Nitrogen-doped multi-walled carbon nanotubes (ND-MWCNTs) are modified multi-walled carbon nanotubes (MWCNTs) with enhanced electrical properties that are used in a variety of applications, including fuel cells and sensors; however, the mode of toxic action of ND-MWCNT has yet to be fully elucidated. In the present study, we compared the interaction of ND-MWCNT or pristine MWCNT-7 with human small airway epithelial cells (SAEC) and evaluated their subsequent bioactive effects. Transmission electron microscopy, X-ray photoelectron spectroscopy, Raman spectroscopy, and X-ray diffraction suggested the presence of N-containing defects in the lattice of the nanotube. The ND-MWCNTs were determined to be 93.3% carbon, 3.8% oxygen, and 2.9% nitrogen. A dose–response cell proliferation assay showed that low doses of ND-MWCNT (1.2 mg/ml) or MWCNT-7 (0.1 mg/ml) increased cellular proliferation, while the highest dose of 120 mg/ml of either material decreased proliferation. ND-MWCNT and MWCNT-7 appeared to interact with SAEC at 6 h and were internalized by 24 h. ROS were elevated at 6 and 24 h in ND-MWCNT exposed cells, but only at 6 h in MWCNT-7 exposed cells. Significant alterations to the cell cycle were observed in SAEC exposed to either 1.2 mg/ml of ND-MWCNT or MWCNT-7 in a time and material-dependent manner, possibly suggesting potential damage or alterations to cell cycle machinery. Our results indicate that ND-MWCNT induce effects in SAEC over a time and dose-related manner which differ from MWCNT-7. Therefore, the physicochemical characteristics of the materials appear to alter their biological effects.

BackgroundAlthough classified as metal oxides, cobalt monoxide (CoO) and lanthanum oxide (La2O3) nanoparticles, as representative transition and rare earth oxides, exhibit distinct material properties that may result in different hazardous potential in the lung. The current study was undertaken to compare the pulmonary effects of aerosolized whole body inhalation of these nanoparticles in mice.ResultsMice were exposed to filtered air (control) and 10 or 30 mg/m3 of each particle type for 4 days and then examined at 1 h, 1, 7 and 56 days post-exposure. The whole lung burden 1 h after the 4 day inhalation of CoO nanoparticles was 25 % of that for La2O3 nanoparticles. At 56 days post exposure, < 1 % of CoO nanoparticles remained in the lungs; however, 22–50 % of the La2O3 nanoparticles lung burden 1 h post exposure was retained at 56 days post exposure for low and high exposures. Significant accumulation of La2O3 nanoparticles in the tracheobronchial lymph nodes was noted at 56 days post exposure. When exposed to phagolysosomal simulated fluid, La nanoparticles formed urchin-shaped LaPO4 structures, suggesting that retention of this rare earth oxide nanoparticle may be due to complexation of cellular phosphates within lysosomes. CoO nanoparticles caused greater lactate dehydrogenase release in the bronchoalveolar fluid (BALF) compared to La2O3 nanoparticles at 1 day post exposure, while BAL cell differentials indicate that La2O3 nanoparticles generated more inflammatory cell infiltration at all doses and exposure points. Histopathological analysis showed acute inflammatory changes at 1 day after inhalation of either CoO or La2O3 nanoparticles. Only the 30 mg/m3 La2O3 nanoparticles exposure caused chronic inflammatory changes and minimal fibrosis at day 56 post exposure. This is in agreement with activation of the NRLP3 inflammasome after in vitro exposure of differentiated THP-1 macrophages to La2O3 but not after CoO nanoparticles exposure.ConclusionTaken together, the inhalation studies confirmed the trend of our previous sub-acute aspiration study, which reported that CoO nanoparticles induced more acute pulmonary toxicity, while La2O3 nanoparticles caused chronic inflammatory changes and minimal fibrosis.Electronic supplementary materialThe online version of this article (doi:10.1186/s12989-016-0155-3) contains supplementary material, which is available to authorized users.

Cobalt monoxide (CoO) and lanthanum oxide (La2O3) nanoparticles are 2 metal oxide nanoparticles with different redox potentials according to their semiconductor properties. By utilizing these two nanoparticles, this study sought to determine how metal oxide nanoparticle’s mode of toxicological action is related to their physio-chemical properties in human small airway epithelial cells (SAEC). We investigated cellular toxicity, production of superoxide radicals and alterations in gene expression related to oxidative stress, and cellular death at 6 and 24 h following exposure to CoO and La2O3 (administered doses: 0, 5, 25, and 50 μg/ml) nanoparticles. CoO nanoparticles induced gene expression related to oxidative stress at 6 h. After characterizing the nanoparticles, transmission electron microscope analysis showed SAEC engulfed CoO and La2O3 nanoparticles. CoO nanoparticles were toxic after 6 and 24 h of exposure to 25.0 and 50.0 μg/ml administered doses, whereas, La2O3 nanoparticles were toxic only after 24 h using the same administered doses. Based upon the Volumetric Centrifugation Method in vivo Sedimentation, Diffusion, and Dosimetry, the dose of CoO and La2O3 nanoparticles delivered at 6 and 24 h were determined to be: CoO: 1.25, 6.25, and 12.5 μg/ml; La2O3: 5, 25, and 50 μg/ml and CoO: 4, 20, and 40 μg/ml; and La2O3: 5, 25, 50 μg/ml, respectively. CoO nanoparticles produced more superoxide radicals and caused greater stimulation of total tyrosine and threonine phosphorylation at both 6 and 24 h when compared with La2O3 nanoparticles. Taken together, these data provide evidence that different toxicological modes of action were involved in CoO and La2O3 metal oxide nanoparticle-induced cellular toxicity.

No abstract

Effects of Nitrogen-Doped and Pristine Multi-Walled Carbon Nanotubes in Human Lung Cells Amy Mihalchik Multi-Walled Carbon Nanotubes (MWCNT) were first described by Iijima in 1991 as "needle-like tubes" made up of concentric sheets of graphene lattice composed of hexagonal carbon units. MWCNT have been reported to be extremely strong, lightweight , and durable, thus making them a highly valued nanomaterial commercially. In order to improve their electrical conductivity and dispersibility for industrial and biomedical uses, materials scientists began functionalizing CNT in the mid-1990s. One type of functionalized MWCNT, nitrogen doped-MWCNT (ND-MWCNT), have nitrogen directly incorporated into the carbon lattice, disrupting sp 2 bonding and decreasing the crystallinity of MWCNT. Nitrogen-doping significantly increases the brittleness, chemical reactivity, and n-type semiconductor activity of this material, and may also have interesting implications for its bioactivity. Alterations in physicochemical properties such as size, surface reactivity, agglomeration, and charge have been suggested to significantly impact the overall toxicity of MWCNT, but less in known on the effects of MWCNT functionalization. While the unique physicochemical properties of these materials generate exciting new possibilities for industrial and consumer products, the potential for unintended human exposure, especially and primarily through inhalation, has been of concern. Numerous animal studies have shown that MWCNT induce inflammation and pulmonary fibrosis at occupationally relevant exposure doses, but have yet to provide detailed information on the occupational risk of ND-MWCNT and other functionalized MWCNT. In recent years, the U.S. Environmental Protection Agency and National Toxicology Program have called for increased use and validation of predictive in vitro models to lessen the need for costly and time-consuming in vivo projects to determine general toxicity of nanomaterials. The studies presented here focused on developing and utilizing various in vitro models employing human Small Airway Epithelial Cells (SAEC), human bronchial epithelial cells (BEAS-2B), and normal human lung fibroblasts (WI-38) to study the bioactivities of ND-MWCNT and pristine Mitsui-7 MWCNT (MWCNT-7). However, it was found that the type of in vitro system utilized as well as the nanomaterial dosing schema could have serious and significant impact on the results and their subsequent interpretation and relevance to real-world exposures. Here, we provide an assessment of results on the inflammatory and fibrotic potential of ND-MWCNT and MWCNT-7 and the in vitro approaches we used to address these aims including monoculture and conditioned media, as well as concentration-based and surface area-based dosing. Results suggested that ND-MWCNT and MWCNT-7 induced an acute particle and dose-dependent inflammatory response in SAEC and BEAS-2B, suggesting that the physicochemical properties of these materials may impact their bioactivity. WI-38 directly exposed to ND-...