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Review
. 2016 Mar 21;45(6):1750-80.
doi: 10.1039/c5cs00914f.

Biological and environmental interactions of emerging two-dimensional nanomaterials

Zhongying Wang  1 , Wenpeng Zhu  1 , Yang Qiu  1 , Xin Yi  1 , Annette von dem Bussche  2 , Agnes Kane  3 , Huajian Gao  1 , Kristie Koski  4 , Robert Hurt  5
Affiliations
Review

Biological and environmental interactions of emerging two-dimensional nanomaterials

Zhongying Wang et al. Chem Soc Rev. .

Abstract

Two-dimensional materials have become a major focus in materials chemistry research worldwide with substantial efforts centered on synthesis, property characterization, and technological application. These high-aspect ratio sheet-like solids come in a wide array of chemical compositions, crystal phases, and physical forms, and are anticipated to enable a host of future technologies in areas that include electronics, sensors, coatings, barriers, energy storage and conversion, and biomedicine. A parallel effort has begun to understand the biological and environmental interactions of synthetic nanosheets, both to enable the biomedical developments and to ensure human health and safety for all application fields. This review covers the most recent literature on the biological responses to 2D materials and also draws from older literature on natural lamellar minerals to provide additional insight into the essential chemical behaviors. The article proposes a framework for more systematic investigation of biological behavior in the future, rooted in fundamental materials chemistry and physics. That framework considers three fundamental interaction modes: (i) chemical interactions and phase transformations, (ii) electronic and surface redox interactions, and (iii) physical and mechanical interactions that are unique to near-atomically-thin, high-aspect-ratio solids. Two-dimensional materials are shown to exhibit a wide range of behaviors, which reflect the diversity in their chemical compositions, and many are expected to undergo reactive dissolution processes that will be key to understanding their behaviors and interpreting biological response data. The review concludes with a series of recommendations for high-priority research subtopics at the "bio-nanosheet" interface that we hope will enable safe and successful development of technologies related to two-dimensional nanomaterials.

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Figures

Figure 1
Figure 1
Diversity in chemistry and morphology of 2D and layered materials. Right: Classification of 2D materials used in this review. Morphology (thickness and lateral dimension) together with chemical composition and phase are co-determinants of biological and environmental behavior. Left: Examples of 2D and layered material compositions, illustrating the high degree of chemical diversity.
Figure 2
Figure 2
Exposure types and pathways for emerging 2D nanomaterials. Most behaviors and issues are similar to those for particulate nanomaterials, but there are also distinctive 2D behaviors as shown here, such as physical transformations by folding, wrinkling, and restacking, and the importance of hazardous chemical byproducts and reductive dissolution processes associated with the particular chemical compositions of some important inorganic nanosheet materials.
Figure 3
Figure 3
Common synthetic routes to 2D materials. (a) Vapor-phase synthesis, (b) solvothermal/hydrothermal solution synthesis, (c) colloidal solution-based growth. (d) Example Bi2Se3 plates (1–5nm thick) synthesized through solvothermal growth. Adapted with permission from ref. . Copyright 2013 American Chemical Society. (e) MoO3 nanoribbons synthesized through hydrothermal growth. Adapted with permission from ref. . Copyright 2015 American Chemical Society. (f) vapor-phase synthesized silicon telluride, Si2Te3. Adapted with permission from ref. . Copyright 2015 American Chemical Society.
Figure 4
Figure 4
In vivo clearance of elemental Bi and Se and oxidation/dissolution of Bi2Se3 nanosheets. Time-depnedent decrease of Bi concentratoin (a) and Se concentration (b) caused by clearance effects. Digital image (c) and XRD spectrum of the oxidized Bi2Se3 nanosheets after exposure to air for 30 days (d). (e) Illustration showing dissolution and oxidation of the Bi2Se3 nanosheets after intraperitoneal injection. Reprinted with permission from ref. . Copyright 2013, John Wiley & Sons, Inc.
Figure 5
Figure 5
Structure and human health effects of sheet-like silicate minerals. Table 2 summarizes the known pathological responses to inhalation as a function of material type. (a) Crystal structure of chrysotile asbestos. Reprinted with permission from ref. . Copyright 2004, Springer. (b) Crystal structure of kaolinite, which is a 2D silicate clay mineral. (c) Lattice of crystalline silica or α-quartz. Fracturing the crystal along the arrows generates highly reactive Si• or SiO• dangling bonds on the new surface. Reprinted with permission from ref. . Copyright 1996, Taylor & Francis.
Figure 6
Figure 6
Fundamental modes of interaction between 2D materials and biological systems. The arrows show the bidirectionality of the interactions, in which the biological environment induces chemical or physical material transformations, while the materials and/or their transformation products induce biological responses.
Figure 7
Figure 7
Dissolution behaviors of 2D nanomaterials. (a) Three dissolution mechanisms in biological and environmental media. (b) Equilibrium solubilities of metal sulfides, oxides, hydroxides and LDHs at pH 7 based on solubility constants for metal hydroxides and LAHs, or Visual MINTEQ 3.1 for metal oxides and sulfides at pH 7 with 1 mM NaNO3 as electrolyte. (c) Criterion for oxidative dissolution: comparison of 2D material oxidation potentials with the water/O2 redox couple (pH 7), suggesting that MoS2, MoSe2, WS2 and WSe2 are likely to be oxidatively unstable. (d) Criterion for reductive dissolution: comparison of 2D material reduction potential with the cellular redox potential (exemplified by GSH/GSSG couple) at pH 7, suggesting WO3, MoO3 and MnO2 are unstable to biological reduction and dissolution.
Figure 8
Figure 8
Physical and mechanical modes of 2D material bio-interactions, illustrated using data on graphene (G) and graphene oxide (GO). (a) Experimental observation and molecular dynamics simulations on the destructive extractions of lipid molecules from E. coli lipid membranes after incubations with graphene nanosheets. Reprinted by permission from Macmillan Publishers Ltd: Nat. Nanotechnol., copyright 2013. (b) A pristine graphene nanoflake (6×6 nm) aligns parallel at the interface between two lipid monolayers. Reprinted with permission from ref. . Copyright 2009 American Chemical Society. (c) A graphene nanoflake (5.5×6 nm) with 10% of edge carbon atoms oxidized adopts a near-perpendicular transmembrane configuration. The lipid molecules are shown in cyan with green head groups. Reproduced from Ref. with permission from The Royal Society of Chemistry. Corner penetration (d) and edge penetration (e) of a graphene microsheet into a primary human keratinocyte. Copyright (2013) National Academy of Sciences, USA. (f) Protein-coated GO sheets adhere parallel onto the surface of mouse C2C12 mesenchymal cells followed by subsequent cellular internalization. Reprinted with permission from ref. . Copyright 2012 American Chemical Society. (g) Large GO sheets (yellow arrow) attach to the plasma membrane of fish liver cells (PLHC-1). Wrinkles are formed due to the large lateral size of the adhering GO sheets. Reprinted with permission from ref. . Copyright 2012 Elsevier Ltd. (h) After initial internalization by peritoneal macrophages, GO sheets of lateral size 2 µm undergo significant deformation and exhibit wrinkling. Reprinted with permission from ref. . Copyright 2012 Elsevier Ltd. (i) Few-layer graphene sheets wrap around human THP-1 macrophages. (j) Human THP-1 macrophages adhere to and then spread along the surface of 25 µm few-layer graphene sheets. (i) and (j) reprinted with permission from ref. . Copyright 2012 American Chemical Society. (k) AFM images of E. coli cells covered by large GO sheets of average lateral size 13 µm2. Reprinted with permission from ref. . Copyright 2012 American Chemical Society. The central panel is a schematic representation of the above interaction modes (a-k) as well as endocytosis (l) by which (multilayer) 2D materials could possibly enter the cell.
Figure 9
Figure 9
Mechanical interaction between an internalized circular sheet of diameter L and a surrounding vesicle of effective radius a at zero osmotic pressure. (a) Compressive contact force f between the vesicle membrane and encapsulated sheet (assumed to be rigid in the contact force calculation). (b) Buckling phase diagram with respect to the length ratio L/(2a) and bending stiffness ratio κp/κ. Insets in (a) correspond to the vesicle configurations at L/(2a)=1.1 and 1.3. Colored strips in (b) mark the regimes in which the corresponding 2D materials would buckle beyond a critical length. Except the bilayer MoS2 in the magenta regime, the other 2D materials marked in (b) are of monolayer structures. In the case of lateral size L<2a, the encapsulated 2D material would undergo random Brownian motion in the vesicular confinement.
Figure 10
Figure 10
Band structures of 2D and bulk layered materials, and band alignment with the cellular redox potential and the ROS-involved redox couples. (a) Cellular redox potential range defined by biomolecular redox couples. Reprinted with permission from ref. . Copyright 2006 Mineralogical Society of America. (b) The illustration of platform for modeling of structure–activity relationships based on band structures. Reprinted with permission from ref. Copyright 2012 American Chemical Society. (c) The comparison a physicochemical in silico screening tool for identifying specific 2D materials with high potential for biological redox activity. Construction of the framework is based on published data in graphite, single wall carbon nanotubes, TMD, h-BN, MnO2 nanosheets, lepidocrocite-type TiO2 nanosheets, MoO3 and WO3, and ROS-involved redox couples.
Figure 11
Figure 11
(a, c) Optical microscopy (100×) and (b, d) AFM image of exfoliated MoS2 nanosheets before (top) and after (bottom) laser line scan, showing edge sites are the primary targets of photodegradation. e) Normalized Raman peak area as a function of illumination time on the edge site of a bilayer flake in the electrolyte with reduced oxygen (blue) and natural amount of dissolved oxygen (red). Reprinted with permission from ref. . Copyright 2015 American Chemical Society. (e) Proposed model for the evolution of redox chemistry in the photoreduction of MnO2 monolayer including photon absorption, formation of distorted Mn (III), migration of Mn(III) to an adsorption site and increased nanosheet stacking. Copyright (2015) National Academy of Sciences, USA.
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