Graphene and its derivatives are heralded as “miracle” materials with manifold applications in different sectors of society from electronics to energy storage to medicine. The increasing exploitation of graphene-based materials (GBMs) necessitates a comprehensive evaluation of the potential impact of these materials on human health and the environment. Here, we discuss synthesis and characterization of GBMs as well as human and environmental hazard assessment of GBMs using in vitro and in vivo model systems with the aim to understand the properties that underlie the biological effects of these materials; not all GBMs are alike, and it is essential that we disentangle the structure–activity relationships for this class of materials.

Many consider carbon nanomaterials the poster children of nanotechnology, attracting immense scientific interest from many disciplines and offering tremendous potential in a diverse range of applications due to their extraordinary properties. Graphene is the youngest in the family of carbon nanomaterials. Its isolation, description, and mass fabrication has followed that of fullerenes and carbon nanotubes. Graphene's development and its adoption by many industries will increase unintended or intentional human exposure, creating the need to determine its safety profile. In this Account, we compare the lessons learned from the development of carbon nanotubes with what is known about graphene, based on our own investigations and those of others. Despite both being carbon-based, nanotubes and graphene are two very distinct nanomaterials. We consider the key physicochemical characteristics (structure, surface, colloidal properties) for graphene and carbon nanotubes at three different physiological levels: cellular, tissue, and whole body. We summarize the evidence for health effects of both materials at all three levels. Overall, graphene and its derivatives are characterized by a lower aspect ratio, larger surface area, and better dispersibility in most solvents compared to carbon nanotubes. Dimensions, surface chemistry, and impurities are equally important for graphene and carbon nanotubes in determining both mechanistic (aggregation, cellular processes, biodistribution, and degradation kinetics) and toxicological outcomes. Colloidal dispersions of individual graphene sheets (or graphene oxide and other derivatives) can easily be engineered without metallic impurities, with high stability and less aggregation. Very importantly, graphene nanostructures are not fiber-shaped. These features theoretically offer significant advantages in terms of safety over inhomogeneous dispersions of fiber-shaped carbon nanotubes. However, studies that directly compare graphene with carbon nanotubes are rare, making comparative considerations of their overall safety and risk assessment challenging. In this Account, we attempt to offer a set of rules for the development of graphene and its derivatives to enhance their overall safety and minimize the risks for adverse reactions in humans from exposure. These rules are: (1) to use small, individual graphene sheets that macrophages in the body can efficiently internalize and remove from the site of deposition; (2) to use hydrophilic, stable, colloidal dispersions of graphene sheets to minimize aggregation in vivo; and (3) to use excretable graphene material or chemically-modified graphene that can be degraded effectively. Such rules can only act as guidelines at this early stage in the development of graphene-based technologies, yet they offer a set of design principles for the fabrication and safe use of graphene material that will come in contact with the human body. In a broader context, the safety risks associated with graphene materials will be entirely dependent on the specific typ...

Stroke is the second cause of death worldwide with ischemic stroke accounting for 80% of all stroke insults. Caspase-3 activation contributes to brain tissue loss and downstream biochemical events that lead to programmed cell death after traumatic brain injury. Alleviation of symptoms following ischemic neuronal injury can be potentially achieved by either genetic disruption or pharmacological inhibition of caspases. Here, we studied whether silencing of Caspase-3 using carbon nanotube-mediated in vivo RNA interference (RNAi) could offer a therapeutic opportunity against stroke. Effective delivery of siRNA directly to the CNS has been shown to normalize phenotypes in animal models of several neurological diseases. It is shown here that peri-lesional stereotactic administration of a Caspase-3 siRNA (siCas 3) delivered by functionalized carbon nanotubes (f-CNT) reduced neurodegeneration and promoted functional preservation before and after focal ischemic damage of the rodent motor cortex using an endothelin-1 induced stroke model. These observations illustrate the opportunity offered by carbon nanotube-mediated siRNA delivery and gene silencing of neuronal tissue applicable to a variety of different neuropathological conditions where intervention at well localized brain foci may offer therapeutic and functional benefits.nanomedicine | neurodegenerative | neuroprotection | neurosciences | gene therapy

The occurrence of severe nanotube structure deformation leading to partial degradation of the chemically functionalized-multiwalled CNT-NH(3) (+) in vivo following internalization within microglia was revealed even at early time points. Such initial observations of CNT degradation within the brain tissue render further systematic investigations using high-resolution tools imperative.

The aim of this study was to evaluate adverse effects of multiwalled carbon nanotubes (MWCNT), produced for industrial purposes, on the human epithelial cell line A549. MWCNT were dispersed in dipalmitoyl lecithin (DPL), a component of pulmonary surfactant, and the effects of dispersion in DPL were compared to those in two other media: ethanol (EtOH) and phosphate-buffered saline (PBS). Effects of MWCNT were also compared to those of two asbestos fibers (chrysotile and crocidolite) and carbon black (CB) nanoparticles, not only in A549 cells but also in mesothelial cells (MeT5A human cell line), used as an asbestos-sensitive cell type. MWCNT formed agglomerates on top of both cell lines (surface area 15-35 microm(2)) that were significantly larger and more numerous in PBS than in EtOH and DPL. Whatever the dispersion media, incubation with 100 microg/ml MWCNT induced a similar decrease in metabolic activity without changing cell membrane permeability or apoptosis. Neither MWCNT cellular internalization nor oxidative stress was observed. In contrast, asbestos fibers penetrated into the cells, decreased metabolic activity but not cell membrane permeability, and increased apoptosis, without decreasing cell number. CB was internalized without any adverse effects. In conclusion, this study demonstrates that MWCNT produced for industrial purposes exert adverse effects without being internalized by human epithelial and mesothelial pulmonary cell lines.