10 research outputs found
Custom-Designed Nanomaterial Libraries for Testing Metal Oxide Toxicity
Advances in aerosol technology over the past 10 years have enabled the generation and design of ultrafine nanoscale materials for many applications. A key new method is flame spray pyrolysis (FSP), which produces particles by pyrolyzing a precursor solution in the gas phase. FSP is a highly versatile technique for fast, single-step, scalable synthesis of nanoscale materials. New innovations in particle synthesis using FSP technology, including variations in precursor chemistry, have enabled flexible, dry synthesis of loosely agglomerated, highly crystalline ultrafine powders (porosity ≥ 90%) of binary, ternary, and mixed-binary-and-ternary oxides. FSP can fulfill much of the increasing demand, especially in biological applications, for particles with specific material composition, high purity, and high crystallinity.In this Account, we describe a strategy for creating nanoparticle libraries (pure or Fedoped ZnO or TiO<sub>2</sub>) utilizing FSP and using these libraries to test hypotheses related to the particles’ toxicity. Our innovation lies in the overall integration of the knowledge we have developed in the last 5 years in (1) synthesizing nanomaterials to address specific hypotheses, (2) demonstrating the electronic properties that cause the material toxicity, (3) understanding the reaction mechanisms causing the toxicity, and (4) extracting from in vitro testing and in vivo testing in terrestrial and marine organisms the essential properties of safe nanomaterials.On the basis of this acquired knowledge, we further describe how the dissolved metal ion from these materials (Zn<sup>2+</sup> in this Account) can effectively bind with different cell constituents, causing toxicity. We use Fe–S protein clusters as an example of the complex chemical reactions taking place after free metal ions migrate into the cells.As a second example, TiO<sub>2</sub> is an active material in the UV range that exhibits photocatalytic behavior. The induction of electron–hole (e<sup>–</sup>/h<sup>+</sup>) pairs followed by free radical production is a key mechanism for biological injury. We show that decreasing the bandgap energy increases the phototoxicity in the presence of near-visible light. We present in detail the mechanism of electron transfer in biotic and abiotic systems during light exposure. Through this example we show that FSP is a versatile technique for efficiently designing a homologous library, meaning a library based on a parent oxide doped with different amounts of dopant, and investigating the properties of the resulting compounds.Finally, we describe the future outlook and state-of-the-art of an innovative two-flame system. A double-flame reactor enables independent control over each flame, the nozzle distances and the flame angles for efficient mixing of the particle streams. In addition, it allows for different flame compositions, flame sizes, and multicomponent mixing (a grain–grain heterojunction) during the reaction process
Contact Forces between TiO<sub>2</sub> Nanoparticles Governed by an Interplay of Adsorbed Water Layers and Roughness
Interparticle forces govern the mechanical
behavior of granular
matter and direct the hierarchical assembling of nanoparticles into
supramolecular structures. Understanding how these forces change under
different ambient conditions would directly benefit industrial-scale
nanoparticle processing units such as filtering and fluidization.
Here we rationalize and quantify the contributions of dispersion,
capillary, and solvation forces between hydrophilic TiO<sub>2</sub> nanoparticles with sub-10 nm diameter and show that the humidity
dependence of the interparticle forces is governed by a delicate interplay
between the structure of adsorbed water layers and the surface roughness.
All-atom molecular dynamics modeling supported by force-spectroscopy
experiments reveals an unexpected decrease in the contact forces at
increasing humidity for nearly spherical particles, while the forces
between rough particles are insensitive to strong humidity changes.
Our results also frame the limits of applicability of discrete solvation
and continuum capillary theories in a regime where interparticle forces
are dominated by the molecular nature of surface adsorbates
Determination of the Flat Band Potential of Nanoparticles in Porous Electrodes by Blocking the Substrate–Electrolyte Contact
The determination of the flat band
potential of metal oxide nanoparticles is essential to understand
their electrochemical behavior in aqueous environments. The electrochemical
behavior determines the possible applications and governs the environmental
impact of a nanomaterial. Hence, a new electrode fabrication method
is demonstrated that allows determining the flat band potential of
nanoparticles in porous nanoparticle electrodes via electrochemical
impedance spectroscopy. In such electrodes, the electrolyte is in
contact with the substrate material and contributes significantly
to the ac response of the entire electrode. To block the substrate–electrolyte
contact, the nanoparticle layers were imbibed in a liquid diacrylate
monomer, followed by polymerization. To reestablish the contact between
the outermost polymer-covered particles and the electrolyte, an O<sub>2</sub> plasma treatment was conducted. Based on this new electrode
fabrication procedure, the flat band potential of TiO<sub>2</sub>,
WO<sub>3</sub>, and Co<sub>3</sub>O<sub>4</sub> nanoparticles in porous
electrodes was determined with high precision. We believe that this
new and economical method will offer an alternative to expensive ultraviolet
photoelectron spectroscopy measurements at synchrotron facilities
The Fate of ZnO Nanoparticles Administered to Human Bronchial Epithelial Cells
A particular challenge for nanotoxicology is the evaluation of the biological fate and toxicity of nanomaterials that dissolve in aqueous fluids. Zinc oxide nanomaterials are of particular concern because dissolution leads to release of the toxic divalent zinc ion. Although zinc ions have been implicated in ZnO cytotoxicity, direct identification of the chemical form of zinc taken up by cells exposed to ZnO nanoparticles, and its intracellular fate, has not yet been achieved. We combined high resolution X-ray spectromicroscopy and high elemental sensitivity X-ray microprobe analyses to determine the fate of ZnO and less soluble iron-doped ZnO nanoparticles following exposure to cultures of human bronchial epithelial cells, BEAS-2B. We complemented two-dimensional X-ray imaging methods with atomic force microscopy of cell surfaces to distinguish between nanoparticles that were transported inside the cells from those that adhered to the cell exterior. The data suggest cellular uptake of ZnO nanoparticles is a mechanism of zinc accumulation in cells. Following uptake, ZnO nanoparticles dissolved completely generating intracellular Zn<sup>2+</sup> complexed by molecular ligands. These results corroborate a model for ZnO nanoparticle toxicity that is based on nanoparticle uptake followed by intracellular dissolution
Screening Precursor–Solvent Combinations for Li<sub>4</sub>Ti<sub>5</sub>O<sub>12</sub> Energy Storage Material Using Flame Spray Pyrolysis
The development and
industrial application of advanced lithium based energy-storage materials
are directly related to the innovative production techniques and the
usage of inexpensive precursor materials. Flame spray pyrolysis (FSP)
is a promising technique that overcomes the challenges in the production
processes such as scalability, process control, material versatility,
and cost. In the present study, phase pure anode material Li<sub>4</sub>Ti<sub>5</sub>O<sub>12</sub> (LTO) was designed using FSP via extensive
systematic screening of lithium and titanium precursors dissolved
in five different organic solvents. The effect of precursor and solvent
parameters such as chemical reactivity, boiling point, and combustion
enthalpy on the particle formation either via gas-to-particle (evaporation/nucleation/growth)
or via droplet-to-particle (precipitation/incomplete evaporation)
is discussed. The presence of carboxylic acid in the precursor solution
resulted in pure (>95 mass %) and homogeneous LTO nanoparticles
of size 4–9 nm, attributed to two reasons: (1) stabilization
of water sensitive metal alkoxides precursor and (2) formation of
volatile carboxylates from lithium nitrate evidenced by attenuated
total reflection Fourier transform infrared spectroscopy and single
droplet combustion experiments. In contrast, the absence of carboxylic
acids resulted in larger inhomogeneous crystalline titanium dioxide
(TiO<sub>2</sub>) particles with significant reduction of LTO content
as low as ∼34 mass %. In-depth particle characterization was
performed using X-ray diffraction with Rietveld refinement, thermogravimetric
analysis coupled with differential scanning calorimetry and mass spectrometry,
gas adsorption, and vibrational spectroscopy. High-resolution transmission
electron microscopy of the LTO product revealed excellent quality
of the particles obtained at high temperature. In addition, high rate
capability and efficient charge reversibility of LTO nanoparticles
demonstrate the vast potential of inexpensive gas-phase synthesis
for energy-storage materials
Safe-by-Design CuO Nanoparticles <i>via</i> 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 <i>vs</i> 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<sup>+</sup>/Cu<sup>2+</sup> and Fe<sup>2+</sup>/Fe<sup>3+</sup> 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 <i>via</i> Fe doping
and has been demonstrated for their safe use in the environment
Toxicity of Metal Oxide Nanoparticles in Escherichia coli Correlates with Conduction Band and Hydration Energies
Metal
oxide nanoparticles (MO<sub><i>x</i></sub> NPs) are used
for a host of applications, such as electronics, cosmetics, construction,
and medicine, and as a result, the safety of these materials to humans
and the environment is of considerable interest. A prior study of
24 MO<sub><i>x</i></sub> NPs in mammalian cells revealed
that some of these materials show hazard potential. Here, we report
the growth inhibitory effects of the same series of MO<sub><i>x</i></sub> NPs in the bacterium Escherichia
coli and show that toxicity trends observed in E. coli parallel those seen previously in mammalian
cells. Of the 24 materials studied, only ZnO, CuO, CoO, Mn<sub>2</sub>O<sub>3</sub>, Co<sub>3</sub>O<sub>4</sub>, Ni<sub>2</sub>O<sub>3</sub>, and Cr<sub>2</sub>O<sub>3</sub> were found to exert significant
growth inhibitory effects; these effects were found to relate to membrane
damage and oxidative stress responses in minimal trophic media. A
correlation of the toxicological data with physicochemical parameters
of MO<sub><i>x</i></sub> NPs revealed that the probability
of a MO<sub><i>x</i></sub> NP being toxic increases as the hydration enthalpy becomes less negative and as the conduction band energy approaches
those of biological molecules. These observations are consistent with
prior results observed in mammalian cells, revealing that mechanisms
of toxicity of MO<sub><i>x</i></sub> NPs are consistent
across two very different taxa. These results suggest that studying
nanotoxicity in E. coli may help to
predict toxicity patterns in higher organisms
PdO Doping Tunes Band-Gap Energy Levels as Well as Oxidative Stress Responses to a Co<sub>3</sub>O<sub>4</sub> <i>p</i>‑Type Semiconductor in Cells and the Lung
We demonstrate through PdO doping
that creation of heterojunctions
on Co<sub>3</sub>O<sub>4</sub> nanoparticles can quantitatively adjust
band-gap and Fermi energy levels to study the impact of metal oxide
nanoparticle semiconductor properties on cellular redox homeostasis
and hazard potential. Flame spray pyrolysis (FSP) was used to synthesize
a nanoparticle library in which the gradual increase in the PdO content
(0–8.9%) allowed electron transfer from Co<sub>3</sub>O<sub>4</sub> to PdO to align Fermi energy levels across the heterojunctions.
This alignment was accompanied by free hole accumulation at the Co<sub>3</sub>O<sub>4</sub> interface and production of hydroxyl radicals.
Interestingly, there was no concomitant superoxide generation, which
could reflect the hole dominance of a <i>p</i>-type semiconductor.
Although the electron flux across the heterojunctions induced upward
band bending, the <i>E</i><sub>c</sub> levels of the doped
particles showed energy overlap with the biological redox potential
(BRP). This allows electron capture from the redox couples that maintain
the BRP from −4.12 to −4.84 eV, causing disruption of
cellular redox homeostasis and induction of oxidative stress. PdO/Co<sub>3</sub>O<sub>4</sub> nanoparticles showed significant increases in
cytotoxicity at 25, 50, 100, and 200 μg/mL, which was enhanced
incrementally by PdO doping in BEAS-2B and RAW 264.7 cells. Oxidative
stress presented as a tiered cellular response involving superoxide
generation, glutathione depletion, cytokine production, and cytotoxicity
in epithelial and macrophage cell lines. A progressive series of acute
pro-inflammatory effects could also be seen in the lungs of animals
exposed to incremental PdO-doped particles. All considered, generation
of a combinatorial PdO/Co<sub>3</sub>O<sub>4</sub> nanoparticle library
with incremental heterojunction density allowed us to demonstrate
the integrated role of <i>E</i><sub>v</sub>, <i>E</i><sub>c</sub>, and <i>E</i><sub>f</sub> levels in the generation
of oxidant injury and inflammation by the <i>p</i>-type
semiconductor, Co<sub>3</sub>O<sub>4</sub>
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-1β
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-1β 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
Use of Metal Oxide Nanoparticle Band Gap To Develop a Predictive Paradigm for Oxidative Stress and Acute Pulmonary Inflammation
We demonstrate for 24 metal oxide (MOx) nanoparticles that it is possible to use conduction band energy levels to delineate their toxicological potential at cellular and whole animal levels. Among the materials, the overlap of conduction band energy (<i>E</i><sub>c</sub>) levels with the cellular redox potential (−4.12 to −4.84 eV) was strongly correlated to the ability of Co<sub>3</sub>O<sub>4</sub>, Cr<sub>2</sub>O<sub>3</sub>, Ni<sub>2</sub>O<sub>3</sub>, Mn<sub>2</sub>O<sub>3</sub>, and CoO nanoparticles to induce oxygen radicals, oxidative stress, and inflammation. This outcome is premised on permissible electron transfers from the biological redox couples that maintain the cellular redox equilibrium to the conduction band of the semiconductor particles. Both single-parameter cytotoxic as well as multi-parameter oxidative stress assays in cells showed excellent correlation to the generation of acute neutrophilic inflammation and cytokine responses in the lungs of C57 BL/6 mice. Co<sub>3</sub>O<sub>4</sub>, Ni<sub>2</sub>O<sub>3</sub>, Mn<sub>2</sub>O<sub>3</sub>, and CoO nanoparticles could also oxidize cytochrome <i>c</i> as a representative redox couple involved in redox homeostasis. While CuO and ZnO generated oxidative stress and acute pulmonary inflammation that is not predicted by <i>E</i><sub>c</sub> levels, the adverse biological effects of these materials could be explained by their solubility, as demonstrated by ICP-MS analysis. These results demonstrate that it is possible to predict the toxicity of a large series of MOx nanoparticles in the lung premised on semiconductor properties and an integrated <i>in vitro</i>/<i>in vivo</i> hazard ranking model premised on oxidative stress. This establishes a robust platform for modeling of MOx structure–activity relationships based on band gap energy levels and particle dissolution. This predictive toxicological paradigm is also of considerable importance for regulatory decision-making about this important class of engineered nanomaterials