. The cytotoxicity of the loaded nanocomposites using MTT assay was studied against HepG 2, MCF-7, HCT 116, PC-3, Hela, WI-38 and WISH cells. The encapsulated (NOR@ 5S/En PLA) showed the highest cytotoxic efficacy with moderate effect on normal cells. Moreover, the nanocomposites have great potential against Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli, Salmonella and Klebsiella pneumonia. NOR@ PLA/TiO2 nanocomposites showed better antibacterial efficacy than NOR encapsulated nanocomposites. The nanocomposites could be effective vehicles for the sustained delivery of toxic anticancer drug.

Poly(3-hydroxybutyrate)/poly(amine)-coated nickel oxide nanoparticles for norfloxacin delivery: antibacterial and cytotoxicity efficiency.

Sustained release dosage forms enable prolonged and continuous release of a drug in the gastrointestinal tract for medication characterized by a short half lifetime. In this study, the effect of blending polyamine on poly(3-hydroxybutyrate) (PHB) as a carrier for norfloxacin (NF) was studied. The prepared blend was mixed with different amounts of NiO nanoparticles and characterized using FTIR analysis, X-ray diffraction analysis, thermogravimetric analysis, dynamic light scattering, transmission electron microscopy and scanning electron microscopy. It was found that the drug released from the nanocomposite has a slow rate in comparison with NiO, PHB, and PHB/polyamine blend. The highest ratio of NiO content to the matrix (highest NF loading), leads to a slower rate of drug release. The release from the nanocomposites showed a faster rate at pH = 2 than that at pH = 7.4. The mechanisms of NF adsorption and release were studied on PHB/polyamine-3% NiO nanocomposite. In addition, the antimicrobial efficacy of nanocomposites loaded with the drug was determined and compared with the free drug. Inclusion of NiO into PHB/polyamine showed a higher efficacy against Streptococcus pyogenes and Pseudomonas aeruginosa than the free NF. Moreover, the cytotoxicity of PHB/polyamine-3% NiO against HePG-2 cells was investigated and compared with PHB and PHB/polyamine loaded with the drug. The most efficient IC50 was found for NF@PHB/polyamine-3% NiO (29.67 µg mL-1). No effect on cell proliferation against the normal human cell line (WISH) was observed and IC50 was detected to be 44.95 and 70 µg mL-1 for NiO nanoparticles and the PHB/polyamine-3% NiO nanocomposite, respectively indicating a selectivity of action towards tumor cells coupled with a lack of cytotoxicity towards normal cells.

Correction to: Risk stratification of pediatric high-grade glioma: a newly proposed prognostic score.

The original version of this article unfortunately contained an error. The author apologizes for having provided an incorrect name: "Mohamed S. Zaghluol" should be "Mohamed S. Zaghloul". Given in this article is the correct author name.