Zhongying Wang

Chemical Transformations of Nanosilver in Biological Environments

The widespread use of silver nanoparticles (Ag-NPs) in consumer and medical products provides strong motivation for a careful assessment of their environmental and human health risks. Recent studies have shown that Ag-NPs released to the natural environment undergo profound chemical transformations that can affect silver bioavailability, toxicity, and risk. Less is known about Ag-NP chemical transformations in biological systems, though the medical literature clearly reports that chronic silver ingestion produces argyrial deposits consisting of silver-, sulfur-, and selenium-containing particulate phases. Here we show that Ag-NPs undergo a rich set of biochemical transformations, including accelerated oxidative dissolution in gastric acid, thiol binding and exchange, photoreduction of thiol- or protein-bound silver to secondary zerovalent Ag-NPs, and rapid reactions between silver surfaces and reduced selenium species. Selenide is also observed to rapidly exchange with sulfide in preformed Ag(2)S solid phases. The combined results allow us to propose a conceptual model for Ag-NP transformation pathways in the human body. In this model, argyrial silver deposits are not translocated engineered Ag-NPs, but rather secondary particles formed by partial dissolution in the GI tract followed by ion uptake, systemic circulation as organo-Ag complexes, and immobilization as zerovalent Ag-NPs by photoreduction in light-affected skin regions. The secondary Ag-NPs then undergo detoxifying transformations into sulfides and further into selenides or Se/S mixed phases through exchange reactions. The formation of secondary particles in biological environments implies that Ag-NPs are not only a product of industrial nanotechnology but also have long been present in the human body following exposure to more traditional chemical forms of silver.

Biological and Environmental Transformations of Copper-Based Nanomaterials

Copper-based nanoparticles are an important class of materials with applications as catalysts, conductive inks, and antimicrobial agents. Environmental and safety issues are particularly important for copper-based nanomaterials because of their potential large-scale use and their high redox activity and toxicity reported from in vitro studies. Elemental nanocopper oxidizes readily upon atmospheric exposure during storage and use, so copper oxides are highly relevant phases to consider in studies of environmental and health impacts. Here we show that copper oxide nanoparticles undergo profound chemical transformations under conditions relevant to living systems and the natural environment. Copper oxide nanoparticle (CuO-NP) dissolution occurs at lysosomal pH (4-5), but not at neutral pH in pure water. Despite the near-neutral pH of cell culture medium, CuO-NPs undergo significant dissolution in media over time scales relevant to toxicity testing because of ligand-assisted ion release, in which amino acid complexation is an important contributor. Electron paramagnetic resonance (EPR) spectroscopy shows that dissolved copper in association with CuO-NPs are the primary redox-active species. CuO-NPs also undergo sulfidation by a dissolution-reprecipitation mechanism, and the new sulfide surfaces act as catalysts for sulfide oxidation. Copper sulfide NPs are found to be much less cytotoxic than CuO-NPs, which is consistent with the very low solubility of CuS. Despite this low solubility of CuS, EPR studies show that sulfidated CuO continues to generate some ROS activity due to the release of free copper by H2O2 oxidation during the Fenton-chemistry-based EPR assay. While sulfidation can serve as a natural detoxification process for nanosilver and other chalcophile metals, our results suggest that sulfidation may not fully and permanently detoxify copper in biological or environmental compartments that contain reactive oxygen species.

Chemical Dissolution Pathways of MoS2 Nanosheets in Biological and Environmental Media.

Material stability and dissolution in aqueous media are key issues to address in the development of a new nanomaterial intended for technological application. Dissolution phenomena affect biological and environmental persistence; fate, transport, and biokinetics; device and product stability; and toxicity pathways and mechanisms. This article shows that MoS2 nanosheets are thermodynamically and kinetically unstable to O2-oxidation under ambient conditions in a variety of aqueous media. The oxidation is accompanied by nanosheet degradation and release of soluble molybdenum and sulfur species, and generates protons that can colloidally destabilize the remaining sheets. The oxidation kinetics are pH-dependent, and a kinetic law is developed for use in biokinetic and environmental fate modeling. MoS2 nanosheets fabricated by chemical exfoliation with n-butyl-lithium are a mixture of 1T (primary) and 2H (secondary) phases and oxidize rapidly with a typical half-life of 1-30 days. Ultrasonically exfoliated sheets are in pure 2H phase, and oxidize much more slowly. Cytotoxicity experiments on MoS2 nanosheets and molybdate ion controls reveal the relative roles of the nanosheet and soluble fractions in the biological response. These results indicate that MoS2 nanosheets will not show long-term persistence in living systems and oxic natural waters, with important implications for biomedical applications and environmental risk.

Nanomechanical mechanism for lipid bilayer damage induced by carbon nanotubes confined in intracellular vesicles

Significance Recent experimental studies report correlations between carbon nanotube toxicity and tube length and stiffness. Very little is known, however, about the actual behavior of these fibrous nanomaterials inside living cells following uptake, and the fundamental mechanistic link between stiffness and toxicity is unclear. Here we reveal a nanomechanical mechanism by which sufficiently long and stiff carbon nanotubes damage lysosomes, a class of membrane-enclosed organelles found inside cells that are responsible for breaking down diverse biomolecules and debris. The precise material parameters needed to activate this unique mechanical toxicity pathway are identified through coupled theoretical modeling, molecular dynamics simulations, and experimental studies, leading to a predictive pathogenicity classification diagram that distinguishes toxic from biocompatible nanomaterials based on their geometry and stiffness. Understanding the behavior of low-dimensional nanomaterials confined in intracellular vesicles has been limited by the resolution of bioimaging techniques and the complex nature of the problem. Recent studies report that long, stiff carbon nanotubes are more cytotoxic than flexible varieties, but the mechanistic link between stiffness and cytotoxicity is not understood. Here we combine analytical modeling, molecular dynamics simulations, and in vitro intracellular imaging methods to reveal 1D carbon nanotube behavior within intracellular vesicles. We show that stiff nanotubes beyond a critical length are compressed by lysosomal membranes causing persistent tip contact with the inner membrane leaflet, leading to lipid extraction, lysosomal permeabilization, release of cathepsin B (a lysosomal protease) into the cytoplasm, and cell death. The precise material parameters needed to activate this unique mechanical pathway of nanomaterials interaction with intracellular vesicles were identified through coupled modeling, simulation, and experimental studies on carbon nanomaterials with wide variation in size, shape, and stiffness, leading to a generalized classification diagram for 1D nanocarbons that distinguishes pathogenic from biocompatible varieties based on a nanomechanical buckling criterion. For a wide variety of other 1D material classes (metal, oxide, polymer), this generalized classification diagram shows a critical threshold in length/width space that represents a transition from biologically soft to stiff, and thus identifies the important subset of all 1D materials with the potential to induce lysosomal permeability by the nanomechanical mechanism under investigation.

From Flatland to Spaceland: Higher Dimensional Patterning with Two-Dimensional Materials

The creation of three-dimensional (3D) structures from two-dimensional (2D) nanomaterial building blocks enables novel chemical, mechanical or physical functionalities that cannot be realized with planar thin films or in bulk materials. Here, we review the use of emerging 2D materials to create complex out-of-plane surface topographies and 3D material architectures. We focus on recent approaches that yield periodic textures or patterns, and present four techniques as case studies: (i) wrinkling and crumpling of planar sheets, (ii) encapsulation by crumpled nanosheet shells, (iii) origami folding and kirigami cutting to create programmed curvature, and (iv) 3D printing of 2D material suspensions. Work to date in this field has primarily used graphene and graphene oxide as the 2D building blocks, and we consider how these unconventional approaches may be extended to alternative 2D materials and their heterostructures. Taken together, these emerging patterning and texturing techniques represent an intriguing alternative to conventional materials synthesis and processing methods, and are expected to contribute to the development of new composites, stretchable electronics, energy storage devices, chemical barriers, and biomaterials.

Aerosol synthesis of phase-controlled iron–graphene nanohybrids through FeOOH nanorod intermediates

Iron-based nanoparticles form the basis for a host of sustainable alternative technologies based on this earth-abundant, low-toxicity element that can adopt a variety of oxidation states, crystal phases, and functions. Control of size, shape, and phase stability is a challenge for many nano-iron-based technologies, especially those involving Fe0 that is susceptible to oxidation under ambient conditions. This article presents a continuous method for hybridizing Fe-based nanoparticles with carbon in the form of graphene-encapsulated Fe-based particles with core-shell symmetry that allows flexible control of iron particle size, shape, and phase stability. The method uses FeOOH nanorods and graphene oxide as precursors, and subjects them to an aerosol-phase microdroplet drying and annealing process to yield a range of Fe/C nanohybrids whose structure can be controlled through adjustment of aerosol process temperature and post-synthesis thermal treatment conditions. We demonstrate that FeOOH nanorods can be successfully encapsulated in graphene, and transform during annealing into encapsulated Fe3O4 or Fe0 nanoparticles by reductive fragmentation, where the graphene nanosack acts as a carbothermic reductant. The hybrids are characterized by vibrating sample magnetometry and Cr(VI) reduction rates in aqueous media. The Fe0-graphene hybrids show high activity, good stability, and good recyclability in aqueous Cr(VI) removal due to the effect of graphene encapsulation. The present work suggests this rapid and continuous synthesis method can produce stable Fe-based materials, and can be extended to other metal systems, where graphene encapsulation can induce in situ reduction of metal oxide precursors into zero-valent metal-graphene hybrids.

Graphene Topographies: Multiscale Graphene Topographies Programmed by Sequential Mechanical Deformation (Adv. Mater. 18/2016).

P.-Y. Chen, R. H. Hurt, I. Y. Wong and co-workers demonstrate a hierarchical graphene surface architecture generated by using various sequences and combinations of extreme mechanical deformation, as shown in the false-colored SEM image. As described on page 3564, the sequential patterning approach enables the design of feature sizes and orientations across multiple length scales which are retained during mechanical deformations of similar extent. This results in sequence-dependent surface topographies with structural memory.

Aerosol synthesis and application of folded graphene-based materials

Graphene oxide colloid has been widely used in the synthesis of various graphene-based materials. Graphene oxide sheets, with a low bending rigidity, can be folded when assembled in aqueous phase. A simple but industrial scalable way, aerosol processing, can be used to fabricate folded graphene-based materials. These folded materials can carry various cargo materials and be used in different applications such as time-controlled drug release, medical imaging enhancement, catalyst support and energy related areas. The aerosol synthesis of folded graphene-based materials can also be easily extended to fabricate hybrid nanomaterials without any complicated chemistries.