Metabolomics-based analysis in Daphnia magna after exposure to low environmental concentrations of polystyrene nanoparticles

Larger plastic pieces break down into micro- and eventually nano-sized plastics. This makes nanoplastics ubiquitous in the environment, giving rise to great concern for its effect on biota. Many studies use polystyrene nanoparticles (PS-NPs) as a model for nanoplastics, showing a negative impact on various organisms, but the molecular effects are yet not fully explored. Here we applied 1H nuclear magnetic resonance (NMR) metabolomics to characterize the metabolic changes in Daphnia magna during long-term (37 days) exposure to low concentrations of positively and negatively charged (aminated and carboxylated) PS-NPs. We show that exposure to PS-NPs at concentrations down to 3.2 μg L−1 affected amino acid metabolism and the bacterial metabolite isopropanol in D. magna. These effects were largely independent of particle concentration and surface charge. The results highlight the importance of (1) performing chronic exposures under low concentrations and (2) further investigation of particles with different surface charges

Food Chain Transport of Nanoparticles Affects Behaviour and Fat Metabolism in Fish

Nano-sized (10−9–10−7 m) particles offer many technical and biomedical advances over the bulk material. The use of nanoparticles in cosmetics, detergents, food and other commercial products is rapidly increasing despite little knowledge of their effect on organism metabolism. We show here that commercially manufactured polystyrene nanoparticles, transported through an aquatic food chain from algae, through zooplankton to fish, affect lipid metabolism and behaviour of the top consumer. At least three independent metabolic parameters differed between control and test fish: the weight loss, the triglycerides∶cholesterol ratio in blood serum, and the distribution of cholesterol between muscle and liver. Moreover, we demonstrate that nanoparticles bind to apolipoprotein A-I in fish serum in-vitro, thereby restraining them from properly utilising their fat reserves if absorbed through ingestion. In addition to the metabolic effects, we show that consumption of nanoparticle-containing zooplankton affects the feeding behaviour of the fish. The time it took the fish to consume 95% of the food presented to them was more than doubled for nanoparticle-exposed compared to control fish. Since many nano-sized products will, through the sewage system, end up in freshwater and marine habitats, our study provides a potential bioassay for testing new nano-sized material before manufacturing. In conclusion, our study shows that from knowledge of the molecular composition of the protein corona around nanoparticles it is possible to make a testable molecular hypothesis and bioassay of the potential biological risks of a defined nanoparticle at the organism and ecosystem level

Adsorption of bio-organic eco-corona molecules reduces the toxic response to metallic nanoparticles in <i>Daphnia magna</i>

As the use of engineered nanomaterials increases, so does the risk of them spreading to natural ecosystems. Hitherto, knowledge regarding the toxic properties of nanoparticles (NP’s) and their potential interactions with natural bio-organic molecules adsorbed to them, and thereby forming surface coronas, is limited. However, we show here that the toxic effect of NPs of tungsten carbide cobalt (WC–Co) and cobalt (Co) on the crustacean Daphnia magna is postponed in the presence of natural biological degradation products (eco-corona biomolecules). For Daphnia exposed to WC–Co NPs the survival time increased with 20–25% and for Co NPs with 30–47% after mixing the particles with a solution of eco-corona biomolecules before exposure. This suggests that an eco-corona, composed of biomolecules always present in natural ecosystems, reduces the toxic potency of both studied NPs. Further, the eco-coronas did not affect the particle uptake, suggesting that the reduction in toxicity was related to the particle-organism interaction after eco-corona formation. In a broader context, this implies that although the increasing use and production of NPs may constitute a novel, global environmental threat, the acute toxicity and long-term effects of some NPs will, at least under certain conditions, be reduced as they enter natural ecosystems

Biocompatibility of mannan nanogel : safe interaction with plasma proteins

BACKGROUND: Self-assembled mannan nanogels are designed to provide a therapeutic or vaccine delivery platform based on the bioactive properties of mannan to target mannose receptor expressed on the surface of antigen-presenting cells, combined with the performance of nanogels as carriers of biologically active agents. METHODS: Proteins in the corona around mannan nanogel formed in human plasma were identified by mass spectrometry after size exclusion chromatography or centrifugation followed by sodium dodecyl sulfate polyacrylamide gel electrophoresis. Structural changes and time dependent binding of human apolipoprotein A-I (apoA-I) and human serum albumin (HSA) to mannan nanogel were studied using intrinsic tryptophan fluorescence and circular dichroism spectroscopy. The mannan nanogel effect on blood coagulation and fibrillation of Alzheimer's disease-associated amyloid β peptide and hemodialysis-associated amyloidosis β2 microglobulin was evaluated using thrombin generation assay or thioflavin T fluorescence assay, respectively. RESULTS: The protein corona around mannan nanogel is formed through a slow process, is quite specific comprising apolipoproteins B-100, A-I and E and HSA, evolves over time, and the equilibrium is reached after hours to days. Structural changes and time dependent binding of apoA-I and HSA to mannan nanogel are minor. The mannan nanogel does not affect blood coagulation and retards the fibril formation. CONCLUSIONS: Mannan nanogel has a high biosafety and biocompatibility, which is mandatory for nanomaterials to be used in biomedical applications. GENERAL SIGNIFICANCE: Our research provides a molecular approach to evaluate the safety aspects of nanomaterials, which is of general concern in society and science.The authors thank the financial support by International Iberian Nanotechnology Laboratory (INL), Fundacao para a Ciencia e a Tecnologia (FCT, Portugal), through PTDC, European Science Foundation (ESF) for the activity entitled 'Mapping the detailed composition of Surface-Absorbed Protein Layers on Biomaterials and Nanoparticles', the Crafoord Foundation, and Lund and Nano Vaccine Center, Denmark. The NIPAM coated gold particle is a kind gift from Colloidal Chemistry Group from Vigo University, Spain

Rapid and facile purification of apolipoprotein A-I from human plasma using thermoresponsive nanoparticles

Nanoparticles can be used to purify proteins from plasma. We report here the purification of apolipoprotein A-I (apoA-I) with high specificity from human plasma using copolymeric nanoparticles. We present an optimized protocol using 50:50 NiPAM:BAM copolymer nanoparticles with thermo-responsive properties as an affinity resin. Repeated pelleting and washing of nanoparticle-captured apoA-I is achieved through temperature cycling. The protein is then eluted using urea followed by an ion exchange step for protein concentration and depletion of nanoparticle

Modeling the Time Evolution of the Nanoparticle-Protein Corona in a Body Fluid

Background: Nanoparticles in contact with biological fluids interact with proteins and other biomolecules, thus forming a dynamic corona whose composition varies over time due to continuous protein association and dissociation events. Eventually equilibrium is reached, at which point the continued exchange will not affect the composition of the corona. Results: We developed a simple and effective dynamic model of the nanoparticle protein corona in a body fluid, namely human plasma. The model predicts the time evolution and equilibrium composition of the corona based on affinities, stoichiometries and rate constants. An application to the interaction of human serum albumin, high density lipoprotein (HDL) and fibrinogen with 70 nm N-iso-propylacrylamide/N-tert-butylacrylamide copolymer nanoparticles is presented, including novel experimental data for HDL. Conclusions: The simple model presented here can easily be modified to mimic the interaction of the nanoparticle protein corona with a novel biological fluid or compartment once new data will be available, thus opening novel applications in nanotoxicity and nanomedicine

Autocatalytic amplification of Alzheimer-associated Aβ42 peptide aggregation in human cerebrospinal fluid

Funder: Knut och Alice Wallenbergs Stiftelse (Knut and Alice Wallenberg Foundation); doi: https://doi.org/10.13039/501100004063Funder: Alzheimerfonden; doi: https://doi.org/10.13039/501100008599Abstract: Alzheimer’s disease is linked to amyloid β (Aβ) peptide aggregation in the brain, and a detailed understanding of the molecular mechanism of Aβ aggregation may lead to improved diagnostics and therapeutics. While previous studies have been performed in pure buffer, we approach the mechanism in vivo using cerebrospinal fluid (CSF). We investigated the aggregation mechanism of Aβ42 in human CSF through kinetic experiments at several Aβ42 monomer concentrations (0.8–10 µM). The data were subjected to global kinetic analysis and found consistent with an aggregation mechanism involving secondary nucleation of monomers on the fibril surface. A mechanism only including primary nucleation was ruled out. We find that the aggregation process is composed of the same microscopic steps in CSF as in pure buffer, but the rate constant of secondary nucleation is decreased. Most importantly, the autocatalytic amplification of aggregate number through catalysis on the fibril surface is prevalent also in CSF