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.

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.

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.

Alleviating effects of reduced graphene oxide against lead-induced cytotoxicity and oxidative stress in human alveolar epithelial (A549) cells.

Broad application of reduced graphene oxide (rGO) and ubiquitous lead (Pb) pollution may increase the possibility of combined exposure of humans. Information on the combined effects of rGO and Pb in human cells is scarce. This work was designed to explore the potential effects of rGO on Pb-induced toxicity in human alveolar epithelial (A549) cells. Prepared rGO was polycrystalline in nature. The formation of a few layers of visible creases and silky morphology due to high aspect ratio was confirmed. Low level (25 µg/mL) of rGO was not toxic to A549 cells. However, Pb exposure (25 µg/mL) induced cell viability reduction, lactate dehydrogenase enzyme leakage with rounded morphology in A549 cells. Remarkably, Pb-induced cytotoxicity was significantly mitigated by rGO co-exposure. Pb-induced mitochondrial membrane potential loss, cell cycle arrest and higher activity of caspase-3 and -9 enzymes were also alleviated by rGO co-exposure. Moreover, we observed that Pb exposure causes generation of pro-oxidants (e.g., reactive oxygen species, hydrogen peroxide and lipid peroxidation) and antioxidant depletion (e.g., glutathione and antioxidant enzymes). In addition, the effects of Pb on pro-oxidant and antioxidant markers were significantly reverted by GO co-exposure. Inductively coupled plasma-mass spectrometry suggested that due to the adsorption of Pb on rGO sheets, accessibility of Pb ions for A549 cells was limited. Hence, rGO reduced the toxicity of Pb in A549 cells. This research warrants further study to work on detailed underlying mechanisms of the mitigating effects of rGO against Pb-induced toxicity on a molecular level.

Influence of silica nanoparticles on cadmium-induced cytotoxicity, oxidative stress, and apoptosis in human liver HepG2 cells.

Extensive application of amorphous silica nanoparticles (Si NPs) and ubiquitous cadmium (Cd) may increase their chances of coexposure to humans. Studies on combined effects of Si NPs and Cd in human cells are very limited. We investigated the potential mechanism of toxicity caused by coexposure of amorphous Si NPs and Cd in human liver (HepG2) cells. Results showed that Si NPs were not toxic to HepG2. However, Cd induced significant toxicity in HepG2 cells. Interestingly, we observed that a noncytotoxic concentration of Si NPs potentiated the cytotoxicity of Cd in HepG2 cells. We further noticed that coexposure of Si NPs and Cd augmented oxidative stress evidenced by the generation of oxidants (reactive oxygen species, hydrogen peroxide, and lipid peroxidation) and depletion of antioxidants (glutathione level and antioxidant enzyme activity). Coexposure of Si NPs and Cd also augmented mitochondria-mediated apoptosis in HepG2 cells indicated by altered regulation of apoptotic genes (p53, bax, bcl-2, caspase-3, and caspase-9) along with reduced mitochondrial membrane potential. Interaction data indicated that Si NPs facilitate the cellular uptake of Cd due to its strong adsorption on the surface of Si NPs. Hence, Si NPs increased the bioaccumulation and toxicity of Cd in HepG2 cells. This study warrants further research to explore the potential mechanisms of combined toxicity of Si NPs and Cd in animal models.

High Surface Reactivity and Biocompatibility of Y2O3 NPs in Human MCF-7 Epithelial and HT-1080 FibroBlast Cells.

This study aimed to generate a comparative data on biological response of yttrium oxide nanoparticles (Y2O3 NPs) with the antioxidant CeO2 NPs and pro-oxidant ZnO NPs. Sizes of Y2O3 NPs were found to be in the range of 35±10 nm as measured by TEM and were larger from its hydrodynamic sizes in water (1004 ± 134 nm), PBS (3373 ± 249 nm), serum free culture media (1735 ± 305 nm) and complete culture media (542 ± 108 nm). Surface reactivity of Y2O3 NPs with bovine serum albumin (BSA) was found significantly higher than for CeO2 and ZnO NPs. The displacement studies clearly suggested that adsorption to either BSA, filtered serum or serum free media was quite stable, and was dependent on whichever component interacted first with the Y2O3 NPs. Enzyme mimetic activity, like that of CeO2 NPs, was not detected for the NPs of Y2O3 or ZnO. Cell viability measured by MTT and neutral red uptake (NRU) assays suggested Y2O3 NPs were not toxic in human breast carcinoma MCF-7 and fibroblast HT-1080 cells up to the concentration of 200 µg/mL for a 24 h treatment period. Oxidative stress markers suggested Y2O3 NPs to be tolerably non-oxidative and biocompatible. Moreover, mitochondrial potential determined by JC-1 as well as lysosomal activity determined by lysotracker (LTR) remained un-affected and intact due to Y2O3 and CeO2 NPs whereas, as expected, were significantly induced by ZnO NPs. Hoechst-PI dual staining clearly suggested apoptotic potential of only ZnO NPs. With high surface reactivity and biocompatibility, NPs of Y2O3 could be a promising agent in the field of nanomedicine.

Mechanism of ROS scavenging and antioxidant signalling by redox metallic and fullerene nanomaterials: Potential implications in ROS associated degenerative disorders.

BACKGROUND: The balance between oxidation and anti-oxidation is believed to be critical in maintaining healthy biological systems. However, our endogenous antioxidant defense systems are incomplete without exogenous antioxidants and, therefore, there is a continuous demand for exogenous antioxidants to prevent stress and ageing associated disorders. Nanotechnology has yielded enormous variety of nanomaterials (NMs) of which metallic and carbonic (mainly fullerenes) NMs, with redox property, have been found to be strong scavengers of ROS and antioxidants in preclinical in vitro and in vivo models. SCOPE OF REVIEW: Redox activity of metal based NMs and membrane translocation time of fullerene NMs seem to be the major determinants in ROS scavenging potential exhibited by these NMs. A comprehensive knowledge about the effects of ROS scavenging NMs in cellular antioxidant signalling is largely lacking. This review compiles the mechanisms of ROS scavenging as well as antioxidant signalling of the aforementioned metallic and fullerene NMs. MAJOR CONCLUSIONS: Direct interaction between NMs and proteins does greatly affect the corona/adsorption formation dynamics but such interaction does not provide the explanation behind diverse biological outcomes induced by NMs. Indirect interaction, however, that could occur via NMs uptake and dissolution, NMs ROS induction and ROS scavenging property, and NMs membrane translocation time seem to work as a central mode of interaction. GENERAL SIGNIFICANCE: The usage of potential antioxidant NMs in biological systems would greatly impact the field of nanomedicine. ROS scavenging NMs hold great promise in the future treatment of ROS related degenerative disorders.

Differential cytotoxicity of copper ferrite nanoparticles in different human cells.

Copper ferrite nanoparticles (NPs) have the potential to be applied in biomedical fields such as cell labeling and hyperthermia. However, there is a lack of information concerning the toxicity of copper ferrite NPs. We explored the cytotoxic potential of copper ferrite NPs in human lung (A549) and liver (HepG2) cells. Copper ferrite NPs were crystalline and almost spherically shaped with an average diameter of 35 nm. Copper ferrite NPs induced dose-dependent cytotoxicity in both types of cells, evident by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide and neutral red uptake assays. However, we observed a quite different susceptibility in the two kinds of cells regarding toxicity of copper ferrite NPs. Particularly, A549 cells showed higher susceptibility against copper ferrite NP exposure than those of HepG2 cells. Loss of mitochondrial membrane potential due to copper ferrite NP exposure was observed. The mRNA level as well as activity of caspase-3 enzyme was higher in cells exposed to copper ferrite NPs. Cellular redox status was disturbed as indicated by induction of reactive oxygen species (oxidant) generation and depletion of the glutathione (antioxidant) level. Moreover, cytotoxicity induced by copper ferrite NPs was efficiently prevented by N-acetylcysteine treatment, which suggests that reactive oxygen species generation might be one of the possible mechanisms of cytotoxicity caused by copper ferrite NPs. To the best of our knowledge, this is the first report showing the cytotoxic potential of copper ferrite NPs in human cells. This study warrants further investigation to explore the mechanisms of differential toxicity of copper ferrite NPs in different types of cells. Copyright © 2016 John Wiley & Sons, Ltd.

Cytotoxic response of platinum-coated gold nanorods in human breast cancer cells at very low exposure levels.

Because of unique optical behavior gold nanorods (GNRs) have attracted attention for the application in biomedical field such as bio-sensing, bio-imaging and hyperthermia. However, toxicological response of GNRs is controversial due to their different surface coating. Therefore, a comprehensive knowledge about toxicological profile of GNRs is necessary before their biomedical applications. First time, we investigated the toxic response of GNRs coated with platinum (GNRs-Pt) in human breast carcinoma (MCF-7) cells. Platinum coating further improves the optical and catalytic properties of GNRs. Assays such as 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide (MTT), neutral red uptake (NRU) and lactate dehydroganase (LDH) assays have shown that GNRs-Pt induced cytotoxicity at very low exposure levels (0.1-0.8 µg mL-1 ). Accumulation of cells in SubG1 phase and low mitochondrial membrane potential (JC-1 probe) in treated cells suggest that GNRs-Pt induced cell death via apoptotic pathway. Quantitative real-time PCR data demonstrated that mRNA expression of apoptotic genes (bax, caspase-3 and caspase-9) were up-regulated while anti-apoptotic gene bcl-2 was down-regulated in cells exposed to GNRs-Pt. We further observed the higher activity of caspase-3 and caspase-9 enzymes in GNRs-Pt treated cells supporting mRNA data. Moreover, N-acetyl cysteine (NAC) significantly attenuated the ROS generation and cytotoxicity induced by GNRs-Pt in MCF-7 cells suggesting that ROS might plays a crucial role in GNRs-Pt induced toxicity. This study warns of possible toxicity of GNRs even at very low exposure levels. Further investigations needed to explore potential mechanisms of this low dose toxicity phenomenon. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1344-1356, 2016.

Selective cancer-killing ability of metal-based nanoparticles: implications for cancer therapy.

There has been little focus on the promising ability of metal-based nanoparticles (NPs) to kill cancer cells while sparing normal cells. Many in vitro and in vivo reports suggest that certain metal-based NPs are able to induce apoptosis and autophagy in cancer cells at specific concentrations that are not significantly toxic to non-cancerous cells. Those NPs are thought to exploit the oxidative stress conditions that prevail in cancer cells, which are largely exhausted of antioxidant ability. This review considers the induction of reactive oxygen species (ROS) by metal-based NPs as a mechanism for the specific killing of cancer cells. The article concomitantly provides a comprehensive description of the important pathways and molecules leading to programmed cell death (PCD), which occurs mainly via apoptosis, autophagy, and necroptosis. The PCD pathways are followed as ROS-burdened cancer cells succumb to ROS-generating metal-based NPs. Exploration of nanotechnology interventions in anticancer therapy demands further research into the mechanism of intracellular induction of ROS by metal-based NPs. Furthermore, the induction of ROS by NPs should be strictly controlled if ROS-based therapy is to become a paradigm in cancer therapy.

Cytotoxicity and apoptosis induction by nanoscale talc particles from two different geographical regions in human lung epithelial cells.

We have characterized the physicochemical properties of nanotalc particles from two different geographical regions and examined their toxicity mechanisms in human lung epithelial (A549) cells. Indigenous nanotalc (IN) of Indian origin and commercial nanotalc (CN) of American origin were used in this study. Physicochemical properties of nanotalc particles were characterized by X-ray diffraction (XRD), transmission electron microscopy (TEM), energy dispersive X-ray spectroscopy (EDS), Brunauer-Emmet-Teller (BET), and dynamic light scattering (DLS). Results showed that both IN and CN particles significantly induce cytotoxicity and alteration in cell cycle phases. Both IN and CN particles were found to induce oxidative stress indicated by induction of reactive oxygen species (ROS), lipid peroxidation, and depletion of antioxidant levels. DNA fragmentation and caspase-3 enzyme activation due to IN and CN particles exposure were also observed. We further showed that after iron chelation, IN and CN particles produce significantly less cytotoxicity, oxidative stress, and genotoxicity to A549 cells as compared with nonchelated particles. In conclusion, this study demonstrated that redox active iron plays significant role in the toxicity of IN and CN particles, which may be mediated through ROS generation and oxidative stress.

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.

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.

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.

Apoptosis induction by silica nanoparticles mediated through reactive oxygen species in human liver cell line HepG2.

Silica nanoparticles are increasingly utilized in various applications including agriculture and medicine. In vivo studies have shown that liver is one of the primary target organ of silica nanoparticles. However, possible mechanisms of hepatotoxicity caused by silica nanoparticles still remain unclear. In this study, we explored the reactive oxygen species (ROS) mediated apoptosis induced by well-characterized 14nm silica nanoparticles in human liver cell line HepG2. Silica nanoparticles (25-200µg/ml) induced a dose-dependent cytotoxicity in HepG2 cells. Silica nanoparticles were also found to induce oxidative stress in dose-dependent manner indicated by induction of ROS and lipid peroxidation and depletion of glutathione (GSH). Quantitative real-time PCR and immunoblotting results showed that both the mRNA and protein expressions of cell cycle checkpoint gene p53 and apoptotic genes (bax and caspase-3) were up-regulated while the anti-apoptotic gene bcl-2 was down-regulated in silica nanoparticles treated cells. Moreover, co-treatment of ROS scavenger vitamin C significantly attenuated the modulation of apoptotic markers along with the preservation of cell viability caused by silica nanoparticles. Our data demonstrated that silica nanoparticles induced apoptosis in human liver cells, which is ROS mediated and regulated through p53, bax/bcl-2 and caspase pathways. This study suggests that toxicity mechanisms of silica nanoparticles should be further investigated at in vivo level.

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.