Nanotoxicology Research Research Articles

Drosophotoxicology: An Emerging Research Area for Assessing Nanoparticles Interaction with Living Organisms.

The rapid development of nanotechnology allowed the fabrication of a wide range of different nanomaterials, raising many questions about their safety and potential risks for the human health and environment. Most of the current nanotoxicology research is not standardized, hampering any comparison or reproducibility of the obtained results. Drosophotoxicology encompasses the plethora of methodological approaches addressing the use of Drosophila melanogaster as a choice organism in toxicology studies. Drosophila melanogaster model offers several important advantages, such as a relatively simple genome structure, short lifespan, low maintenance cost, readiness of experimental manipulation comparative to vertebrate models from both ethical and technical points of view, relevant gene homology with higher organisms, and ease of obtaining mutant phenotypes. The molecular pathways, as well as multiple behavioral and developmental parameters, can be evaluated using this model in lower, medium or high throughput type assays, allowing a systematic classification of the toxicity levels of different nanomaterials. The purpose of this paper is to review the current research on the applications of Drosophila melanogaster model for the in vivo assessment of nanoparticles toxicity and to reveal the huge potential of this model system to provide results that could enable a proper selection of different nanostructures for a certain biomedical application.

MPQ-cytometry: a magnetism-based method for quantification of nanoparticle–cell interactions

Precise quantification of interactions between nanoparticles and living cells is among the imperative tasks for research in nanobiotechnology, nanotoxicology and biomedicine. To meet the challenge, a rapid method called MPQ-cytometry is developed, which measures the integral non-linear response produced by magnetically labeled nanoparticles in a cell sample with an original magnetic particle quantification (MPQ) technique. MPQ-cytometry provides a sensitivity limit 0.33 ng of nanoparticles and is devoid of a background signal present in many label-based assays. Each measurement takes only a few seconds, and no complicated sample preparation or data processing is required. The capabilities of the method have been demonstrated by quantification of interactions of iron oxide nanoparticles with eukaryotic cells. The total amount of targeted nanoparticles that specifically recognized the HER2/neu oncomarker on the human cancer cell surface was successfully measured, the specificity of interaction permitting the detection of HER2/neu positive cells in a cell mixture. Moreover, it has been shown that MPQ-cytometry analysis of a HER2/neu-specific iron oxide nanoparticle interaction with six cell lines of different tissue origins quantitatively reflects the HER2/neu status of the cells. High correlation of MPQ-cytometry data with those obtained by three other commonly used in molecular and cell biology methods supports consideration of this method as a prospective alternative for both quantifying cell-bound nanoparticles and estimating the expression level of cell surface antigens. The proposed method does not require expensive sophisticated equipment or highly skilled personnel and it can be easily applied for rapid diagnostics, especially under field conditions.

Emerging systems biology approaches in nanotoxicology: Towards a mechanism-based understanding of nanomaterial hazard and risk

Engineered nanomaterials are being developed for a variety of technological applications. However, the increasing use of nanomaterials in society has led to concerns about their potential adverse effects on human health and the environment. During the first decade of nanotoxicological research, the realization has emerged that effective risk assessment of the multitudes of new nanomaterials would benefit from a comprehensive understanding of their toxicological mechanisms, which is difficult to achieve with traditional, low-throughput, single end-point oriented approaches. Therefore, systems biology approaches are being progressively applied within the nano(eco)toxicological sciences. This novel paradigm implies that the study of biological systems should be integrative resulting in quantitative and predictive models of nanomaterial behaviour in a biological system. To this end, global ‘omics’ approaches with which to assess changes in genes, proteins, metabolites, etc. are deployed allowing for computational modelling of the biological effects of nanomaterials. Here, we highlight omics and systems biology studies in nanotoxicology, aiming towards the implementation of a systems nanotoxicology and mechanism-based risk assessment of nanomaterials.

Current situation and measures of safety culture in nano-laboratories

Nanotoxicology research demonstrated that some manufactured nanomaterials have toxic effects on human health and environment. For the worker exposed in nanolaboratories, nanomaterials present potential risks. Given the inadequate technologies for testing nanotoxicology, strengthening the safety culture and improving nanotechnology workers’ safety awareness are very important. Based on the empirical investigation, this paper explores firstly the current safety status in the nano-research laboratory from three dimensions: material culture,institution culture and awareness culture. Secondly, the paper puts forward some corresponding measures and suggestions. Lastly, the paper concludes that the construction of safety culture is not only vital for the health of nanotechnology researchers and the environment, but also important for the sustainable development of nanotechnology.

Copper nanoclusters trigger muscle cell apoptosis and atrophy in vitro and in vivo

Copper nanoclusters (CuNCs) are increasingly being used in nanomedicine owing to their utility in cellular imaging and as catalysts. Additionally, nanotoxicology research of CuNCs is gaining attention. We report here the synthesis and characterization of CuNCs and their cytotoxic impact on muscle cells. A simple protein-directed synthesis of stable CuNCs was prepared, using bovine serum albumin as the stabling agent. Physicochemical characterization of the synthesized CuNCs was performed using transmission electron microscopy. To evaluate the in vitro cytotoxicity, C2C12 cells were exposed to increasing doses (from 0.1 to 50 µg ml(-1)) of CuNCs. CuNCs affected the viability of C2C12 cells in a dose-dependent manner, as detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and a lactate dehydrogenase release assay. Further studies indicated that CuNCs induced the formation of reactive oxygen species and decreased the activities of catalase and glutathione. CuNC treatment decreased the mitochondrial membrane potential and induced apoptosis, accompanied by an increase in the protein expression ratio of Bax/Bcl-2 and caspase-3/9 activity in C2C12 cells. CuNCs treatment resulted in atrophy of the C2C12 myotubes, which was characterized by the increased expression of atrophy-related genes, such as atrogin-1 and MuRF1. Finally, CuNCs induce morphological atrophy of primary muscle cells and mouse gastrocnemius muscle. Taken together, these results suggest that exposure to CuNCs may be a risk factor for the skeletal muscle system.

Development of nanotoxicology: implications for drug delivery and medical devices.

Current nanotoxicology research suffers from suboptimal in vitro models, lack of in vitro-in vivo correlations, variability within in vitro protocols, deficits in both material purity and physicochemical characterization. Reliable nanomaterial toxicity and mechanistic insights are required for health and toxicity risk assessments. Much in vitro toxicological data is inconclusive in designating whether nanomaterials for drug delivery and medical device implants are truly safe. A critique is presented to analyze the interface between toxicology and nanopharmaceuticals. Deficiencies of existing practices in toxicology are reviewed and useful emerging techniques (e.g., lab-on-a-chip, tissue engineering, atomic force microscopy, high-content analysis) are highlighted. Cross-fertilization between disciplines will aid development of biocompatible delivery and implant platforms while improvements are being suggested for better translation of nanotoxicology.

Planktonic and biofilm-grown nitrogen-cycling bacteria exhibit different susceptibilities to copper nanoparticles.

Proper characterization of nanoparticle (NP) interactions with environmentally relevant bacteria under representative conditions is necessary to enable their sustainable manufacture, use, and disposal. Previous nanotoxicology research based on planktonic growth has not adequately explored biofilms, which serve as the predominant mode of bacterial growth in natural and engineered environments. Copper nanoparticle (Cu-NP) impacts on biofilms were compared with respective planktonic cultures of the ammonium-oxidizing Nitrosomonas europaea, nitrogen-fixing Azotobacter vinelandii, and denitrifying Paracoccus denitrificans using a suite of independent toxicity diagnostics. Median inhibitory concentration (IC50) values derived from adenosine triphosphate (ATP) for Cu-NPs were lower in N. europaea biofilms (19.6 ± 15.3 mg/L) than in planktonic cells (49.0 ± 8.0 mg/L). However, in absorbance-based growth assays, compared with unexposed controls, N. europaea growth rates in biofilms were twice as resilient to inhibition than those in planktonic cultures. Similarly, relative to unexposed controls, growth rates and yields of P. denitrificans in biofilms exposed to Cu-NPs were 40-fold to 50-fold less inhibited than those in planktonic cells. Physiological evaluation of ammonium oxidation and nitrate reduction suggested that biofilms were also less inhibited by Cu-NPs than planktonic cells. Furthermore, functional gene expression for ammonium oxidation (amoA) and nitrite reduction (nirK) showed lower inhibition by NPs in biofilms relative to planktonic-grown cells. These results suggest that biofilms mitigate NP impacts, and that nitrogen-cycling bacteria in wastewater, wetlands, and soils might be more resilient to NPs than planktonic-based assessments suggest.

The biomechanisms of metal and metal-oxide nanoparticles' interactions with cells.

Humans are increasingly exposed to nanoparticles (NPs) in medicine and in industrial settings, where significant concentrations of NPs are common. However, NP interactions with and effects on biomolecules and organisms have only recently been addressed. Within we review the literature regarding proposed modes of action for metal and metal-oxide NPs, two of the most prevalent types manufactured. Iron-oxide NPs, for instance, are used as tracers for magnetic resonance imaging of oncological tumors and as vehicles for therapeutic drug delivery. Factors and theories that determine the physicochemical and biokinetic behaviors of NPs are discussed, along with the observed toxicological effects of NPs on cells. Key thermodynamic and kinetic models that explain the sources of energy transfer from NPs to biological targets are summarized, in addition to quantitative structural activity relationship (QSAR) modeling efforts. Future challenges for nanotoxicological research are discussed. We conclude that NP studies based on cell culture are often inconsistent and underestimate the toxicity of NPs. Thus, the effect of NPs needs to be examined in whole animal systems.

From science to policy.

A recent conference on the environmental effects of nanoparticles leaves Chris Toumey reflecting on the difficulties of carrying out nanotoxicology research that can be used to develop informed environmental regulation.

Ecotoxicity of silver nanomaterials in the aquatic environment: A review of literature and gaps in nano-toxicological research

There has been extensive growth in nanoscale technology in the last few decades to such a degree that nanomaterials (NMs) have become a constituent in a wide range of commercial and domestic products. With NMs already in use in several consumer products, concerns have emerged regarding their potential adverse environmental impacts. Although research has been undertaken in order to minimise the gaps in our understanding of NMs in the environment, little is known about their bioavailability and toxicity in the aquatic environment. Nano-toxicology is defined as the study of the toxicity of nanomaterials. Nano-toxicology studies remain poorly and unevenly distributed. To date most of the research undertaken has been restricted to a narrow range of test species such as daphnids. Crabs are bio-indicators that can be used for toxicological research on NMs since they occupy a significant position in the aquatic food chain. In addition, they are often used in conventional ecotoxicological studies due to their high sensitivity to environmental stressors and are abundantly available. Because they are benthic organisms they are prone to contaminant uptake and bioaccumulation. To our knowledge the crab has never been used in nano-toxicological studies. In this context, an extensive review on published scientific literature on the ecotoxicity of silver NPs (AgNPs) on aquatic organisms was conducted. Some of the most common biomarkers used in ecotoxicological studies are described. Emphasis is placed on the use of biomarker responses in crabs as monitoring tools, as well as on its limitations. Additionally, the gaps in nano-toxicological research and recommendations for future research initiatives are addressed.

Comparison of TiO2 nanoparticle and graphene–TiO2 nanoparticle composite phototoxicity to Daphnia magna and Oryzias latipes

With a dramatic rise in complexity, needs of nanotoxicology research go beyond simple forms of nanomaterials. This study compared the phototoxicity of nano-TiO2 and graphene–TiO2 nanocomposite (GNP). GNP was synthesized based on a hydrothermal method, which simultaneously performed the reduction of graphene oxide and nano-TiO2 loading. A series of acute toxicity tests of nano-TiO2, graphene and GNP was performed on two aquatic organisms, Daphnia magna and Oryzias latipes. Fast and substantial agglomeration and sedimentation of nanoparticles in test media and surface attachment of nano-TiO2 and GNP on D. magna surface was observed. Similar phototoxicity of nano-TiO2 and GNP for both species existed, though compared with nano-TiO2, GNP had a 2.3-fold increase in visible light photocatalytic ROS generation. In summary, this study demonstrated the significance of illumination spectrum, particle behavior, and species sensitivity on nanophototoxicity, and the needs for research on increasingly sophisticated functional materials.

Analysis of the CSF-samples from the university hospital of Freiburg – Role of lumbar puncture in psychiatry

Concerns about the safety of engineered nanomaterials have not yet been addressed in a systematic way, despite many years of nanotoxicology research. Here we present a computational approach that allows predictions of nanomaterial reactivity as an indicator for toxicity; the approach is powerful, as it is based on fundamental structural criteria, but we also demonstrate that predictions from the simulations fit well with experimentally observed nanoparticle behaviour. Using molecular dynamic simulations, the study predicts surface structures and energetics of silver nanoparticles (AgNPs), which enable an assessment of the impact of water molecules on the surface transformation of AgNPs; the latter controls their behaviour in aqueous media and ultimately their transport, fate, and toxicity. The work shows that size exerts an important control on reactivity and likely also toxicity, a concept proposed at the start of the nanotoxicology debate, but never demonstrated at the smaller end of the nanoscale, or at a systematically resolved range of sizes. A key observation is that experimentally imperceptible differences in size may stabilise structures with hugely different reactivities. We build our framework using AgNPs, but stipulate this can be easily extended to other NP structures and chemistries and expanded to include interactions with biomolecules.

A micro-sized model for the in vivo study of nanoparticle toxicity: what has Caenorhabditis elegans taught us?

Environmental context The ability of the soil nematode Caenorhabditis elegans to withstand a wide range of environmental conditions makes it an idea model for studying the bioavailability and effects of engineered nanomaterials. We critically review what has been learned about the environmental fate of engineered nanoparticles, their effects and their mechanisms of toxicity using this model organism. Future systematic manipulation of nanoparticle properties and environmental variables should elucidate how their interaction influences toxicity and increase the predictive power of nanomaterial toxicity studies. Abstract Recent years have seen a rapid increase in studies of nanoparticle toxicity. These are intended both to reduce the chances of unexpected toxicity to humans or ecosystems, and to inform a predictive framework that would improve the ability to design nanoparticles that are less likely to cause toxicity. Nanotoxicology research has been carried out using a wide range of model systems, including microbes, cells in culture, invertebrates, vertebrates, plants and complex assemblages of species in microcosms and mesocosms. These systems offer different strengths and have also resulted in somewhat different conclusions regarding nanoparticle bioavailability and toxicity. We review the advantages offered by the model organism Caenorhabditis elegans, summarise what has been learned about uptake, distribution and effects of nanoparticles in this organism and compare and contrast these results with those obtained in other organisms, such as daphnids, earthworms, fish and mammalian models.

ChemInform Abstract: Advanced Nuclear Analytical and Related Techniques for the Growing Challenges in Nanotoxicology

AbstractReview: 207 refs.

Determining the count median diameter of nanoaerosols by simultaneously measuring their number and lung-deposited surface area concentrations

Due to the increasing use of nanomaterials in research and product development, it is probable that the number of situations of occupational exposure to them is also rising. The same is true for the number of workers. Although current research in nanotoxicology is far from conclusive, it is clear that relying on mass concentration and chemical composition alone is not appropriate in all cases and alternative measurement methods and approaches need to be developed. In this work, we propose a method based on simultaneous size-integrated measurements of two particle concentrations (number and lung-deposited surface area, CNC/NSAM), and on the estimation of the average size of potentially inhaled particles from the combination of these measurements. The proposed method could be part of a measurement strategy that is practical as it would use field-portable, commercially available aerosol instruments. In the absence of instruments providing real-time size-resolved measurements, this original approach can be carried out as considering that the ratio of these concentrations is a monotonous function of particle size. Indeed, the latter function depends only on the geometric standard deviation of airborne particle number size distribution, assumed to be lognormal. Compared to SMPS data for polydisperse aerosols having three chemical natures with count median diameters ranging from 64 to 177 nm, experimental results were obtained with acceptable relative discrepancies of ±30 %. Though the method proposed is less accurate than traditional instruments like SMPS, it can be used for workplace air monitoring or as a screening tool to detect the presence of airborne nanoparticles.

TEM analysis as a tool for toxicological assessment of occupational exposure to airborne nanoparticles from welding

Welding is the principal industrial process used for joining metals. However, it can produce dangerous fumes that may be hazardous to the welder’s health and it is estimated that, presently, 1-2% of workers from different professional backgrounds (which accounts for more than 3 million persons) are subjected to welding fume and gas action. With the advent of new types of welding procedures and consumables, the number of welders exposed to welding fumes is growing constantly in spite of the mechanization and automation of the processes. Simultaneously, the number of publications on epidemiologic studies and the devices for welders’ protection is also increasing. Apart from that, the influence of very ultrafine particulate, lying in the nanoparticles range, on human health has been pointed to be of much concern as airborne nanoparticles are resulting both from nanotechnologies processes and also from macroscopic common industrial processes such as welding. In fact, nanotoxicological research is still in its infancy and the issuing and implementation of standards for appropriate safety control systems can still take several years. Yet, the advanced understanding of toxicological phenomena on the nanometre scale is largely dependent on technological innovations and scientific results stemming from enhanced R&D. Meanwhile, the industry has to adopt proactive risk management strategies in order to provide a safe working environment for their staff, clients and customers, and obtain products without posing health threats at any point of their lifecycle. Understanding the relationship of airborne nano sized particulate and human health, under different environmental conditions is of great importance for improving exposure estimates and for developing efficient control strategies to reduce human exposure and health risk and for establishing, evaluating and improving regulations and legislation both on air quality, airborne emissions and the incorporation of nano sized materials in other products and commodities.Mass measurement methods are not sufficiently sensitive for airborne nanoparticles and are not sensitive toward the specific health relevant properties of nanoparticles. The most sensitive concentration measured in this particle range (> 100 nm diameter) is the number concentration. In fact, surface area is a relevant metric for nanoparticles, as most of the processes in the human body environment take place via the particle surface, which is increasing significantly with decreasing particle size in the nanometer size range for the same amount of mass. In order to perform the toxicological assessment of welding processes a Nanoparticle Surface Area Monitor, TSI, Model 3550, based on diffusion charging (measuring the electrostatic charge on a sampled aerosol, mainly composed of nanoparticles) was used for monitoring the emission of nanoparticles resulting from several welding processes. This equipment indicates the human lung-deposited surface area of particles expressed as square micrometers per cubic centimeter of air (µm2/cm3). Although this instrument is very precise and its use has been validated for this purpose, the definite presence of nanoparticles in welding fume has to be complemented by microscopy techniques such as transmission electron microscopy (TEM), which has proved very helpful in order to establish the size, shape and aggregation habit of sampled aerosols, as well as energy dispersive X-ray spectroscopy (EDS) for performing the chemical analysis of collected nanoparticles. Figure 1 shows the aspect of aggregates of particles, in the nano size range, collected from welding fume during shielded metal arc welding (SMAW) of carbon steel and friction stir welding (FSW) of aluminium alloys, respectively. As expected in arc welding aggregates of larger dimensions are produced in more roundish shaped particles while in FSW these are finer. Chemical analysis determined by EDS showed that the emitted nanoparticles of SMAW are mostly resulting from burning of electrode coating and less from its core. Therefore, in order to reduce particulate emissions, special care has to be paid to the chemical composition of the electrodes coating.The work was supported by the Portuguese Science Foundation through PEst-OE/EQB/LA0023/2011, PEst-OE/EME/UI0667/2011 and PEst-OE/CTM-UI0084/2011 and grants.

Comparison of Toxicity and Deposition of Nano-Sized Carbon Black Aerosol Prepared With or Without Dispersing Sonication

Nanotoxicological research has shown toxicity of nanomaterials to be inversely related to particle size. However, the contribution of agglomeration to the toxicity of nanomaterials has not been sufficiently studied, although it is known that agglomeration is associated with increased nanomaterial size. In this study, we prepared aerosols of nano-sized carbon black by 2 different ways to verify the effects of agglomeration on the toxicity and deposition of nano-sized carbon black. The 2 methods of preparation included the carbon black dispersion method that facilitated clustering without sonication and the carbon black dispersion method involving sonication to achieve scattering and deagglomeration. Male Sprague-Dawley rats were exposed to carbon black aerosols 6 hr a day for 3 days or for 2 weeks. The median mass aerodynamic diameter of carbon black aerosols averaged 2.08 μm (for aerosol prepared without sonication; group N) and 1.79 μm (for aerosol prepared without sonication; group S). The average concentration of carbon black during the exposure period for group N and group S was 13.08 ± 3.18 mg/m3 and 13.67 ± 3.54 mg/ m3, respectively, in the 3-day experiment. The average concentration during the 2-week experiment was 9.83 ± 3.42 mg/m3 and 9.08 ± 4.49 mg/m3 for group N and group S, respectively. The amount of carbon black deposition in the lungs was significantly higher in group S than in group N in both 3-day and 2-week experiments. The number of total cells, macrophages and polymorphonuclear leukocytes in the bronchoalveolar lavage (BAL) fluid, and the number of total white blood cells and neutrophils in the blood in the 2- week experiment were significantly higher in group S than in normal control. However, differences were not found in the inflammatory cytokine levels (IL-1β, TNF-α, IL-6, etc.) and protein indicators of cell damage (albumin and lactate dehydrogenase) in the BAL fluid of both group N and group S as compared to the normal control. In conclusion, carbon black aerosol generated by sonication possesses smaller nanoparticles that are deposited to a greater extent in the lungs than is aerosol formulated without sonication. Additionally, rats were narrowly more affected when exposed to carbon black aerosol generated by sonication as compared to that produced without sonication.

ECSIN's methodological approach for hazard evaluation of engineered nanomaterials

The increasing production volumes and commercialization of engineered nanomaterials (ENM), together with data on their higher biological reactivity when compared to bulk counterpart and ability to cross biological barriers, have caused concerns about their potential impacts on the health and safety of both humans and the environment. A multidisciplinary component of the scientific community has been called to evaluate the real risks associated with the use of products containing ENM, and is today in the process of developing specific definitions and testing strategies for nanomaterials. At ECSIN we are developing an integrated multidisciplinary methodological approach for the evaluation of the biological effects of ENM on the environment and human health. While our testing strategy agrees with the most widely advanced line of work at the European level, the choice of methods and optimization of protocols is made with an extended treatment of details. Our attention to the methodological and technical details is based on the acknowledgment that the innovative characteristics of matter at the nano-size range may influence the existing testing methods in a partially unpredictable manner, an aspect which is frequently recognized at the discussion level but oftentimes disregarded at the laboratory bench level. This work outlines the most important steps of our testing approach. In particular, each step will be briefly discussed in terms of potential technical and methodological pitfalls that we have encountered, and which are often ignored in nanotoxicology research. The final aim is to draw attention to the need of preliminary studies in developing reliable tests, a crucial aspect to confirm the suitability of the chosen analytical and toxicological methods to be used for the specific tested nanoparticle, and to express the idea that in nanotoxicology,"devil is in the detail".

Whole-Cell Analysis of Low-Density Lipoprotein Uptake by Macrophages Using STEM Tomography

Nanoparticles of heavy materials such as gold can be used as markers in quantitative electron microscopic studies of protein distributions in cells with nanometer spatial resolution. Studying nanoparticles within the context of cells is also relevant for nanotoxicological research. Here, we report a method to quantify the locations and the number of nanoparticles, and of clusters of nanoparticles inside whole eukaryotic cells in three dimensions using scanning transmission electron microscopy (STEM) tomography. Whole-mount fixed cellular samples were prepared, avoiding sectioning or slicing. The level of membrane staining was kept much lower than is common practice in transmission electron microscopy (TEM), such that the nanoparticles could be detected throughout the entire cellular thickness. Tilt-series were recorded with a limited tilt-range of 80° thereby preventing excessive beam broadening occurring at higher tilt angles. The 3D locations of the nanoparticles were nevertheless determined with high precision using computation. The obtained information differed from that obtained with conventional TEM tomography data since the nanoparticles were highlighted while only faint contrast was obtained on the cellular material. Similar as in fluorescence microscopy, a particular set of labels can be studied. This method was applied to study the fate of sequentially up-taken low-density lipoprotein (LDL) conjugated to gold nanoparticles in macrophages. Analysis of a 3D reconstruction revealed that newly up-taken LDL-gold was delivered to lysosomes containing previously up-taken LDL-gold thereby forming onion-like clusters.

Bridge over troubled waters: understanding the synthetic and biological identities of engineered nanomaterials

Engineered nanomaterials offer exciting opportunities for 'smart' drug delivery and in vivo imaging of disease processes, as well as in regenerative medicine. The ability to manipulate matter at the nanoscale enables many new properties that are both desirable and exploitable, but the same properties could also give rise to unexpected toxicities that may adversely affect human health. Understanding the physicochemical properties that drive toxicological outcomes is a formidable challenge as it is not trivial to separate and, hence, to pinpoint individual material characteristics of nanomaterials. In addition, nanomaterials that interact with biological systems are likely to acquire a surface corona of biomolecules that may dictate their biological behavior. Indeed, we propose that it is the combination of material-intrinsic properties (the 'synthetic identity') and context-dependent properties determined, in part, by the bio-corona of a given biological compartment (the 'biological identity') that will determine the interactions of engineered nanomaterials with cells and tissues and subsequent outcomes. The delineation of these entwined 'identities' of engineered nanomaterials constitutes the bridge between nanotoxicological research and nanomedicine.