Graphene is a single-atom thick, two-dimensional sheet of hexagonally arranged carbon atoms isolated from its three-dimensional parent material, graphite. Related materials include few-layer-graphene (FLG), ultrathin graphite, graphene oxide (GO), reduced graphene oxide (rGO), and graphene nanosheets (GNS). This review proposes a systematic nomenclature for this set of “Graphene-Family Nanomaterials” (GFNs) and discusses specific materials properties relevant for biomolecular and cellular interactions. The article discusses several unique modes of interaction between GFNs and nucleic acids, lipid bilayers, and conjugated small molecule drugs and dyes. Some GFNs are produced as dry powders using thermal exfoliation, and in these cases inhalation is a likely route of human exposure. Some GFNs have aerodynamic sizes that can lead to inhalation and substantial deposition in the human respiratory tract, which may impair lung defense and clearance leading to formation of granulomas and lung fibrosis. The limited literature on in vitro toxicity suggests that GFNs can be either benign or toxic to cells, and it is hypothesized that the biological response will vary across the material family depending on layer number, lateral size, stiffness, hydrophobicity, surface functionalization, and dose. Generation of reactive oxygen species (ROS) in target cells is a potential mechanism for toxicity, although the extremely high hydrophobic surface area of some GFNs may also lead to significant interactions with membrane lipids leading to direct physical toxicity or adsorption of biological molecules leading to indirect toxicity. Limited in vivo studies demonstrate systemic biodistribution and biopersistence of GFNs following intravenous delivery. Similar to other smooth, continuous, biopersistent implants or foreign bodies, GFNs have the potential to induce foreign body tumors. Long-term adverse health impacts must be considered in design of GFNs for drug delivery, tissue engineering, and fluorescence-based biomolecular sensing. Future research is needed to explore fundamental biological responses to GFNs including systematic assessment of the physical and chemical materials properties related to toxicity. Complete materials characterization and mechanistic toxicity studies are essential for safer design and manufacturing of GFNs in order to optimize biological applications with minimal risks for environmental health and safety.

Water microdroplets containing graphene oxide and a second solute are shown to spontaneously segregate into sack-cargo nanostructures upon drying. Analytical modelling and molecular dynamics suggest the sacks form when slow-diffusing graphene oxide preferentially accumulates and adsorbs at the receding air-water interface, followed by capillary collapse. Cargo-filled graphene nanosacks can be nanomanufactured by a simple, continuous, scalable process and are promising for many applications where nanoscale materials should be isolated from the environment or biological tissue.

As graphene technologies progress to commercialization and large-scale manufacturing, issues of material and processing safety will need to be more seriously considered. The single word “graphene” actually represents a family of related materials with large variations in number of layers, surface area, lateral dimensions, stiffness, and surface chemistry. Many of these materials have aerodynamic diameters below 5 μm and can potentially be inhaled into the human lung. Graphene materials show several unique modes of interaction with biological molecules, tissues, and cells. The limited literature suggests that graphene materials can be either benign or harmful and that the biological response varies according to a material’s physicochemical properties and biologically effective dose. The present article reviews the current literature on the graphene–biological interface with an emphasis on the mechanisms and fundamental biological responses relevant to material safety and also to potential biomedical applications

Whether mucus layers lining entrance points into the body, including the lung airways, provide protection against the penetration of engineered nanoparticles remains poorly understood. We measured the diffusion coefficients of hundreds of individual nanoparticles of three different metal oxides (nMeOs) and two types of single-walled carbon nanotubes (SWCNTs) in undiluted human mucus. We found that the vast majority of these nanoparticles are efficiently trapped in human mucus and, further, that the mechanism of trapping is adhesive interactions as opposed to steric obstruction. However, a small fraction of zinc oxide (ZnO) nanoparticles moved at rates fast enough to penetrate airway mucus layers. We conclude that human mucus layers probably provide considerable protection for mucosal tissues from the penetration of most nMeOs and SWCNTs, and suggest that further investigation of the potential health risks of exposure to ZnO nanoparticles is warranted.