A simple chemical reduction approach to dope ß-FeSi2 with boron and its comprehensive characterization.

ß-FeSi2 has been doped with Boron via a novel and cost-effective chemical reduction of the glassy phase of [(Fe2O3 + 4SiO2 + B2O3 + FeBO3 + Fe2SiO4)] using Mg metal at 800 °C. Doped ß-FeSi2 has been investigated via extensive characterization and detailed analysis using first-principles calculations. The reduction in the d-spacing as can be observed from the XRD peak shift as well as the blue shift of the ß-Raman line along with the right shift of Si and Fe 2p peaks indicate the B doping. The Hall investigation basically demonstrates p-type conductivity. Hall parameters were also analyzed using thermal mobility and dual-band model. The temperature profile of RH demonstrates the contribution of shallow acceptor levels at low temperatures, whereas the deep acceptor level contributes at high temperatures. Dual-band investigation reveals a substantial increase in the Hall concentration with B doping due to the cumulative contribution of both deep and shallow acceptor levels. The low-temperature mobility profile exhibits phonon and ionized impurity scattering just above and below 75 K, respectively. Moreover, it demonstrates that holes in low-doped samples can be transported more easily than at higher B doping. From density functional theory (DFT) calculations, the origin of the dual-band model has been validated from the electronic structure of ß-FeSi2. Further, the effects of Si and Fe vacancies and B doping on the electronic structure of ß-FeSi2 have also been demonstrated. The charge transfer to the system due to B doping has indicated that an increase in doping leads to higher p-type characteristics.

Maleic and L-tartaric acids as new anti-sprouting agents for potatoes during storage in comparison to other efficient sprout suppressants.

Inhibiting sprouting of potatoes is an interesting subject needed for potato storage and industry. Sprouting degrades the quality of tuber along with releasing α-solanine and α-chaconine, which are harmful for health. Sprout suppressants, available in the market, are either costly or toxic to both health and environment. So, there is a need for developing countries to explore new sprouting suppressant compound which is cheap, non-toxic and reasonably efficient in comparison to commercial ones. We have established that simple maleic acid and L-tartaric acid are effective sprout suppressing agents. Both can hinder sprouting up to 6 weeks and 4 weeks post treatment respectively at room temperature in dark. These do not affect the quality parameters, retain the moisture content and maintain the stout appearance of the tubers along the total storage period. Thus maleic acid and L-tartaric acid would qualify as alternative, cheap, efficient sprout suppressant for potato storage and processing.

Substitutional Doping of MoS2 for Superior Gas-Sensing Applications: A Proof of Concept.

Two-dimensional layered materials (like MoS2 and WS2) those are being used as sensing layers in chemoresistive gas sensors suffer from poor sensitivity and selectivity. Mere surface functionalization (decorating of material surface) with metal nanoparticles (NPs) might not improve the sensor performance significantly. In this respect, doping of the layered material can play a significant role. Here, we report a simple yet effective substitutional doping technique to dope MoS2 with noble metals. Through various material characterization techniques like X-ray diffraction, scanning tunneling spectroscopy images, and selected area electron diffraction pattern, we were able to put forward the difference between surface decoration and substitutional doping by Au at S-vacancy sites of MoS2. Lattice strain was found to exist in the Au-doped MoS2 samples, while being absent in the Au NP-decorated samples. Surface chemistry studies performed using X-ray photoelectron spectroscopy showed a shift of Mo 3d peaks to lower binding energies, thus realizing p-type doping due to Au. The blue shift of the peaks as observed in Raman spectroscopy further confirmed the p-type doping. We found that gold-doped MoS2 was more sensitive and selective toward ammonia (with a response of 150% for 500 ppm of ammonia at 90 °C) as compared to gold NP-decorated MoS2. The advantages of substitutional doping and the gas-sensing mechanism were also explained by the density functional theory study. From the first principles study, it was found that the adsorption of Au atoms on the S-vacancy site of a monolayer of the MoS2 sheet was thermodynamically favorable with the adsorption energy of 2.39 eV. We also successfully doped MoS2 with Pt using the same technique. It was found that Pt-doped MoS2 gives huge response toward humidity (60,000% at 80% relative humidity). Thus, various noble metal doping of MoS2 selectively improved the sensing response toward specific analytes. From this work, we believe that this method could also be useful to dope other layered nanomaterials to design gas sensors with improved selectivity.

A novel nano-anti-malarial induces redox damage and elicits cytokine response to the parasite.

Emergence and spread of resistant parasites to the newest chemotherapeutic anti-malarial agents are the biggest challenges against malaria control programs. Therefore, developing a novel effective treatment to reduce the overgrowing burden of multidrug resistant malaria is a pressing need. Herein, we have developed a biocompatible and biodegradable, non-toxic chitosan-tripolyphosphate-chloroquine (CS-TPP CQ) nanoparticle. CS-TPP CQ nanoparticles effectively kill the parasite through redox generation and induction of the pro- and anti-inflammatory cytokines in both sensitive and resistant parasite in vitro. The in vitro observations showed a strong inhibitory effect (p < 0.01) on pro-inflammatory cytokines more specifically on TNF-α and IFN-γ whereas CS-TPP CQ nanoparticles significantly elevated the anti-inflammatory cytokines- IL-10 and TGF-ß. In addition, CS-TPP CQ nanoparticle significantly increased NO generation (p < 0.01) and altered the GSH/GSSG ratio 72 h after parasite co-culture with peripheral blood mononuclear cells culminating in the free radical induced parasite killing. CS-TPP CQ nanoparticle had an effective dose of 100 ng/ml against CQ-sensitive parasite lines (p < 0.001) whereas effective dose against CQ-resistant parasite line was 200 ng/ml CS-TPP CQ with an effective duration of 72 h (p < 0.001). Our studies suggest that CS-TPP CQ nanoparticle has a potential to modulate the pro- and anti-inflammatory responses, and to trigger the redox-mediated parasite killing. It can be a novel nano-based futuristic approach towards malaria control.

Simultaneous voltammetric determination of Adrenaline and Tyrosine in real samples by neodymium oxide nanoparticles grafted graphene.

Nd2O3 nanoparticle grafted graphene nanocomposite (NOGG) was synthesized by sonochemical treatment of an ethanolic dispersion of Nd2O3 nanoparticle and graphene. All the synthesized materials were characterized by XRD, FESEM, TEM, and BET. The NOGG has a high specific surface area (272 m2g-1) with narrowly distributed pores with diameter centered at 2.8, 6.0 and 7.50 nm. A composite paste electrode of 1:1 (w/w) NOGG and graphite was showed better electrochemical properties. The NOGG/GP electrode showed all around better electrocatalytic activity towards Adrenaline (AD) and Tyrosine (TY) than TRG/GP and bare GP electrode. According to cyclic voltammograms, AD and TY oxidized irreversibly through adsorption control process. DPV peak currents were measured at 378 ±â€¯15 mV and 787 ±â€¯15 mV for determination AD and TY respectively using the NOGG/GP electrode as the peak intensities were highest at those potentials. Under the optimized experimental condition, the determination ranges for AD and TY showed two linear ranges, those were 0.1-5-130 µM and 0.1-3-120 µM, respectively. A detection limit of AD and TY was measured (m-LOD) to be 50 nM and 40 nM, respectively. The modified electrode was reproducible, selective, highly sensitive and also employed for analysis of AD and TY in biological and pharmaceutical samples with excellent recovery.

Electrochemical detection of paracetamol and dopamine molecules using nano-particles of cobalt ferrite and manganese ferrite modified with graphite.

Some electrodes for efficient detection of paracetamol and dopamine were developed from nano sized material of cobalt ferrite (np-CoFe2O4) and manganese ferrite (np-MnFe2O4). These oxides were synthesized by combustion method using cobalt nitrate, manganese acetate and ferric nitrate as precursors in the presence of sugar and ethanolamine. The crystallite size, shape and morphology of nano material were characterized by X-ray diffraction pattern (XRD), field emission scanning electron microscopy (FESEM) and energy-dispersive X-ray spectroscopy (EDS) techniques. The crystallite sizes of synthesized nano-particles (nps) were in the range from 10 to 12 nm (calculated using Debye-Scherrer equation) with cubic crystal system. These particles were utilized as electrode modified with graphite for simultaneous detection of paracetamol and dopamine through cyclic voltammetry and Differential pulse voltammetry techniques and was found to be superior to reported literatures. The minimum detection limit of paracetamol and dopamine at CoFe2O4/GP electrode were 250 nM and 350 nM while at MnFe2O4/GP electrode it was 300 nM and 400 nM, respectively. Both the electrodes exhibited the linearity range from3 µM to 200 µM & 3 µM-160 µM for paracetamol and 3 µM-180 µM & 5 µM to 200 for dopamine, respectively. Two oxidation peaks of paracetamol and dopamine were well separated in phosphate buffer (pH = 6) in mixture with 100 mVs-1 and 50 mVs-1 scan rate for cyclic voltammetry and Differential pulse voltammetry, respectively. Both the electrodes demonstrated satisfactory results in real samples of paracetamol and dopamine.

Sol-gel synthesis of cubic titanium dioxide nanoparticle using poly(ethylene glycol) as a capping agent: voltammetric simultaneous determination of uric acid and guanine.

Titanium dioxide nanoparticles (NPs) were synthesized by a sol-gel method from hexafluorotitanic acid using poly(ethylene glycol) as a capping agent. The crystal structure and morphology of the NPs were characterized by X-ray diffraction, FESEM, and TEM. The NPs were used to modify a graphite paste electrode for simultaneous determination of uric acid (UA) and guanine (GU). The effect of calcination temperature on crystal structure and electrocatalytic activity was investigated. The electrochemical responses to UA and GU at bare GP, TiO2-350/GP, and TiO2-600/GP electrodes were compared. The DPV oxidation peaks of UA and GU were found to be strongest at around 304 and 673 mV, respectively, against Ag/AgCl reference electrode, and this are well separated for effective simultaneous determination. UA and GU can be simultaneously determined by this method. Response is linear within the range 0.1-500 µM and 0.1-40 µM for UA and GU, respectively. The detection limits are 70 nM for UA and 50 nM for GU (at an S/N  ratio of 3). The TiO2-600/GP electrode showed excellent analytical performance when analyzing spiked urine and serum samples. Graphical abstract A graphical representation of cubic TiO2 nanoparticle formation during hydrolysis through sol-gel process.

Pt decorated MoS2 nanoflakes for ultrasensitive resistive humidity sensor.

In this work, we report the fabrication of a low power, humidity sensor where platinum nanoparticles (NPs) decorated few-layered molybdenum disulphide (MoS2) nanoflakes have been used as the sensing layer. A mixed solvent was used to exfoliate the nanoflakes from the bulk powder. Then the Pt/MoS2 composites were prepared by reducing Pt NPs from chloroplatinic acid hexahydrate using a novel reduction technique using sulphide salt. The successful reduction and composite preparation were confirmed using various material characterization tools like scanning electron microscopy, atomic force microscopy, transmission electron microscopy, x-ray diffraction, x-ray photoelectron spectroscopy, Raman spectroscopy and UV-visible spectroscopy. The humidity sensors were prepared by drop-coating the Pt-decorated MoS2 on gold interdigitated electrodes and then exposed to various levels of relative humidity (RH). Composites with different weight ratios of Pt were tested and the best response was shown by the Pt/MoS2 (0.25:1) sample with a record high response of ∼4000 times at 85% RH. The response and recovery times were ∼92 s and ∼154 s respectively with repeatable behaviour. The sensor performance was found to be stable when tested over a few months. The underlying sensing mechanisms along with detailed characterization of the various composites have been discussed.

An in-vivo study for targeted delivery of copper-organic complex to breast cancer using chitosan polymer nanoparticles.

We have developed a strategy for targeted delivery of metal-diketo complex, "bis(2,4-pentanedionato) copper(II)" to breast cancer cells both in-vitro and in-vivo. This metal-organic complex induced ROS and subsequently DNA damage as well as mitochondrial membrane depolarization was observed. The mitochondria rupture further triggered apoptosis. For in-vitro targeting strategies, two different approaches were employed, folic acid or her-2 specific peptide (KCCYSL) was attached to stearic acid-modified polymeric Chitosan nanoparticles loaded with metal-organic complex "bis(2,4-pentanedionato)copper(II)". This was tested on two pairs of isogenic cells (FR+/FR- MCf-7 and her2+ /her2- MCF-7) and it was observed that cells expressing the receptor were susceptible to the drug whereas non-expressing isogenic cells were almost un-affected. During in-vivo studies, mice receiving targeted delivery of bis(2,4-pentanedionato) copper (II) had increased survivability and reduced tumor volume compared to non-targeted drug delivery. During toxicity studies for liver enzymes it was also found that the mice receiving targeted drug did not show any sign of liver damage as well as other histology changes.

Metal based nanoparticles as cancer antigen delivery vehicles for macrophage based antitumor vaccine.

In the present study, we would like to evaluate the efficacy of modified metal oxide nanoparticles (NPs) as cancer antigen delivery vehicles for macrophage (MФs) based antitumor vaccine. The cobalt oxide nanoparticles (CoO NPs) were promising tools for delivery of antigens to antigen presenting cells and have induced an antitumor immune response. Synthesized CoO NPs were modified by N-phosphonomethyliminodiacetic acid (PMIDA), facilitated the conjugation of lysate antigen, i.e. cancer antigen derived from lysis of cancer cells. The cancer cell lysate antigen conjugated PMIDA-CoO NPs (Ag-PMIDA-CoO NPs) successfully activated macrophage (MФ) evident by the increasing the serum IFN-γ and TNF-α level. Immunization of mice with the Ag-PMIDA-CoO NPs constructed an efficient immunological adjuvant induced anticancer IgG responses, and increased the antibody dependent cellular cytotoxicity (ADCC) response than only lysate antigen treated group to combat the cancer cell. The nanocomplexes enhanced the anticancer CD4(+)T cell response in mice. The result showed that Ag-PMIDA-CoO NPs can stimulate the immune responses over only lysate antigens, which are the most important findings in this study. These NP-mediated Ag deliveries may significantly improve the anticancer immune response by activating MФs and may act as adjuvant and will balance the pro-inflammatory and anti-inflammatory immunoresponse. The crosstalk between the activated MФ with other immune competent cells will be monitored by measuring the cytokines which illustrate the total immunological network setups.

In vitro dose and duration dependent approaches for the assessment of ameliorative effects of nanoconjugated vancomycin against Staphylococcus aureus infection induced oxidative stress in murine peritoneal macrophages.

AIMS: The present study was aimed to evaluate the in vitro ameliorative effect of nanoconjugated vancomycin (NV) against vancomycin sensitive and resistant strains of Staphylococcus aureus infection-induced oxidative stress in murine peritoneal macrophage. METHODS: Peritoneal macrophages from mice were treated with VSSA and VRSA (5 × 10(6) CFU/mL), VSSA + NV (5-250 µg/ml) and VRSA + NV (5-250 µg/ml) for 18 h, having 3 h interval in culture media; and the superoxide anion generation, lipid peroxidation, protein oxidation, antioxidant enzymes status and glutathione enzymes activity were monitored. RESULTS: The significantly increased free radical generation, lipid peroxidation, protein carbonyls and oxidized glutathione levels were observed in VSSA and VRSA treated group as compared to control group; where as reduced glutathione level, antioxidant enzymes status and glutathione dependent enzymes were decreased significantly. All these changes come near to control in NV treated group in a dose and duration dependent fashion. Among the different doses and duration intervals of NV, maximum ameliorative effect was observed by 100 µg/ml for 12 h treatment which does not produce any damage to the cell. CONCLUSIONS: These findings suggest the potential use and beneficial role of nanoconjugated vancomycin as a modulator of S. aureus infection-induced cellular damage in murine peritoneal macrophage.

A simple synthesis of nitrogen doped porous graphitic carbon: Electrochemical determination of paracetamol in presence of ascorbic acid and p-aminophenol.

Graphite paste electrode modified with nitrogen doped porous carbon (NDPC) is used for the detections of paracetamol (PCM), ascorbic acid (AA) and p-aminophenol (PAP) at relatively low concentration. NDPC is synthesized by direct carbonization of Zn(OAc)2 incorporated melamine-formaldehyde resin microsphere. The NDPC shows small pore diameters centered at 3.14 nm and 8.12 nm and has a pseudo graphitic structure with reasonable porous matrix. The lower limit of detections (S/N = 3) for PCM, AA, and PAP are found to be 30 nM, 720 nM and 10 nM respectively. Under optimized experimental condition, the linear ranges of determination for PCM and AA are 1-400 µM, 10-2700 µM respectively in mixture. Similarly for PCM and PAP mixture, the linear ranges of determination are found to be 1-90 µM. It is also used for the analysis of urine and pharmaceutical products with better sensitivity.

Cobalt oxide nanoparticles induced oxidative stress linked to activation of TNF-α/caspase-8/p38-MAPK signaling in human leukemia cells.

The purpose of this study was to determine the intracellular signaling transduction pathways involved in oxidative stress induced by nanoparticles in cancer cells. Activation of reactive oxygen species (ROS) has some therapeutic benefits in arresting the growth of cancer cells. Cobalt oxide nanoparticles (CoO NPs) are an interesting compound for oxidative cancer therapy. Our results showed that CoO NPs elicited a significant (P <0.05) amount of ROS in cancer cells. Co-treatment with N-aceyltine cystine (an inhibitor of ROS) had a protective role in cancer cell death induced by CoO NPs. In cultured cells, the elevated level of tumor necrosis factor-alpha (TNF-α) was noted after CoO NPs treatment. This TNF-α persuaded activation of caspase-8 followed by phosphorylation of p38 mitogen-activated protein kinase and induced cell death. This study showed that CoO NPs induced oxidative stress and activated the signaling pathway of TNF-α-Caspase-8-p38-Caspase-3 to cancer cells.

A spatio-temporal cardiomyocyte targeted vector system for efficient delivery of therapeutic payloads to regress cardiac hypertrophy abating bystander effect.

Diverse array of therapeutic regimens, drugs or siRNA, are commonly used to regress cardiac hypertrophy, although, bystander effect and lower retention of bioactive molecules significantly reduce their functional clinical efficacy. Carvedilol, a widely used and effective anti-hypertrophic drug, simultaneously blocks ß-adrenergic receptors non-specifically in various organs. Likewise, non-specific genome-wide downregulation of p53 expression by specific siRNA efficiently abrogates cardiac hypertrophy but results in extensive tumorigenesis affecting bystander organs. Therefore, delivery of such therapeutics had been a challenge in treating cardiovascular dysfunction. Cardiac tissue engineering was successfully accomplished in this study, by encapsulating such bioactive molecules with a stearic acid modified Carboxymethyl chitosan (CMC) nanopolymer conjugated to a homing peptide for delivery to hypertrophied cardiomyocytes in vivo. The peptide precisely targeted cardiomyocytes while CMC served as the vector mediator to pathological myocardium. Controlled delivery of active therapeutic payloads within cardiomyocytes resulted in effective regression of cardiac hypertrophy. Thus, this novel nano-construct as a spatio-temporal vector would be a potential tool for developing effective therapeutic strategies within cardiac micro-environment via targeted knockdown of causal genes.

Phosphonomethyl iminodiacetic acid-conjugated cobalt oxide nanoparticles liberate Co(++) ion-induced stress associated activation of TNF-α/p38 MAPK/caspase 8-caspase 3 signaling in human leukemia cells.

The aim of this work is to understand the potential health effects of metal nanoparticles by exposing human leukemic cell lines (jurkat, K562 and KG1A cells) to nanosize phosphonomethyl iminodiacetic acid coated cobalt oxide (PMIDA-CoO) NPs. The synthesized PMIDA-CoO NPs were characterized by XRD, dynamic light scattering, transmission electron microscopy and scanning electron microscopy. Our results showed that exposure of leukemic cell lines to PMIDA-CoO NPs caused reactive oxygen species (ROS) generation by increasing the concentration of free Co(++) ions in cancer microenvironment. But at physiological pH, PMIDA-CoO liberates little amount of Co(++) ions into media and exerts lower toxicity to normal cells up to a certain dose. PMIDA-CoO NPs caused DNA damage in leukemic cell lines, which was reflected by an increase in apoptosis of jurkat, KG-1A and K562 cells. PMIDA-CoO NPs induced apoptosis by increasing pro-inflammatory cytokines, primarily TNF-α. The in vivo study shows that PMIDA-CoO NPs were efficiently killed DLA cells. These findings have important implications for understanding the potential anticancer property induced by surface-modified cobalt oxide nanoparticles.

Toxicity of cobalt oxide nanoparticles to normal cells; an in vitro and in vivo study.

The aim of this study was to find out the intracellular signaling transduction pathways involved in cobalt oxide nanoparticles (CoO NPs) mediated oxidative stress in vitro and in vivo system. Cobalt oxide nanoparticles released excess Co++ ions which could activated the NADPH oxidase and helps in generating the reactive oxygen species (ROS). Our results showed that CoO NPs elicited a significant (p<0.05) amount of ROS in lymphocytes. In vitro pretreatment with N-acetylene cystine had a protective role on lymphocytes death induced by CoO NPs. In vitro and in vivo results showed the elevated level of TNF-α after CoO NPs treatment. This TNF-α phosphorylated the p38 mitogen-activated protein kinase followed by activation of caspase 8 and caspase 3 which could induce cell death. This study showed that CoO NPs induced oxidative stress and activated the signaling pathway of TNF-α-caspase-8-p38-caspase-3 to primary immune cells. This study suggested that bare CoO NPs are a toxic for primary human immune cells that deals directly with human health. Surface modification or surface functionalization may open the gateway for further use of CoO NPs in different industrial use or in biomedical sciences.

Biocompatible mesoporous silica-coated superparamagnetic manganese ferrite nanoparticles for targeted drug delivery and MR imaging applications.

Multifunctional mesoporous silica-coated superparamagnetic manganese ferrite (MnFe2O4) nanoparticles (M-MSN) were synthesized and evaluated for targeted drug delivery and magnetic resonance imaging (MRI) applications. MnFe2O4 nanoparticles were prepared by solvothermal route and were silica-coated by surface silylation using sol-gel reactions. Subsequently, silylation was done using (3-aminopropyl)triethoxysilane in presence of a surfactant (CTAB), followed by selective etching of the surfactant molecules that resulted in amine-functionalized superparamagnetic nanoparticles (NH2-MSN). Further modification of the surface of the NH2-MSN with targeting (folate) or fluorescent (RITC) molecules resulted in M-MSN. The formation of the M-MSN was proved by several characterization techniques viz. XRD, XPS, HRTEM, FESEM, VSM, BET surface area measurement, FTIR, and UV-Vis spectroscopy. The M-MSN were loaded with anticancer drug Doxorubicin and the efficacy of the DOX loaded M-MSN was evaluated through in vitro cytotoxicity, fluorescence microscopy, and apoptosis studies. The in vivo biocompatibility of the M-MSN was demonstrated in a mice-model system. Moreover, the M-MSN also acted as superior MRI contrast agent owing to a high magnetization value as well as superparamagnetic behavior at room temperature. These folate-conjugated nanoparticles (FA-MSN) exhibited stronger T2-weighted MRI contrast towards HeLa cells as compared to the nanoparticles without folate conjugation, justifying their potential importance in MRI based diagnosis of cancer. Such M-MSN with a magnetic core required for MRI imaging, a porous shell for carrying drug molecules, a targeting moeity for cancer cell specificity and a fluorescent molecule for imaging, all integrated into a single system, may potentially serve as an excellent material in biomedical applications.

High throughput electron transfer from carbon dots to chloroplast: a rationale of enhanced photosynthesis.

A biocompatible amine functionalized fluorescent carbon dots were developed and isolated for gram scale applications. Such carbogenic quantum dots can strongly conjugate over the surface of the chloroplast and due to that strong interaction the former can easily transfer electrons towards the latter by assistance of absorbed light or photons. An exceptionally high electron transfer from carbon dots to the chloroplast can directly effect the whole chain electron transfer pathway in a light reaction of photosynthesis, where electron carriers play an important role in modulating the system. As a result, carbon dots can promote photosynthesis by modulating the electron transfer process as they are capable of fastening the conversion of light energy to the electrical energy and finally to the chemical energy as assimilatory power (ATP and NADPH).

Chitosan-modified cobalt oxide nanoparticles stimulate TNF-α-mediated apoptosis in human leukemic cells.

The objective of this study was to develop chitosan-based delivery of cobalt oxide nanoparticles to human leukemic cells and investigate their specific induction of apoptosis. The physicochemical properties of the chitosan-coated cobalt oxide nanoparticles were characterized using transmission electron microscopy, dynamic light scattering, X-ray diffraction, and Fourier transform infrared spectroscopy. The solubility of chitosan-coated cobalt oxide nanoparticles was higher at acidic pH, which helps to release more cobalt ions into the medium. Chitosan-coated cobalt oxide nanoparticles showed good compatibility with normal cells. However, our results showed that exposure of leukemic cells (Jurkat cells) to chitosan-coated cobalt oxide nanoparticles caused an increase in reactive oxygen species generation that was abolished by pretreatment of cells with the reactive oxygen species scavenger N-acetyl-L-cysteine. The apoptosis of Jurkat cells was confirmed by flow-cytometric analysis. Induction of TNF-α secretion was observed from stimulation of Jurkat cells with chitosan-coated cobalt oxide nanoparticles. We also tested the role of TNF-α in the induction of Jurkat cell death in the presence of TNF-α and caspase inhibitors. Treatment of leukemic cells with a blocker had a greater effect on cancer cell viability. From our findings, oxidative stress and caspase activation are involved in cancer cell death induced by chitosan-coated cobalt oxide nanoparticles.

Interplay between autophagy and apoptosis mediated by copper oxide nanoparticles in human breast cancer cells MCF7.

BACKGROUND: Metal oxide nanoparticles are well known to generate oxidative stress and deregulate normal cellular activities. Among these, transition metals copper oxide nanoparticles (CuO NPs) are more compelling than others and able to modulate different cellular responses. METHODS: In this work, we have synthesized and characterized CuO NPs by various biophysical methods. These CuO NPs (~30nm) induce autophagy in human breast cancer cell line, MCF7 in a time- and dose-dependent manner. Cellular autophagy was tested by MDC staining, induction of green fluorescent protein-light chain 3 (GFP-LC3B) foci by confocal microscopy, transfection of pBABE-puro mCherry-EGFP-LC3B plasmid and Western blotting of autophagy marker proteins LC3B, beclin1 and ATG5. Further, inhibition of autophagy by 3-MA decreased LD50 doses of CuO NPs. Such cell death was associated with the induction of apoptosis as revealed by FACS analysis, cleavage of PARP, de-phosphorylation of Bad and increased cleavage product of caspase 3. siRNA mediated inhibition of autophagy related gene beclin1 also demonstrated similar results. Finally induction of apoptosis by 3-MA in CuO NP treated cells was observed by TEM. RESULTS: This study indicates that CuO NPs are a potent inducer of autophagy which may be a cellular defense against the CuO NP mediated toxicity and inhibition of autophagy switches the cellular response into apoptosis. CONCLUSIONS: A combination of CuO NPs with the autophagy inhibitor is essential to induce apoptosis in breast cancer cells. GENERAL SIGNIFICANCE: CuO NP induced autophagy is a survival strategy of MCF7 cells and inhibition of autophagy renders cellular fate to apoptosis.