Particles and fibres affect human health as a function of their properties such as chemical composition, size and shape but also depending on complex interactions in an organism that occur at various ...levels between particle uptake and target organ responses. While particulate pollution is one of the leading contributors to the global burden of disease, particles are also increasingly used for medical purposes. Over the past decades we have gained considerable experience in how particle properties and particle-bio interactions are linked to human health. This insight is useful for improved risk management in the case of unwanted health effects but also for developing novel medical therapies. The concepts that help us better understand particles' and fibres' risks include the fate of particles in the body; exposure, dosimetry and dose-metrics and the 5 Bs: bioavailability, biopersistence, bioprocessing, biomodification and bioclearance of (nano)particles. This includes the role of the biomolecule corona, immunity and systemic responses, non-specific effects in the lungs and other body parts, particle effects and the developing body, and the link from the natural environment to human health. The importance of these different concepts for the human health risk depends not only on the properties of the particles and fibres, but is also strongly influenced by production, use and disposal scenarios.
Lessons learned from the past can prove helpful for the future of the field, notably for understanding novel particles and fibres and for defining appropriate risk management and governance approaches.
Nanotechnology is identified as a key enabling technology due to its potential to contribute to economic growth and societal well-being across industrial sectors. Sustainable nanotechnology requires ...a scientifically based and proportionate risk governance structure to support innovation, including a robust framework for environmental risk assessment (ERA) that ideally builds on methods established for conventional chemicals to ensure alignment and avoid duplication. Exposure assessment developed as a tiered approach is equally beneficial to nano-specific ERA as for other classes of chemicals. Here we present the developing knowledge, practical considerations and key principles need to support exposure assessment for engineered nanomaterials for regulatory and research applications.
Abstract Nanoparticles are of an appropriate size to interact with cells, and are likely to use a range of cellular machinery for internalisation and trafficking to various sub-cellular compartments. ...It is now understood that once in contact with biological fluids, the nanoparticle surface gets covered by a highly specific layer of proteins, forming the nanoparticle protein corona. This protein layer is stable for times longer than the typical time scale of nanoparticle import, and thus can impact on particle uptake and trafficking inside the cells. In this work, the effect of the corona composition on nanoparticle uptake has been investigated, by studying the impact of serum heat inactivation and complement depletion on the load of nanoparticles accumulated inside the cell. For the same material and nanoparticle size, cellular uptake was found to be significantly different when the nanoparticles were dispersed in medium where the serum was heat inactivated or not heat inactivated, even for non-specialized cells, suggesting that different sera can lead to different nanoparticle doses. The fact that uptake was correlated with the amount of protein bound into the nanoparticle corona suggests the need for commonly agreed dispersion protocols for in vitro nanoparticle–cell studies.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Previous studies have shown that the toxicity of graphene nanomaterials (GNMs) to bacteria are related to the surface functionalization, however, the involved mechanisms are not fully understood. The ...present study aims to explore the toxic mechanisms of differentially functionalized GNMs to bacteria from the aspects of physical interaction, oxidative damage and cell autolysis. Three basic functionalization of GNMs including carboxylation (G-COOH), hydroxylation (G-OH) and amination (G-NH2) were studied. G-COOH (66% viability vs CT group) and G-OH (54%) graphene showed higher toxicity to E. coli than G-NH2 (96%) within 3 h at a concentration of 50 mg/L. The three materials showed distinct physical interaction modes with bacterial cells. G-COOH and G-OH contact with cell membrane via their sharp edges thus causing more damage than G-NH2 which covered the bacteria attaching along the basal plane. The three GNMs showed similar radical generation capacities, thus the direct generation of radicals is not the mechanism causing the toxicity. Instead, the GNMs can oxidize the cellular antioxidant glutathione (GSH) thereby causing oxidative damage. The oxidative capacity follows the order: G-COOH > G-OH > G-NH2, which correlated with the antibacterial activity. Cell autolysis, the degradation of cell wall component peptidoglycan, was found to be a new mechanism inducing the death of bacteria. G-COOH and G-OH caused more cell autolysis than G-NH2, which accounts partially for the different toxicity of the three GNMs. The findings provide significant insights into the mechanism of GNMs toxicity to bacteria for not only the risk assessment of GNMs but also the design of graphene based antibacterial materials.
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•G-COOH and G-OH showed higher toxicity to bacteria than G-NH2.•The three GNMs showed distinct physical interaction modes with bacterial cells.•The three GNMs showed different oxidative potential thereby causing different oxidative damage.•GNMs-induced autolysis is a new mechanism for the GNM toxicity to bacteria.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Charged nanoparticles can alter the local physical properties of lipid membranes, which could shed new light on the interactions between living cells and nanomaterials.
Due to their small size, nanoparticles have distinct properties compared with the bulk form of the same materials. These properties are rapidly revolutionizing many areas of medicine and technology. ...Despite the remarkable speed of development of nanoscience, relatively little is known about the interaction of nanoscale objects with living systems. In a biological fluid, proteins associate with nanoparticles, and the amount and presentation of the proteins on the surface of the particles leads to an in vivo response. Proteins compete for the nanoparticle "surface," leading to a protein "corona" that largely defines the biological identity of the particle. Thus, knowledge of rates, affinities, and stoichiometries of protein association with, and dissociation from, nanoparticles is important for understanding the nature of the particle surface seen by the functional machinery of cells. Here we develop approaches to study these parameters and apply them to plasma and simple model systems, albumin and fibrinogen. A series of copolymer nanoparticles are used with variation of size and composition (hydrophobicity). We show that isothermal titration calorimetry is suitable for studying the affinity and stoichiometry of protein binding to nanoparticles. We determine the rates of protein association and dissociation using surface plasmon resonance technology with nanoparticles that are thiol-linked to gold, and through size exclusion chromatography of protein-nanoparticle mixtures. This method is less perturbing than centrifugation, and is developed into a systematic methodology to isolate nanoparticle-associated proteins. The kinetic and equilibrium binding properties depend on protein identity as well as particle surface characteristics and size.
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BFBNIB, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
The major aim of our current work is to develop a deep understanding of biological effects of nanoparticles and how these effects are mediated by proteins that are adsorbed on the nanoparticles under ...different biological circumstances. Due to their small size, nanoparticles have distinct properties compared to the bulk form of the same materials, and these properties are rapidly revolutionizing many areas of medicine and technology. However, relatively little is known about the interaction of nanoscale objects with biological systems, as this requires quite different concepts from more established nanoscience. Thus, we have argued that in a biological fluid, proteins associate with nanoparticles, and it is the amount and presentation of the proteins on the surface rather than the particles themselves that are the cause of numerous biological responses. It is this outer layer of proteins that is seen by the biological cells, and leads to their responses. We are developing novel techniques to identify and quantify the proteins that are consistently associated with nanoparticles, as a function of the nanoparticle size, shape, and surface properties, and to correlate the adsorbed protein identities with their association and dissociation rates to and from the nanoparticles. We also seek to understand the degree of conformational change that they undergo upon adsorption to the nanoparticles. In essence, we wish to create “epitope maps” of the protein corona that surrounds nanoparticles in biological solutions, as it is the particle–protein complex that is the biologically active entity.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
This article reviews nanoparticulate-chemotherapeutic systems that have been developed for human therapy, considering the components of the nanoparticles, the therapeutic agents associated with the ...nanoparticles and the clinical indications these therapeutic nanoparticles have been developed for. In this evaluation we have put into perspective the types of nanomaterials and their therapeutic indications. We have reviewed the nanoparticulate-chemotherapeutic systems that have been published, approved and marketed and that are currently in clinical use. We have also analyzed the nanoparticulate-chemotherapeutic systems that are in clinical trials and under preclinical development.
Efficient and machine-readable representations are needed to accurately identify, validate and communicate information of chemical structures. Many such representations have been developed (as, for ...example, the Simplified Molecular-Input Line-Entry System and the IUPAC International Chemical Identifier), each offering advantages specific to various use-cases. Representation of the multi-component structures of nanomaterials (NMs), though, remains out of scope for all the currently available standards, as the nature of NMs sets new challenges on formalizing the encoding of their structure, interactions and environmental parameters. In this work we identify a set of principles that a NM representation should adhere to in order to provide “machine-friendly” encodings of NMs, i.e. encodings that facilitate machine processing and cooperation with nanoinformatics tools. We illustrate our principles by showing how the recently introduced InChI-based NM representation, might be augmented, in principle, to also encode morphology and mixture properties, distributions of properties, and also to capture auxiliary information and allow data reuse.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
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