Engineered Graphene Oxide Nanocomposite Capable of Preventing the Evolution of Antimicrobial Resistance.

Antimicrobial resistance (AMR) is spreading worldwide and keeps evolving to adapt to antibiotics, causing increasing threats in clinics, which necessitates the exploration of antimicrobial agents for not only killing of resistant cells but also prevention of AMR progression. However, so far, there has been no effective approach. Herein, we designed lanthanum hydroxide and graphene oxide nanocomposites (La@GO) to confer a synergistic bactericidal effect in all tested resistant strains. More importantly, long-term exposure of E. coli (AMR) to subminimum inhibitory concentrations of La@GO does not trigger detectable secondary resistance, while conventional antibiotics and silver nanoparticles lead to a 16- to 64-fold increase in tolerance. The inability of E. coli to evolve resistance to La@GO is likely due to a distinctive extracellular multitarget invasion killing mechanism involving lipid dephosphorylation, lipid peroxidation, and peptidoglycan disruption. Overall, our results highlight La@GO nanocomposites as a promising solution to combating resistant bacteria without inducing the evolution of AMR.

Multi-hierarchical profiling the structure-activity relationships of engineered nanomaterials at nano-bio interfaces.

Increasing concerns over the possible risks of nanotechnology necessitates breakthroughs in structure-activity relationship (SAR) analyses of engineered nanomaterials (ENMs) at nano-bio interfaces. However, current nano-SARs are often based on univariate assessments and fail to provide tiered views on ENM-induced bio-effects. Here we report a multi-hierarchical nano-SAR assessment for a representative ENM, Fe2O3, by metabolomics and proteomics analyses. The established nano-SAR profile allows the visualizing of the contributions of seven basic properties of Fe2O3 to its diverse bio-effects. For instance, although surface reactivity is responsible for Fe2O3-induced cell migration, the inflammatory effects of Fe2O3 are determined by aspect ratio (nanorods) or surface reactivity (nanoplates). These nano-SARs are examined in THP-1 cells and animal lungs, which allow us to decipher the detailed mechanisms including NLRP3 inflammasome pathway and monocyte chemoattractant protein-1-dependent signaling. This study provides more insights for nano-SARs, and may facilitate the tailored design of ENMs to render them desired bio-effects.

Design and Synthesis of Waterborne Polyurethanes.

Waterborne polyurethanes (WBPUs) have attracted increasing attention in a wide range of industrial applications because of their versatile properties as well as ecofriendly nature. Although extensive research has been carried out on WBPU synthesis, the roles of some of the key synthesis components remain unclear. In this study, through systematically controlling and fine tuning the precursor compositions and reaction conditions, over 300 WBPUs are synthesized. This research enables the roles of several key components that govern WBPU physicochemical properties and ultimately the potential WBPU applications to be identified. Using hair styling as an example, it is demonstrated that only the WBPUs with an optimal range of properties (e.g., Young's modulus >150 MPa, elongation at break: 15-300%, moisture uptake <10%) can achieve strong styling performance. To further improve the natural-feel sensory benefits in the final styling products, a number of fatty acids with different carbon chain lengths or unsaturation levels are incorporated into WBPUs. Among the ten fatty acids studied, linoleic acid is identified as the most preferred additive. Both in vitro and in vivo testing demonstrate that WBPUs with optimal properties are promising materials for developing strong, long-lasting styling products with natural feel.

Surface Oxidation of Graphene Oxide Determines Membrane Damage, Lipid Peroxidation, and Cytotoxicity in Macrophages in a Pulmonary Toxicity Model.

While two-dimensional graphene oxide (GO) is used increasingly in biomedical applications, there is uncertainty on how specific physicochemical properties relate to biocompatibility in mammalian systems. Although properties such as lateral size and the colloidal properties of the nanosheets are important, the specific material properties that we address here is the oxidation state and reactive surface groups on the planar surface. In this study, we used a GO library, comprising pristine, reduced (rGO), and hydrated GO (hGO), in which quantitative assessment of the hydroxyl, carboxyl, epoxy, and carbon radical contents was used to study the impact on epithelial cells and macrophages, as well as in the murine lung. Strikingly, we observed that hGO, which exhibits the highest carbon radical density, was responsible for the generation of cell death in THP-1 and BEAS-2B cells as a consequence of lipid peroxidation of the surface membrane, membrane lysis, and cell death. In contrast, pristine GO had lesser effects, while rGO showed extensive cellular uptake with minimal effects on viability. In order to see how these in vitro effects relate to adverse outcomes in the lung, mice were exposed to GOs by oropharyngeal aspiration. Animal sacrifice after 40 h demonstrated that hGO was more prone than other materials to generate acute lung inflammation, accompanied by the highest lipid peroxidation in alveolar macrophages, cytokine production (LIX, MCP-1), and LDH release in bronchoalveolar lavage fluid. Pristine GO showed less toxicity, whereas rGO had minimal effects. We demonstrate that the surface oxidation state and carbon radical content play major roles in the induction of toxicity by GO in mammalian cells and the lung.

Enhanced Immune Adjuvant Activity of Aluminum Oxyhydroxide Nanorods through Cationic Surface Functionalization.

Aluminum-salt-based vaccine adjuvants are prevailingly used in FDA-approved vaccines for the prevention of infectious diseases for over eighty years. Despite their safe applications, the mechanisms regarding how the material characteristics affect the interactions at nano-bio interface and immunogenicity remain unclear. Recently, studies have indicated that the activation of NLRP3 inflammasome plays a critical role in inducing adjuvant effects that are controlled by the inherent shape and hydroxyl contents of aluminum oxyhydroxide (AlOOH) nanoparticles; however, the detailed relationship between surface properties and adjuvant effects for these materials remains unknown. Thus, we engineered AlOOH nanorods (ALNRs) with controlled surface functionalization and charge to assess their effects on the activation of NLRP3 inflammasome in vitro and the potentiation of immunogenicity in vivo. It is demonstrated that NH2-functionalized ALNRs exhibited higher levels of cellular uptake, lysosomal damage, oxidative stress, and NLRP3 inflammasome activation than pristine and SO3H-functionalized ALNRs in cells. This structure-activity relationship also correlates with the adjuvant activity of the material using ovalbumin (OVA) in a mouse vaccination model. This study demonstrates that surface functionalization of ALNRs is critical for rational design of aluminum-based adjuvants to boost antigen-specific immune responses for more effective and long-lasting vaccination.

Agglomeration Determines Effects of Carbonaceous Nanomaterials on Soybean Nodulation, Dinitrogen Fixation Potential, and Growth in Soil.

The potential effects of carbonaceous nanomaterials (CNMs) on agricultural plants are of concern. However, little research has been performed using plants cultivated to maturity in soils contaminated with various CNMs at different concentrations. Here, we grew soybean for 39 days to seed production in soil amended with 0.1, 100, or 1000 mg kg-1 of either multiwalled carbon nanotubes (MWCNTs), graphene nanoplatelets (GNPs), or carbon black (CB) and studied plant growth, nodulation, and dinitrogen (N2) fixation potential. Plants in all CNM treatments flowered earlier (producing 60% to 372% more flowers when reproduction started) than the unamended controls. The low MWCNT-treated plants were shorter (by 15%) with slower leaf cover expansion (by 26%) and less final leaf area (by 24%) than the controls. Nodulation and N2 fixation potential appeared negatively impacted by CNMs, with stronger effects at lower CNM concentrations. All CNM treatments reduced the whole-plant N2 fixation potential, with the highest reductions (by over 91%) in the low and medium CB and the low MWCNT treatments. CB and GNPs appeared to accumulate inside nodules as observed by transmission electron microscopy. CNM dispersal in aqueous soil extracts was studied to explain the inverse dose-response relationships, showing that CNMs at higher concentrations were more agglomerated (over 90% CNMs settled as agglomerates >3 µm after 12 h) and therefore proportionally less bioavailable. Overall, our findings suggest that lower concentrations of CNMs in soils could be more impactful to leguminous N2 fixation, owing to greater CNM dispersal and therefore increased bioavailability at lower concentrations.

Reduction of pulmonary toxicity of metal oxide nanoparticles by phosphonate-based surface passivation.

BACKGROUND: The wide application of engineered nanoparticles has induced increasing exposure to humans and environment, which led to substantial concerns on their biosafety. Some metal oxides (MOx) have shown severe toxicity in cells and animals, thus safe designs of MOx with reduced hazard potential are desired. Currently, there is a lack of a simple yet effective safe design approach for the toxic MOx. In this study, we determined the key physicochemical properties of MOx that lead to cytotoxicity and explored a safe design approach for toxic MOx by modifying their hazard properties. RESULTS: THP-1 and BEAS-2B cells were exposed to 0-200 µg/mL MOx for 24 h, we found some toxic MOx including CoO, CuO, Ni2O3 and Co3O4, could induce reactive oxygen species (ROS) generation and cell death due to the toxic ion shedding and/or oxidative stress generation from the active surface of MOx internalized into lysosomes. We thus hypothesized that surface passivation could reduce or eliminate the toxicity of MOx. We experimented with a series of surface coating molecules and discovered that ethylenediamine tetra (methylene phosphonic acid) (EDTMP) could form stable hexadentate coordination with MOx. The coating layer can effectively reduce the surface activity of MOx with 85-99% decrease of oxidative potential, and 65-98% decrease of ion shedding. The EDTMP coated MOx show negligible ROS generation and cell death in THP-1 and BEAS-2B cells. The protective effect of EDTMP coating was further validated in mouse lungs exposed to 2 mg/kg MOx by oropharyngeal aspiration. After 40 h exposure, EDTMP coated MOx show significant decreases of neutrophil counts, lactate dehydrogenase (LDH) release, MCP-1, LIX and IL-6 in bronchoalveolar lavage fluid (BALF), compared to uncoated particles. The haematoxylin and eosin (H&E) staining results of lung tissue also show EDTMP coating could significantly reduce the pulmonary inflammation of MOx. CONCLUSIONS: The surface reactivity of MOx including ion shedding and oxidative potential is the dominated physicochemical property that is responsible for the cytotoxicity induced by MOx. EDTMP coating could passivate the surface of MOx, reduce their cytotoxicity and pulmonary hazard effects. This coating would be an effective safe design approach for a broad spectrum of toxic MOx, which will facilitate the safe use of MOx in commercial nanoproducts.

Comparison of the effects of commercial coated and uncoated ZnO nanomaterials and Zn compounds in kidney bean (Phaseolus vulgaris) plants.

Bean (Phaseolus vulgaris) plants were grown for 45 days in soil amended with either uncoated (Z-COTE®) and coated (Z-COTE HP1®) ZnO nanomaterials (NMs), bulk ZnO and ZnCl2, at 0-500mg/kg. At harvest, growth parameters, chlorophyll, and essential elements were determined. None of the treatments affected germination and pod production, and only ZnCl2 at 250 and 500mg/kg reduced relative chlorophyll content by 34% and 46%, respectively. While Z-COTE® did not produce phenotypic changes, Z-COTE HP1®, at all concentrations, increased root length (∼44%) and leaf length (∼13%) compared with control. Bulk ZnO reduced root length (53%) at 62.5mg/kg and ZnCl2 reduced leaf length (16%) at 125mg/kg. Z-COTE®, at 125mg/kg, increased Zn by 203%, 139%, and 76% in nodules, stems, and leaves, respectively; while at the same concentration, Z-COTE HP1® increased Zn by 89%, 97%, and 103% in roots, stems, and leaves, respectively. At 125mg/kg, Z-COTE HP1® increased root S (65%) and Mg (65%), while Z-COTE® increased stem B (122%) and Mn (73%). Bulk ZnO and ZnCl2 imposed more toxicity to kidney bean than the NMs, since they reduced root and leaf elongation, respectively, and the concentration of several essential elements in tissues.

Pro-Inflammatory and Pro-Fibrogenic Effects of Ionic and Particulate Arsenide and Indium-Containing Semiconductor Materials in the Murine Lung.

We have recently shown that the toxicological potential of GaAs and InAs particulates in cells is size- and dissolution-dependent, tending to be more pronounced for nano- vs micron-sized particles. Whether the size-dependent dissolution and shedding of ionic III-V materials also apply to pulmonary exposure is unclear. While it has been demonstrated that micron-sized III-V particles, such as GaAs and InAs, are capable of inducing hazardous pulmonary effects in an occupational setting as well as in animal studies, the effect of submicron particles (e.g., the removal of asperities during processing of semiconductor wafers) is unclear. We used cytokine profiling to compare the pro-inflammatory effects of micron- and nanoscale GaAs and InAs particulates in cells as well as the murine lung 40 h and 21 days after oropharyngeal aspiration. Use of cytokine array technology in macrophage and epithelial cell cultures demonstrated a proportionally higher increase in the levels of matrix metalloproteinase inducer (EMMPRIN), macrophage migration inhibitory factor (MIF), and interleukin 1ß (IL-1ß) by nanosized (n) GaAs and n-InAs as well as As(III). n-GaAs and n-InAs also triggered higher neutrophil counts in the bronchoalveolar lavage fluid (BALF) of mice than micronscale particles 40 h post-aspiration, along with increased production of EMMPRIN and MIF. In contrast, in animals sacrificed 21 days after exposure, only n-InAs induced fibrotic lung changes as determined by increased lung collagen as well as increased levels of TGF-ß1 and PDGF-AA in the BALF. A similar trend was seen for EMMPRIN and matrix metallopeptidase (MMP-9) levels in the BALF. Nano- and micron-GaAs had negligible subacute effects. Importantly, the difference between the 40 h and 21 days data appears to be biopersistence of n-InAs, as demonstrated by ICP-OES analysis of lung tissue. Interestingly, an ionic form of In, InCl3, also showed pro-fibrogenic effects due to the formation of insoluble In(OH)3 nanostructures. All considered, these data indicate that while nanoscale particles exhibit increased pro-inflammatory effects in the lung, most effects are transient, except for n-InAs and insoluble InCl3 species that are biopersistent and trigger pro-fibrotic effects. These results are of potential importance for the understanding the occupational health effects of III-V particulates.

Surface coating changes the physiological and biochemical impacts of nano-TiO2 in basil (Ocimum basilicum) plants.

Little is known about the effects of surface coating on the interaction of engineered nanoparticles (ENPs) with plants. In this study, basil (Ocimum basilicum) was cultivated for 65 days in soil amended with unmodified, hydrophobic (coated with aluminum oxide and dimethicone), and hydrophilic (coated with aluminum oxide and glycerol) titanium dioxide nanoparticles (nano-TiO2) at 125, 250, 500, and 750 mg nano-TiO2 kg-1 soil. ICP-OES/MS, SPAD meter, and UV/Vis spectrometry were used to determine Ti and essential elements in tissues, relative chlorophyll content, carbohydrates, and antioxidant response, respectively. Compared with control, hydrophobic and hydrophilic nano-TiO2 significantly reduced seed germination by 41% and 59%, respectively, while unmodified and hydrophobic nano-TiO2 significantly decreased shoot biomass by 31% and 37%, respectively (p ≤ 0.05). Roots exposed to hydrophobic particles at 750 mg kg-1 had 87% and 40% more Ti than the pristine and hydrophilic nano-TiO2; however, no differences were found in shoots. The three types of particles affected the homeostasis of essential elements: at 500 mg kg-1, unmodified particles increased Cu (104%) and Fe (90%); hydrophilic increased Fe (90%); while hydrophobic increased Mn (339%) but reduced Ca (71%), Cu (58%), and P (40%). However, only hydrophobic particles significantly reduced root elongation by 53%. Unmodified, hydrophobic, and hydrophilic particles significantly reduced total sugar by 39%, 38%, and 66%, respectively, compared with control. Moreover, unmodified particles significantly decreased reducing sugar (34%), while hydrophobic particles significantly reduced starch (35%). Although the three particles affected basil plants, coated particles impacted the most its nutritional quality, since they altered more essential elements, starch, and reducing sugars.

Safe-by-Design CuO Nanoparticles via Fe-Doping, Cu-O Bond Length Variation, and Biological Assessment in Cells and Zebrafish Embryos.

The safe implementation of nanotechnology requires nanomaterial hazard assessment in accordance with the material physicochemical properties that trigger the injury response at the nano/bio interface. Since CuO nanoparticles (NPs) are widely used industrially and their dissolution properties play a major role in hazard potential, we hypothesized that tighter bonding of Cu to Fe by particle doping could constitute a safer-by-design approach through decreased dissolution. Accordingly, we designed a combinatorial library in which CuO was doped with 1-10% Fe in a flame spray pyrolysis reactor. The morphology and structural properties were determined by XRD, BET, Raman spectroscopy, HRTEM, EFTEM, and EELS, which demonstrated a significant reduction in the apical Cu-O bond length while simultaneously increasing the planar bond length (Jahn-Teller distortion). Hazard screening was performed in tissue culture cell lines and zebrafish embryos to discern the change in the hazardous effects of doped vs nondoped particles. This demonstrated that with increased levels of doping there was a progressive decrease in cytotoxicity in BEAS-2B and THP-1 cells, as well as an incremental decrease in the rate of hatching interference in zebrafish embryos. The dissolution profiles were determined and the surface reactions taking place in Holtfreter's solution were validated using cyclic voltammetry measurements to demonstrate that the Cu+/Cu2+ and Fe2+/Fe3+ redox species play a major role in the dissolution process of pure and Fe-doped CuO. Altogether, a safe-by-design strategy was implemented for the toxic CuO particles via Fe doping and has been demonstrated for their safe use in the environment.

Identification and Optimization of Carbon Radicals on Hydrated Graphene Oxide for Ubiquitous Antibacterial Coatings.

While the antibacterial properties of graphene oxide (GO) have been demonstrated across a spectrum of bacteria, the critical role of functional groups is unclear. To address this important issue, we utilized reduction and hydration methods to establish a GO library with different oxidation, hydroxyl, and carbon radical (•C) levels that can be used to study the impact on antibacterial activity. Using antibiotic-resistant bacteria as a test platform, we found that the •C density is most proximately associated with bacterial killing. Accordingly, hydrated GO (hGO), with the highest •C density, had the strongest antibacterial effects through membrane binding and induction of lipid peroxidation. To explore its potential applications, we demonstrated that coating of catheter and glass surfaces with hGO is capable of killing drug-resistant bacteria. In summary, •C is the principle surface moiety that can be utilized for clinical applications of GO-based antibacterial coatings.

Repetitive Dosing of Fumed Silica Leads to Profibrogenic Effects through Unique Structure-Activity Relationships and Biopersistence in the Lung.

Contrary to the notion that the use of fumed silica in consumer products can "generally (be) regarded as safe" (GRAS), the high surface reactivity of pyrogenic silica differs from other forms of synthetic amorphous silica (SAS), including the capacity to induce membrane damage and acute proinflammatory changes in the murine lung. In addition, the chain-like structure and reactive surface silanols also allow fumed silica to activate the NLRP3 inflammasome, leading to IL-1ß production. This pathway is known to be associated with subchronic inflammation and profibrogenic effects in the lung by α-quartz and carbon nanotubes. However, different from the latter materials, bolus dose instillation of 21 mg/kg fumed silica did not induce sustained IL-1ß production or subchronic pulmonary effects. In contrast, the NLRP3 inflammasome pathway was continuously activated by repetitive-dose administration of 3 × 7 mg/kg fumed silica, 1 week apart. We also found that while single-dose exposure failed to induce profibrotic effects in the lung, repetitive dosing can trigger increased collagen production, even at 3 × 3 mg/kg. The change between bolus and repetitive dosing was due to a change in lung clearance, with recurrent dosing leading to fumed silica biopersistence, sustained macrophage recruitment, and activation of the NLRP3 pathway. These subchronic proinflammatory effects disappeared when less surface-reactive titanium-doped fumed silica was used for recurrent administration. All considered, these data indicate that while fumed silica may be regarded as safe for some applications, we should reconsider the GRAS label during repetitive or chronic inhalation exposure conditions.

Differential pulmonary effects of CoO and La2O3 metal oxide nanoparticle responses during aerosolized inhalation in mice.

BACKGROUND: Although 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. RESULTS: Mice were exposed to filtered air (control) and 10 or 30 mg/m(3) 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/m(3) 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. CONCLUSION: Taken 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.

Multiwalled Carbon Nanotube Functionalization with High Molecular Weight Hyaluronan Significantly Reduces Pulmonary Injury.

Commercialization of multiwalled carbon nanotubes (MWCNT)-based applications has been hampered by concerns regarding their lung toxicity potential. Hyaluronic acid (HA) is a ubiquitously found polysaccharide, which is anti-inflammatory in its native high molecular weight form. HA-functionalized smart MWCNTs have shown promise as tumor-targeting drug delivery agents and can enhance bone repair and regeneration. However, it is unclear whether HA functionalization could reduce the pulmonary toxicity potential of MWCNTs. Using in vivo and in vitro approaches, we investigated the effectiveness of MWCNT functionalization with HA in increasing nanotube biocompatibility and reducing lung inflammatory and fibrotic effects. We utilized three-dimensional cultures of differentiated primary human bronchial epithelia to translate findings from rodent assays to humans. We found that HA functionalization increased stability and dispersion of MWCNTs and reduced postexposure lung inflammation, fibrosis, and mucus cell metaplasia compared with nonfunctionalized MWCNTs. Cocultures of fully differentiated bronchial epithelial cells (cultivated at air-liquid interface) and human lung fibroblasts (submerged) displayed significant reduction in injury, oxidative stress, as well as pro-inflammatory gene and protein expression after exposure to HA-functionalized MWCNTs compared with MWCNTs alone. In contrast, neither type of nanotubes stimulated cytokine production in primary human alveolar macrophages. In aggregate, our results demonstrate the effectiveness of HA functionalization as a safer design approach to eliminate MWCNT-induced lung injury and suggest that HA functionalization works by reducing MWCNT-induced epithelial injury.

Lanthanide Hydroxide Nanoparticles Induce Angiogenesis via ROS-Sensitive Signaling.

Recent studies suggest that the nanorods consisting of europium hydroxide could promote angiogenesis. In this study, it is sought to determine if additional types of nanoparticles are capable of enhancing angiogenesis and in addition, understand the underlying mechanisms. For this reason, a method is employed that combines a high throughput in vitro cell based screen coupled with an in vivo validation using vascular specific green fluorescent protein reporter transgenic zebrafish for examining proangiogenesis activity. After screening multiple types of nanoparticles, it is discovered that four of them, Eu(III) (OH)3 rods (Eu rods), Eu(III) (OH)3 spheres (Eu spheres), Tb(III) (OH)3 rods (Tb rods), and Tb(III) (OH)3 spheres (Tb spheres), are the most effective in promoting angiogenesis. It is also showed that ionic forms of europium nitrate [Eu(NO3 )3 ] (Eu) and terbium nitrate [Tb(NO3 )3 ] (Tb), the two lanthanide elements for these four nanoparticles, are also capable of enhancing angiogenesis. However, this effect is further enhanced by nanoparticle synthesis. Finally, it is demonstrated that reactive oxygen species H2 O2 is a key factor in the process of proangiogenesis by lanthanide elemental nanoparticles.

Toxicological Profiling of Highly Purified Metallic and Semiconducting Single-Walled Carbon Nanotubes in the Rodent Lung and E. coli.

The electronic properties of single-walled carbon nanotubes (SWCNTs) are potentially useful for electronics, optics, and sensing applications. Depending on the chirality and diameter, individual SWCNTs can be classified as semiconducting (S-SWCNT) or metallic (M-SWCNT). From a biological perspective, the hazard profiling of purified metallic versus semiconducting SWCNTs has been pursued only in bacteria, with the conclusion that aggregated M-SWCNTs are more damaging to bacterial membranes than S-SWCNTs. However, no comparative studies have been performed in a mammalian system, where most toxicity studies have been undertaken using relatively crude SWCNTs that include a M:S mix at 1:2 ratio. In order to compare the toxicological impact of SWCNTs sorted to enrich them for each of the chirality on pulmonary cells and the intact lung, we used density gradient ultracentrifugation and extensive rinsing to prepare S- and M-SWCNTs that are >98% purified. In vitro screening showed that both tube variants trigger similar amounts of interleukin 1ß (IL-1ß) and transforming growth factor (TGF-ß1) production in THP-1 and BEAS-2B cells, without cytotoxicity. Oropharyngeal aspiration confirmed that both SWCNT variants induce comparable fibrotic effects in the lung and abundance of IL-1ß and TGF-ß1 release in the bronchoalveolar lavage fluid. There was also no change in the morphology, membrane integrity, and viability of E. coli, in contradistinction to the previously published effects of aggregated tubes on the bacterial membrane. Collectively, these data indicate that the electronic properties and chirality do not independently impact SWCNT toxicological impact in the lung, which is of significance to the safety assessment and incremental use of purified tubes by industry.