Bi2O3-Doped WO3 Nanoparticles Decorated on rGO Sheets: Simple Synthesis, Characterization, Photocatalytic Performance, and Selective Cytotoxicity toward Human Cancer Cells.

Graphene derivatives and metal oxide-based nanocomposites (NCs) are being studied for their diverse applications including gas sensing, environmental remediation, and biomedicine. The aim of the present work was to evaluate the effect of rGO and Bi2O3 integration on photocatalytic and anticancer efficacy. A novel Bi2O3-WO3/rGO NCs was successfully prepared via the precipitation method. X-ray crystallography (XRD) data confirmed the crystallographic structure and the phase composition of the prepared samples. Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) analysis confirmed the loading of Bi2O3-doped WO3 NPs on rGO sheets. Energy-dispersive X-ray (EDX) results confirmed that all elements of carbon (C), oxygen (O), tungsten (W), and bismuth (Bi) were present in Bi2O3-WO3/rGO NCs. The oxidation state and presence of elemental compositions in Bi2O3-WO3/rGO NCs were verified by the X-ray photoelectron spectroscopy (XPS) study. Raman spectra indicate a reduction in carbon-oxygen functional groups and an increase in the graphitic carbon percentage of the Bi2O3-WO3/rGO NCs. The functional group present in the prepared samples was examined by Fourier transform infrared (FTIR) spectroscopy. UV analysis showed that the band gap energy of the synthesized samples was slightly decreased with Bi2O3 and rGO doping. Photoluminescence (PL) spectra showed that the recombination rate of the electron-hole pair decreased with the dopants. Degradation of RhB dye under UV light was employed to evaluate photocatalytic performance. The results showed that the Bi2O3-WO3/rGO NCs have high photocatalytic activity with a degradation rate of up to 91%. Cytotoxicity studies showed that Bi2O3 and rGO addition enhance the anticancer activity of WO3 against human lung cancer cells (A549) and colorectal cancer cells (HCT116). Moreover, Bi2O3-WO3/rGO NCs showed improved biocompatibility in human umbilical vein endothelial cells (HUVECs) than pure WO3 NPs. The results of this work showed that Bi2O3-doped WO3 particles decorated on rGO sheets display improved photocatalytic and anticancer activity. The preliminary data warrants further research on such NCs for their applications in the environment and medicine.

Photocatalytic Degradation of Methylene Blue and Anticancer Response of In2O3/RGO Nanocomposites Prepared by a Microwave-Assisted Hydrothermal Synthesis Process.

The incorporation of graphene with metal oxide has been widely explored in various fields, including energy storage devices, optical applications, biomedical applications, and water remediation. This research aimed to assess the impact of reduced graphene oxide (RGO) doping on the photocatalytic and anticancer properties of In2O3 nanoparticles. Pure and In2O3/RGO nanocomposites were effectively synthesized using the single-step microwave hydrothermal process. XRD, TEM, SEM, EDX, XPS, Raman, UV-Vis, and PL spectroscopy were carefully utilized to characterize the prepared samples. XRD data showed that synthesized In2O3 nanoparticles had high crystallinity with a decreased crystal size after RGO doping. TEM and SEM images revealed that the In2O3 NPs were spherical and uniformly embedded onto the surface of RGO sheets. Elemental analysis of In2O3/RGO NC confirmed the presence of In, O, and C without impurities. Raman analysis indicated the successful fabrication of In2O3 onto the RGO surface. Uv-Vis analysis showed that the band gap energy was changed with RGO addition. Raman spectra confirmed that In2O3 nanoparticles were successfully anchored onto the RGO sheet. PL results indicated that the prepared In2O3/RGO NCs can be applied to enhance photocatalytic activity and biomedical applications. In the degradation experiment, In2O3/RGO NCs exhibited superior photocatalytic activity compared to that of pure In2O3. The degradation efficiency of In2O3/RGO NCs for MB dye was up to 90%. Biological data revealed that the cytotoxicity effect of In2O3/RGO NCs was higher than In2O3 NPs in human colorectal (HCT116) and liver (HepG2) cancer cells. Importantly, the In2O3/RGO NCs exhibited better biocompatibility against human normal peripheral blood mononuclear cells (PBMCs). All the results suggest that RGO addition improves the photocatalytic and anticancer activity of In2O3 NPs. This study highlights the potential of In2O3/RGO NCs as an efficient photocatalyst and therapeutic material for water remediation and biomedicine.

Bismuth Oxide (Bi2O3) Nanoparticles Cause Selective Toxicity in a Human Endothelial (HUVE) Cell Line Compared to Epithelial Cells.

A review of recent literature suggests that bismuth oxide (Bi2O3, referred to as B in this article) nanoparticles (NPs) elicit an appreciable response only after a concentration above 40-50 µg/mL in different cells all having an epithelial origin, to the best of our knowledge. Here, we report the toxicological profile of Bi2O3 NPs (or BNPs) (71 ± 20 nm) in a human endothelial cell (HUVE cell line) in which BNPs exerted much steeper cytotoxicity. In contrast to a high concentration of BNPs (40-50 µg/mL) required to stimulate an appreciable toxicity in epithelial cells, BNPs induced 50% cytotoxicity in HUVE cells at a very low concentration (6.7 µg/mL) when treated for 24 h. BNPs induced reactive oxygen species (ROS), lipid peroxidation (LPO), and depletion of the intracellular antioxidant glutathione (GSH). BNPs also induced nitric oxide (NO,) which can result in the formation of more harmful species in a fast reaction that occurs with superoxide (O2•-). Exogenously applied antioxidants revealed that NAC (intracellular GSH precursor) was more effective than Tiron (a preferential scavenger of mitochondrial O2•-) in preventing the toxicity, indicating ROS production is extra-mitochondrial. Mitochondrial membrane potential (MMP) loss mediated by BNPs was significantly less than that of exogenously applied oxidant H2O2, and MMP loss was not as intensely reduced by either of the antioxidants (NAC and Tiron), again suggesting BNP-mediated toxicity in HUVE cells is extra-mitochondrial. When we compared the inhibitory capacities of the two antioxidants on different parameters of this study, ROS, LPO, and GSH were among the strongly inhibited biomarkers, whereas MMP and NO were the least inhibited group. This study warrants further research regarding BNPs, which may have promising potential in cancer therapy, especially via angiogenesis modulation.

Biosynthesis, Characterization, and Augmented Anticancer Activity of ZrO2 Doped ZnO/rGO Nanocomposite.

Fabrication of ZnO nanoparticles (NPs) via green process has received enormous attention for its application in biomedicine. Here, a simple and cost-effective green route is reported for the synthesis of ZrO2-doped ZnO/reduced graphene oxide nanocomposites (ZnO/ZrO2/rGO NCs) exploiting ginger rhizome extract. Our aim was to improve the anticancer performance of ZnO/ZrO2/rGO NCs without toxicity to normal cells. The preparation of pure ZnO NPs, ZnO/ZrO2 NCs, and ZnO/ZrO2/rGO NCs was confirmed by transmission electron microscopy (TEM), scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDS), X-ray diffraction (XRD), photoluminescence (PL), and dynamic light scattering (DLS). XRD spectra of ZnO/ZrO2/rGO NCs exhibited two distinct sets of diffraction peaks, ZnO wurtzite structure, and ZrO2 phases (monoclinic + tetragonal). The SEM and TEM data show that ZrO2-doped ZnO particles were uniformly distributed on rGO sheets with the excellent quality of lattice fringes without alterations. PL spectra intensity and particle size of ZnO decreased after ZrO2-doping and rGO addition. DLS data demonstrated that green prepared samples show excellent colloidal stability in aqueous suspension. Biological results showed that ZnO/ZrO2/rGO NCs display around 3.5-fold higher anticancer efficacy in human lung cancer (A549) and breast cancer (MCF7) cells than ZnO NPs. A mechanistic approach suggested that the anticancer response of ZnO/ZrO2/rGO NCs was mediated via oxidative stress evident by the induction of the intracellular reactive oxygen species level and the reduction of the glutathione level. Moreover, green prepared nanostructures display good cytocompatibility in normal cell lines; human lung fibroblasts (IMR90) and breast epithelial (MCF10A) cells. However, the cytocompatibility of ZnO/ZrO2/rGO NCs in normal cells was better than those of pure ZnO NPs and ZnO/ZrO2 NCs. Augmented anticancer potential and improved cytocompatibility of ZnO/ZrO2/rGO NCs was due to ginger extract mediated beneficial synergism between ZnO, ZrO2, and rGO. This novel investigation emphasizes the significance of medicinal herb mediated ZnO-based NCs synthesis for biomedical research.

Photodeposition mediated synthesis of silver-doped indium oxide nanoparticles for improved photocatalytic and anticancer performance.

Indium oxide nanoparticles (In2O3 NPs) are being investigated for a number of applications including gas-sensing, environmental remediation, and biomedicine. We aimed to examine the effect of silver (Ag) doping on photocatalytic and anticancer activity of In2O3 NPs. The Ag-doped (2%, 4%, and 6%weight) In2O3 NPs were synthesized by the photodeposition method. Prepared samples were characterized via X-ray diffraction (XRD), transmission electron microscopy (TEM), scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS), Fourier transform infrared (FTIR), UV-Vis spectroscopy, and the photoluminescence (PL). XRD data showed that Ag-doping increases the crystallinity of In2O3 NPs. SEM and TEM images indicated that In2O3 NPs have spherical morphology with smooth surfaces, and Ag-doping increases the size without affecting the particle's shape. XPS spectra showed the oxidation state and the presence of Ag in In2O3 NPs. Band gap energy of In2O3 NPs decreases with increasing the concentration of Ag (3.41 eV to 3.12 eV). The peak intensity of PL spectra of In2O3 NPs also reduces with the increment of Ag ions suggesting the hindrance of the recombination rate of e-/h+. The photocatalytic activity was measured by the degradation of Rh B dye under UV irradiation. The degradation efficiency of Ag-doped (6%) In2O3 NPs was 92%. Biochemical data indicated that Ag-doping enhances the anticancer performance of In2O3 NPs against human lung cancer cells (A549). Moreover, Ag-doped In2O3 NPs displayed excellent biocompatibility in normal human lung fibroblasts (IMR90). Overall, this study demonstrated that Ag-doping enhances the photocatalytic activity and anticancer efficacy of In2O3 NPs. This study warrants further investigation on the environmental and biomedical applications of Ag-In2O3 NPs.

Dietary Antioxidant Curcumin Mitigates CuO Nanoparticle-Induced Cytotoxicity through the Oxidative Stress Pathway in Human Placental Cells.

The placenta is an important organ that maintains a healthy pregnancy by transporting nutrients to the fetus and removing waste from the fetus. It also acts as a barrier to protect the fetus from hazardous materials. Recent studies have indicated that nanoparticles (NPs) can cross the placental barrier and pose a health risk to the developing fetus. The high production and widespread application of copper oxide (CuO) NPs may lead to higher exposure to humans, raising concerns of health hazards, especially in vulnerable life stages, e.g., pregnancy. Oxidative stress plays a crucial role in the pathogenesis of adverse pregnancy outcomes. Due to its strong antioxidant activity, dietary curcumin can act as a therapeutic agent for adverse pregnancy. There is limited knowledge on the hazardous effects of CuO NPs during pregnancy and their mitigation by curcumin. This study aimed to investigate the preventive effect of curcumin against CuO NP-induced toxicity in human placental (BeWo) cells. CuO NPs were synthesized by a facile hydrothermal process and characterized by X-ray diffraction, scanning electron microscopy, transmission electron microscopy, and photoluminescence techniques. We observed that curcumin did not induce toxicity in BeWo cells (1-100 µg/mL for 24 h), whereas CuO NPs decreased the cell viability dose-dependently (5-200 µg/mL for 24 h). Interestingly, CuO NP-induced cytotoxicity was effectively mitigated by curcumin co-exposure. The apoptosis data also exhibited that CuO NPs modulate the expression of several genes (p53, bax, bcl-2, casp3, and casp9), the activity of enzymes (caspase-3 and -9), and mitochondrial membrane potential loss, which was successfully reverted by co-treatment with curcumin. The mechanistic study suggested that CuO-induced reactive oxygen species generation, lipid peroxidation, and higher levels of hydrogen peroxide were significantly alleviated by curcumin co-exposure. Moreover, glutathione depletion and the lower activity of antioxidant enzymes (superoxide dismutase, glutathione peroxidase, and catalase) were effectively mitigated by curcumin. We believe this is the first report exhibiting that CuO-induced toxicity in BeWo cells can be effectively alleviated by curcumin. The pharmacological potential of dietary curcumin in NP-induced toxicity during pregnancy warrants further investigation.

Combined effect of single-walled carbon nanotubes and cadmium on human lung cancer cells.

Co-exposure of widely used single-walled carbon nanotubes (SWCNTs) and ubiquitous cadmium (Cd) to humans through ambient air is unavoidable. Studies on joint toxicity of SWCNTs and Cd in human cells are scarce. We aimed to investigate the joint effects of SWCNTs and Cd in human lung epithelial (A549) cells. Results showed that SWCNTs were safe while Cd induce significant toxicity to A549 cells. Remarkably, Cd-induced cell viability reduction, lactate dehydrogenase leakage, cell cycle arrest, dysregulation of apoptotic gene (p53, bax, bcl-2, casp3, and casp9), and mitochondrial membrane potential depletion were significantly mitigated following SWCNTs co-exposure. Cd-induced intracellular level of reactive oxygen species, hydrogen peroxide, and lipid peroxidation were significantly attenuated by SWCNT co-exposure. Moreover, glutathione depletion and lower activity of antioxidant enzymes after Cd exposure were also effectively abrogated by co-exposure of SWCNTs. Inductively coupled plasma-mass spectrometry study indicated that higher adsorption of Cd on SCWNTs might decreased cellular uptake and the toxic potential of Cd in A549 cells. Our work warranted further research to explore the potential mechanism of joint effects of SWCNTs and Cd at in vivo levels.

CeO2-Zn Nanocomposite Induced Superoxide, Autophagy and a Non-Apoptotic Mode of Cell Death in Human Umbilical-Vein-Derived Endothelial (HUVE) Cells.

In this study, a nanocomposite of cerium oxide-zinc (CeO2-Zn; 26 ± 11 nm) based on the antioxidant rare-earth cerium oxide (CeO2) nanoparticles (NPs) with the modifier zinc (Zn) was synthesized by sintering method and characterized. Its bio-response was examined in human umbilical-vein-derived endothelial (HUVE) cells to get insight into the components of vascular system. While NPs of CeO2 did not significantly alter cell viability up to a concentration of 200 µg/mL for a 24 h exposure, 154 ± 6 µg/mL of nanocomposite CeO2-Zn induced 50% cytotoxicity. Mechanism of cytotoxicity occurring due to nanocomposite by its Zn content was compared by choosing NPs of ZnO, possibly the closest nanoparticulate form of Zn. ZnO NPs lead to the induction of higher reactive oxygen species (ROS) (DCF-fluorescence), steeper depletion in antioxidant glutathione (GSH) and a greater loss of mitochondrial membrane potential (MMP) as compared to that induced by CeO2-Zn nanocomposite. Nanocomposite of CeO2-Zn, on the other hand, lead to significant higher induction of superoxide radical (O2•-, DHE fluorescence), nitric oxide (NO, determined by DAR-2 imaging and Griess reagent) and autophagic vesicles (determined by Lysotracker and monodansylcadeverine probes) as compared to that caused by ZnO NP treatment. Moreover, analysis after triple staining (by annexin V-FITC, PI, and Hoechst) conducted at their respective IC50s revealed an apoptosis mode of cell death due to ZnO NPs, whereas CeO2-Zn nanocomposite induced a mechanism of cell death that was significantly different from apoptosis. Our findings on advanced biomarkers such as autophagy and mode of cell death suggested the CeO2-Zn nanocomposite might behave as independent nanostructure from its constituent ones. Since nanocomposites can behave independently of their constituent NPs/elements, by creating nanocomposites, NP versatility can be increased manifold by just manipulating existing NPs. Moreover, data in this study can furnish early mechanistic insight about the potential damage that could occur in the integrity of vascular systems.

One-Pot Synthesis of SnO2-rGO Nanocomposite for Enhanced Photocatalytic and Anticancer Activity.

Metal oxide and graphene derivative-based nanocomposites (NCs) are attractive to the fields of environmental remediation, optics, and cancer therapy owing to their remarkable physicochemical characteristics. There is limited information on the environmental and biomedical applications of tin oxide-reduced graphene oxide nanocomposites (SnO2-rGO NCs). The goal of this work was to explore the photocatalytic activity and anticancer efficacy of SnO2-rGO NCs. Pure SnO2 NPs and SnO2-rGO NCs were prepared using the one-pot hydrothermal method. X-ray diffraction (XRD), transmission electron microscopy (TEM), scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS), Fourier transform infrared (FTIR), UV-Vis spectrometry, photoluminescence (PL), and Raman scattering microscopy were applied to characterize the synthesized samples. The crystallite size of the SnO2 NPs slightly increased after rGO doping. TEM and SEM images show that the SnO2 NPs were tightly anchored onto the rGO sheets. The XPS and EDX data confirmed the chemical state and elemental composition of the SnO2-rGO NCs. Optical data suggest that the bandgap energy of the SnO2-rGO NCs was slightly lower than for the pure SnO2 NPs. In comparison to pure SnO2 NPs, the intensity of the PL spectra of the SnO2-rGO NCs was lower, indicating the decrement of the recombination rate of the surfaces charges (e-/h+) after rGO doping. Hence, the degradation efficiency of methylene blue (MB) dye by SnO2-rGO NCs (93%) was almost 2-fold higher than for pure SnO2 NPs (54%). The anticancer efficacy of SnO2-rGO NCs was also almost 1.5-fold higher against human liver cancer (HepG2) and human lung cancer (A549) cells compared to the SnO2 NPs. This study suggests a unique method to improve the photocatalytic activity and anticancer efficacy of SnO2 NPs by fusion with graphene derivatives.

Enhanced Anticancer Performance of Eco-Friendly-Prepared Mo-ZnO/RGO Nanocomposites: Role of Oxidative Stress and Apoptosis.

ZnO nanoparticles (NPs) have attracted great attention in cancer therapy because of their novel and tailorable physicochemical features. Pure ZnO NPs, molybdenum (Mo)-doped ZnO NPs, and Mo-ZnO/reduced graphene oxide nanocomposites (Mo-ZnO/RGO NCs) were prepared using a facile, inexpensive, and eco-friendly approach using date palm (Phoenix dactylifera L.) fruit extract. Anticancer efficacy of green synthesized NPs/NCs was examined in two different cancer cells. The potential mechanism of the anticancer activity of green synthesized NPs/NCs was explored through oxidative stress and apoptosis. The syntheses of pure ZnO NPs, Mo-ZnO NPs, and Mo-ZnO/RGO NCs were confirmed by X-ray diffraction (XRD), transmission electron microscopy (TEM), scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDS), and photoluminescence (PL). Dynamic light scattering (DLS) study indicated the excellent colloidal stability of green prepared samples. Mo-ZnO/RGO NCs exhibited threefold higher anticancer activity in human colon (HCT116) and breast (MCF7) cancer cells as compared to pure ZnO NPs. The anticancer activity of Mo-ZnO/RGO NCs was mediated through reactive oxygen species, p53, and the caspase-3 pathway. Moreover, cytocompatibility of Mo-ZnO/RGO NCs in human normal colon epithelial (NCM460) and normal breast epithelial cells (MCF10A) was much better than those of pure ZnO NPs. Altogether, green stabilized Mo-ZnO/RGO NCs exhibited enhanced anticancer performance and improved cytocompatibility because of green mediated good synergism between ZnO, Mo, and RGO. This study suggested the high nutritional value fruit-based facile preparation of ZnO-based nanocomposites for cancer therapy.

Facile Synthesis, Characterization, Photocatalytic Activity, and Cytotoxicity of Ag-Doped MgO Nanoparticles.

Due to unique physicochemical properties, magnesium oxide nanoparticles (MgO NPs) have shown great potential for various applications, including biomedical and environmental remediation. Moreover, the physiochemical properties of MgO NPs can be tailored by metal ion doping that can be utilized in photocatalytic performance and in the biomedical field. There is limited study on the photocatalytic activity and biocompatibility of silver (Ag)-doped MgO NPs. This study was planned for facile synthesis, characterization, and photocatalytic activity of pure and silver (Ag)-doped MgO NPs. In addition, cytotoxicity of pure and Ag-doped MgO NPs was assessed in human normal umbilical vein endothelial cells (HUVECs). Pure MgO NPs and Ag-doped (1, 2, 5, and 7.5 mol%) MgO NPs were prepared via a simple sol-gel procedure. X-ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), Fourier transform infrared (FTIR), photoluminescence (PL), and X-ray photoelectron spectroscopy (XPS) were used to characterize the prepared samples. XRD results showed the preparation of highly crystalline NPs with no impurity peaks. TEM and SEM studies indicate smooth surfaces with almost spherical morphology of MgO NPs, and Ag-doping did not change the morphology. Elemental composition study suggested that Ag is uniformly distributed in MgO particles. Intensity of the PL spectra of MgO NPs decreased with increasing the concentration of Ag dopants. In comparison to pure MgO NPs, Ag-MgO NPs showed higher degradation of methylene blue (MB) dye under UV irradiation. The improved photocatalytic activity of Ag-MgO NPs was related to the effect of dopant concentration on reducing the recombination between electrons and holes. Cytotoxicity studies showed good biocompatibility of pure and Ag-doped MgO NPs with human normal umbilical vein endothelial cells (HUVECs). These results highlighted the potential of Ag-doped MgO NPs in environmental remediation.

A Novel Green Preparation of Ag/RGO Nanocomposites with Highly Effective Anticancer Performance.

The efficacy of current cancer therapies is limited due to several factors, including drug resistance and non-specific toxic effects. Due to their tuneable properties, silver nanoparticles (Ag NPs) and graphene derivative-based nanomaterials are now providing new hope to treat cancer with minimum side effects. Here, we report a simple, inexpensive, and eco-friendly protocol for the preparation of silver-reduced graphene oxide nanocomposites (Ag/RGO NCs) using orange peel extract. This work was planned to curtail the use of toxic chemicals, and improve the anticancer performance and cytocompatibility of Ag/RGO NCs. Aqueous extract of orange peels is abundant in phytochemicals that act as reducing and stabilizing agents for the green synthesis of Ag NPs and Ag/RGO NCs from silver nitrate and graphene oxide (GO). Moreover, the flavonoid present in orange peel is a potent anticancer agent. Green-prepared Ag NPs and Ag/RGO NCs were characterized by UV-visible spectrophotometry, transmission electron microscopy (TEM), scanning electron microscopy (SEM), energy dispersive spectroscopy (EDS), X-ray diffraction (XRD), and dynamic light scattering (DLS). The results of the anticancer study demonstrated that the killing potential of Ag/RGO NCs against human breast cancer (MCF7) and lung cancer (A549) cells was two-fold that of pure Ag NPs. Moreover, the cytocompatibility of Ag/RGO NCs in human normal breast epithelial (MCF10A) cells and normal lung fibroblasts (IMR90) was higher than that of pure Ag NPs. This mechanistic study indicated that Ag/RGO NCs induce toxicity in cancer cells through pro-oxidant reactive oxygen species generation and antioxidant glutathione depletion and provided a novel green synthesis of Ag/RGO NCs with highly effective anticancer performance and better cytocompatibility.

Anti-Inflammatory CeO2 Nanoparticles Prevented Cytotoxicity Due to Exogenous Nitric Oxide Donors via Induction Rather Than Inhibition of Superoxide/Nitric Oxide in HUVE Cells.

The mechanism behind the cytoprotective potential of cerium oxide nanoparticles (CeO2 NPs) against cytotoxic nitric oxide (NO) donors and H2O2 is still not clear. Synthesized and characterized CeO2 NPs significantly ameliorated the lipopolysaccharide (LPS)-induced cytokines IL-1ß and TNF-α. The main goal of this study was to determine the capacities of NPs regarding signaling effects that could have occurred due to reactive oxygen species (ROS) and/or NO, since NP-induced ROS/NO did not lead to toxicity in HUVE cells. Concentrations that induced 50% cell death (i.e., IC50s) of two NO donors (DETA-NO; 1250 ± 110 µM and sodium nitroprusside (SNP); 950 ± 89 µM) along with the IC50 of H2O2 (120 ± 7 µM) were utilized to evaluate cytoprotective potential and its underlying mechanism. We determined total ROS (as a collective marker of hydrogen peroxide, superoxide radical (O2•-), hydroxyl radical, etc.) by DCFH-DA and used a O2•- specific probe DHE to decipher prominent ROS. The findings revealed that signaling effects mediated mainly by O2•- and/or NO are responsible for the amelioration of toxicity by CeO2 NPs at 100 µg/mL. The unaltered effect on mitochondrial membrane potential (MMP) due to NP exposure and, again, CeO2 NPs-mediated recovery in the loss of MMP due to exogenous NO donors and H2O2 suggested that NP-mediated O2•- production might be extra-mitochondrial. Data on activated glutathione reductase (GR) and unaffected glutathione peroxidase (GPx) activities partially explain the mechanism behind the NP-induced gain in GSH and persistent cytoplasmic ROS. The promoted antioxidant capacity due to non-cytotoxic ROS and/or NO production, rather than inhibition, by CeO2 NP treatment may allow cells to develop the capacity to tolerate exogenously induced toxicity.

Facile Synthesis of Zn-Doped Bi2O3 Nanoparticles and Their Selective Cytotoxicity toward Cancer Cells.

Bismuth (III) oxide nanoparticles (Bi2O3 NPs) have shown great potential for biomedical applications because of their tunable physicochemical properties. In this work, pure and Zn-doped (1 and 3 mol %) Bi2O3 NPs were synthesized by a facile chemical route and their cytotoxicity was examined in cancer cells and normal cells. The X-ray diffraction results show that the tetragonal phase of ß-Bi2O3 remains unchanged after Zn-doping. Transmission electron microscopy and scanning electron microscopy images depicted that prepared particles were spherical with smooth surfaces and the homogeneous distribution of Zn in Bi2O3 with high-quality lattice fringes without distortion. Photoluminescence spectra revealed that intensity of Bi2O3 NPs decreases with increasing level of Zn-doping. Biological data showed that Zn-doped Bi2O3 NPs induce higher cytotoxicity to human lung (A549) and liver (HepG2) cancer cells as compared to pure Bi2O3 NPs, and cytotoxic intensity increases with increasing concentration of Zn-doping. Mechanistic data indicated that Zn-doped Bi2O3 NPs induce cytotoxicity in both types of cancer cells through the generation of reactive oxygen species and caspase-3 activation. On the other hand, biocompatibility of Zn-doped Bi2O3 NPs in normal cells (primary rat hepatocytes) was greater than that of pure Bi2O3 NPs and biocompatibility improves with increasing level of Zn-doping. Altogether, this is the first report highlighting the role of Zn-doping in the anticancer activity of Bi2O3 NPs. This study warrants further research on the antitumor activity of Zn-doped Bi2O3 NPs in suitable in vivo models.

Pt-Coated Au Nanoparticle Toxicity Is Preferentially Triggered Via Mitochondrial Nitric Oxide/Reactive Oxygen Species in Human Liver Cancer (HepG2) Cells.

Reactive nitrogen species (RNS) that are formed from the reaction of versatile nitric oxide (NO) with reactive oxygen species (ROS) have been less explored in potential cancer therapy. This may be partly due to the fewer available agents that could induce NO in cells. Here, we report platinum-coated gold nanoparticles (Pt-coated Au NPs; 27 ± 20 nm) as a strong inducer of NO (assessed by live-cell imaging under NO-specific DAR-1 probe labeling and indirectly using a Griess reagent) in human liver carcinoma (HepG2) cells. In addition to NO, this study found a critical role of ROS from mitochondrial sources in the mechanism of toxicity caused by Pt-coated Au NPs. Cotreatment with a thiol-replenishing general antioxidant NAC (N-acetyl cysteine) led to significant amelioration of oxidative stress against NP-induced toxicity. However, NAC did not exhibit as much ameliorative potential against NP-induced oxidative stress as the superoxide radical (O2•-)-scavenging mitochondrial specific antioxidant mito-TEMPO did. The higher protective potential of mito-TEMPO in comparison to NAC reveals mitochondrial ROS as an active mediator of NP-induced toxicity in HepG2 cells. Moreover, the relatively unaltered NP-induced NO concentration under cotreatment of GSH modulators NAC and buthionine sulfoximine (BSO) suggested that NO production due to NP treatment is rather independent of the cellular thiols at least in HepG2 cells. Moreover, toxicity potentiation by exogenous H2O2 again suggested a more direct involvement of ROS/RNS in comparison to the less potentiation of toxicity due to GSH-exhausting BSO. A steeper amelioration in NP-induced NO and ROS and, consequently, cytotoxicity by mito-TEMPO in comparison to NAC reveal a pronounced role of NO and ROS via the mitochondrial pathway in the toxicity of Pt-coated Au NPs in HepG2 cells.

SnO2-Doped ZnO/Reduced Graphene Oxide Nanocomposites: Synthesis, Characterization, and Improved Anticancer Activity via Oxidative Stress Pathway.

BACKGROUND: Therapeutic selectivity and drug resistance are critical issues in cancer therapy. Currently, zinc oxide nanoparticles (ZnO NPs) hold considerable promise to tackle this problem due to their tunable physicochemical properties. This work was designed to prepare SnO2-doped ZnO NPs/reduced graphene oxide nanocomposites (SnO2-ZnO/rGO NCs) with enhanced anticancer activity and better biocompatibility than those of pure ZnO NPs. MATERIALS AND METHODS: Pure ZnO NPs, SnO2-doped ZnO (SnO2-ZnO) NPs, and SnO2-ZnO/rGO NCs were prepared via a facile hydrothermal method. Prepared samples were characterized by field emission transmission electron microscopy (FETEM), energy dispersive spectroscopy (EDS), field emission scanning electron microscopy (FESEM), X-ray diffraction (XRD), ultraviolet-visible (UV-VIS) spectrometer, and dynamic light scattering (DLS) techniques. Selectivity and anticancer activity of prepared samples were assessed in human breast cancer (MCF-7) and human normal breast epithelial (MCF10A) cells. Possible mechanisms of anticancer activity of prepared samples were explored through oxidative stress pathway. RESULTS: XRD spectra of SnO2-ZnO/rGO NCs confirmed the formation of single-phase of hexagonal wurtzite ZnO. High resolution TEM and SEM mapping showed homogenous distribution of SnO2 and rGO in ZnO NPs with high quality lattice fringes without any distortion. Band gap energy of SnO2-ZnO/rGO NCs was lower compared to SnO2-ZnO NPs and pure ZnO NPs. The SnO2-ZnO/rGO NCs exhibited significantly higher anticancer activity against MCF-7 cancer cells than those of SnO2-ZnO NPs and ZnO NPs. The SnO2-ZnO/rGO NCs induced apoptotic response through the upregulation of caspase-3 gene and depletion of mitochondrial membrane potential. Mechanistic study indicated that SnO2-ZnO/rGO NCs kill cancer cells through oxidative stress pathway. Moreover, biocompatibility of SnO2-ZnO/rGO NCs was also higher against normal breast epithelial (MCF10A cells) in comparison to SnO2-ZnO NPs and ZnO NPs. CONCLUSION: SnO2-ZnO/rGO NCs showed enhanced anticancer activity and better biocompatibility than SnO2-ZnO NPs and pure ZnO NPs. This work suggested a new approach to improve the selectivity and anticancer activity of ZnO NPs. Studies on antitumor activity of SnO2-ZnO/rGO NCs in animal models are further warranted.

Co-exposure of Bi2O3 nanoparticles and bezo[a]pyrene-enhanced in vitro cytotoxicity of mouse spermatogonia cells.

Recent attention has been focused on reproductive toxicity of nanoscale materials in combination with pre-existing environmental pollutants. Due to its unique characteristics, bismuth (III) oxide (Bi2O3) nanoparticles (BONPs) are being used in diverse fields including cosmetics and biomedicine. Benzo[a]pyrene (BaP) is a known endocrine disruptor that most common sources of BaP exposure to humans are cigarette smoke and well-cooked barbecued meat. Hence, joint exposure of BONPs and BaP in humans is common. There is scarcity of information on toxicity of BONPs in combination with BaP in human reproductive system. In this work, combined effects of BONPs and BaP in mouse spermatogonia (GC-1 spg) cells were assessed. Results showed that combined exposure of BONPs and BaP synergistically induced cell viability reduction, lactate dehydrogenase leakage, induction of caspases (-3 and -9) and mitochondrial membrane potential loss in GC-1 spg cells. Co-exposure of BONPs and BaP also synergistically induced production of pro-oxidants (reactive oxygen species and hydrogen peroxide) and reduction of antioxidants (glutathione and several antioxidant enzymes). Experiments with N-acetyl-cysteine (NAC, a reactive oxygen species scavenger) indicated that oxidative stress was a plausible mechanism of synergistic toxicity of BONPs and BaP in GC-1 spg cells. Present data could be helpful for future in vivo research and risk assessment of human reproductive system co-exposed to BONPs and BaP.

Barium Titanate (BaTiO3) Nanoparticles Exert Cytotoxicity through Oxidative Stress in Human Lung Carcinoma (A549) Cells.

Barium titanate (BaTiO3) nanoparticles (BT NPs) have shown exceptional characteristics such as high dielectric constant and suitable ferro-, piezo-, and pyro-electric properties. Thus, BT NPs have shown potential to be applied in various fields including electro-optical devices and biomedicine. However, very limited knowledge is available on the interaction of BT NPs with human cells. This work was planned to study the interaction of BT NPs with human lung carcinoma (A549) cells. Results showed that BT NPs decreased cell viability in a dose- and time-dependent manner. Depletion of mitochondrial membrane potential and induction of caspase-3 and -9 enzyme activity were also observed following BT NP exposure. BT NPs further induced oxidative stress indicated by induction of pro-oxidants (reactive oxygen species and hydrogen peroxide) and reduction of antioxidants (glutathione and several antioxidant enzymes). Moreover, BT NP-induced cytotoxicity and oxidative stress were effectively abrogated by N-acetyl-cysteine (an ROS scavenger), suggesting that BT NP-induced cytotoxicity was mediated through oxidative stress. Intriguingly, the underlying mechanism of cytotoxicity of BT NPs was similar to the mode of action of ZnO NPs. At the end, we found that BT NPs did not affect the non-cancerous human lung fibroblasts (IMR-90). Altogether, BT NPs selectively induced cytotoxicity in A549 cells via oxidative stress. This work warrants further research on selective cytotoxicity mechanisms of BT NPs in different types of cancer cells and their normal counterparts.

Single-Walled Carbon Nanotubes Attenuate Cytotoxic and Oxidative Stress Response of Pb in Human Lung Epithelial (A549) Cells.

Combined exposure of single-walled carbon nanotubes (SWCNTs) and trace metal lead (Pb) in ambient air is unavoidable. Most of the previous studies on the toxicity of SWCNTs and Pb have been conducted individually. There is a scarcity of information on the combined toxicity of SWCNTs and Pb in human cells. This work was designed to explore the combined effects of SWCNTs and Pb in human lung epithelial (A549) cells. SWCNTs were prepared through the plasma-enhanced vapor deposition technique. Prepared SWCNTs were characterized by x-ray diffraction, x-ray photoelectron spectroscopy, scanning electron microscopy, and dynamic light scattering. We observed that SWCNTs up to a concentration of 100 µg/mL was safe, while Pb induced dose-dependent (5-100 µg/mL) cytotoxicity in A549 cells. Importantly, cytotoxicity, cell cycle arrest, mitochondrial membrane potential depletion, lipid peroxidation, and induction of caspase-3 and -9 enzymes following Pb exposure (50 µg/mL for 24 h) were efficiently attenuated by the co-exposure of SWCNTs (10 µg/mL for 24 h). Furthermore, generation of Pb-induced pro-oxidants (reactive oxygen species and hydrogen peroxide) and the reduction of antioxidants (antioxidant enzymes and glutathione) were also mitigated by the co-exposure of SWCNTs. Inductively coupled plasma-mass spectrometry results suggest that the adsorption of Pb on the surface of SWCNTs could attenuate the bioavailability and toxicity of Pb in A549 cells. Our data warrant further research on the combined effects of SWCNTs and Pb in animal models.

Gadolinium Oxide Nanoparticles Induce Toxicity in Human Endothelial HUVECs via Lipid Peroxidation, Mitochondrial Dysfunction and Autophagy Modulation.

In spite of the potential preclinical advantage of Gd2O3 nanoparticles (designated here as GO NPs) over gadolinium-based compounds in MRI, recent concerns of gadolinium deposits in various tissues undergoing MRI demands a mechanistic investigation. Hence, we chose human to measure umbilical vein endothelial cells (HUVECs) that line the vasculature and relevant biomarkers due to GO NPs exposure in parallel with the NPs of ZnO as a positive control of toxicity. GO NPs, as measured by TEM, had an average length of 54.8 ± 29 nm and a diameter of 13.7 ± 6 nm suggesting a fiber-like appearance. With not as pronounced toxicity associated with a 24-h exposure, GO NPs induced a concentration-dependent cytotoxicity (IC50 = 304 ± 17 µg/mL) in HUVECs when exposed for 48 h. GO NPs emerged as significant inducer of lipid peroxidation (LPO), reactive oxygen species (ROS), mitochondrial membrane potential (MMP) and autophagic vesicles in comparison to that caused by ZnO NPs at its IC50 for the same exposure time (48 h). While ZnO NPs clearly appeared to induce apoptosis, GO NPs revealed both apoptotic as well as necrotic potentials in HUVECs. Intriguingly, the exogenous antioxidant NAC (N-acetylcysteine) co-treatment significantly attenuated the oxidative imbalance due to NPs preventing cytotoxicity significantly.