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The wide prevalence of oxidative stress-induced diseases has led to a growing demand for antioxidant therapeutics worldwide. Nanozyme antioxidants are drawing enormous attention as practical alternatives for conventional antioxidants. The considerable body of research over the last decade and the promising results achieved signify the potential of nanozyme antioxidants to secure a place in the expanding market of antioxidant therapeutics. Nonetheless, there is no report on clinical trials for their further evaluation. Through analyzing in-depth selected papers which have conducted in vivo studies on nanozyme antioxidants, this review aims to pinpoint and discuss possible reasons impeding development of research toward clinical studies and to offer some practical solutions for future studies to bridge the gap between preclinical and clinical stages. "We did not experience these kinds of strange illnesses in the past." Everybody might have heard such a familiar sentence from their grandparents and asked themselves, why? The current paper aims to provide readers with one of the answers: "Oxidative stress", which happens when the body fails to neutralize damage caused by unstable molecules called free radicals. In this paper, the authors present the seriousness of oxidative stress-induced clinical conditions. They discuss one of the promising treatments, nanozyme antioxidants, these are mostly based on nano-sized materials with enzyme-like function, in other words, they can speed up chemical reactions. Despite significant results, nanozyme antioxidants have not been investigated in clinical studies. This paper intends to search for the main reasons for this and suggest possible solutions. © 2021 Future Medicine Ltd.

The immune system contributes to maintaining the body’s functional integrity through its two main functions: recognizing and destroying foreign external agents (invading microorganisms) and identifying and eliminating senescent cells and damaged or abnormal endogenous entities (such as cellular debris or misfolded/degraded proteins). Accordingly, the immune system can detect molecular and cellular structures with a spatial resolution of a few nm, which allows for detecting molecular patterns expressed in a great variety of pathogens, including viral and bacterial proteins and bacterial nucleic acid sequences. Such patterns are also expressed in abnormal cells. In this context, it is expected that nanostructured materials in the size range of proteins, protein aggregates, and viruses with different molecular coatings can engage in a sophisticated interaction with the immune system. Nanoparticles can be recognized or passed undetected by the immune system. Once detected, they can be tolerated or induce defensive (inflammatory) or anti-inflammatory responses. This paper describes the different modes of interaction between nanoparticles, especially inorganic nanoparticles, and the immune system, especially the innate immune system. This perspective should help to propose a set of selection rules for nanosafety-by-design and medical nanoparticle design., This research was funded by the EU Commission H2020 project PANDORA (GA 671881; to D.B., P.I. and V.P.). Additional funds were provided by the EU Commission H2020 project ENDONANO (GA 812661; to P.I. and D.B.), the Italian MIUR InterOmics Flagship projects MEMORAT and MAME (to D.B. and P.I.), the Italian MIUR/PRIN-20173ZECCM (to P.I.), the CAS President’s International Fellowship Programme (PIFI; award 2020VBA0028; to D.B.), Spanish Ministerio de Ciencia, Innovación y Universidades (MCIU) (RTI2018-099965-B-I00, AEI/FEDER, UE), and Generalitat de Catalunya (2017-SGR-1431) (V.P.).

The addition of magnetic nanoparticles to batch anaerobic digestion was first reported in 2014. Afterwards, the number of works dealing with this subject has been increasing year by year. The discovery of the enhancement of anaerobic digestion by adding iron-based nanoparticles has created a multidisciplinary emerging research field. As a consequence, in the last years, great efforts have been made to understand the enhancement mechanisms by which magnetic nanoparticles (NPs) addition enhances the anaerobic digestion process of numerous organic wastes. Some hypotheses point to the dissolution of iron as essential iron for anaerobic digestion development, and the state of oxidation of iron NPs that can reduce organic matter to methane. The evolution and trends of this novel topic are discussed in this manuscript. Perspectives on the needed works on this topic are also presented.

Anthropogenic pollution coming from industrial processes, agricultural practices and consumer products, results in the release of toxic substances into rural and urban environments. Once released, these chemicals migrate through the atmosphere and water, and find their way into matrices such as sediments and groundwaters, thus making large areas potentially uninhabitable. Common pollutants, including heavy metal(loid)s, radionuclides, aliphatic hydrocarbons and halogenated organics, are known to adversely affect physiological systems in animal species. Pollution can be cleaned up using techniques such as coagulation, reverse osmosis, oxidation and biological methods, among others. The use of nanoparticles (NPs) extends the range of available technologies and offers particular benefits, not only by degrading, transforming and immobilizing contaminants, but also by reaching inaccessible areas and promoting biotic degradation. The development of NPs is understandably heralded as an environmentally beneficial technology; however, it is only now that the ecological risks associated with their use are being evaluated. This review presents recent developments in the use of engineered NPs for the in situ remediation of two paramount environmental matrices: soils and groundwaters. Emphasis will be placed on (i) the successful applications of nano-objects for environmental cleanup, (ii) the potential safety implications caused by the challenging requirements of [high reactivity toward pollutants] vs. [none reactivity toward biota], with a thorough view on their transport and evolution in the matrix, and (iii) the perspectives on scientific and regulatory challenges. To this end, the most promising nanomaterials will be considered, including nanoscale zerovalent iron, nano-oxides and carbonaceous materials. The purpose of the present review is to give an overview of the development of nanoremediators since they appeared in the 2000s, from their chemical modifications, mechanism of action and environmental behavior to an understanding of the problematics (technical limitations, economic constraints and institutional precautionary approaches) that will drive their future full-scale applications., This work was supported by the Spanish MINECO (MAT2015-70725-R, ENE2017-85087-C3, CTQ2016-75016-R, AEI/FEDER, UE) and from the Generalitat de Catalunya (2017-SGR-1431, 2017-SGR-327). The authors also acknowledge the HISENTS (685817) Project financed by the European Community under H20202 Capacities Programme. V.F.P. acknowledges financial support by the Spanish MINECO through the Ramon y Cajal program (RYC-2012-10991). The Institut Català de Nanociència i Nanotecnologia (ICN2) is jointly supported by the Severo Ochoa program from the Spanish MINECO (Grant No. SEV-2017-0706) and the CERCA Programme/Generalitat de Catalunya. J.O. acknowledges support from the European Social Fund, the Secretaria d'Universitats i Recerca, Departament d'Empresa i Coneixement of the Generalitat de Catalunya (2020 FI_B1 00141) and the Universitat Autònoma de Barcelona (UAB).

We investigated the role of the gold nanoparticles functionalized with polyvinylpyrrolidone (PVP–AuNPs) on the innate immune response against an acute infection caused by Vibrio anguillarum in an in vitro immunological nonmammalian next-generation model, the sea urchin Paracentrotus lividus. To profile the immunomodulatory function of PVP–AuNPs (0.1 μg mL) in sea urchin immune cells stimulated by Vibrio (10 μg mL) for 3 h, we focused on the baseline immunological state of the donor, and we analysed the topography, cellular metabolism, and expression of human cell surface antigens of the exposed cells, as well as the signalling leading the interaction between PVP–AuNPs and the Vibrio-stimulated cells. PVP–AuNPs are not able to silence the inflammatory signalling (TLR4/p38MAPK/NF-κB signalling) that involves the whole population of P. lividus immune cells exposed to Vibrio. However, our findings emphasise the ability of PVP–AuNPs to stimulate a subset of rare cells (defined here as Group 3) that express CD45 and CD14 antigens on their surface, which are known to be involved in immune cell maturation and macrophage activation in humans. Our evidence on how PVP–AuNPs may stimulate sea urchin immune cells represents an important starting point for planning new research work on the topic., This project has received funding from the European Union’s Horizon 2020 research and innovation program under the Marie Skłodowska-Curie grant agreement (No. 671881).

Well-defined colloidal-stable citrate-stabilized Au/CeO2 hybrid nanocrystals (NCs) with coherent quasi-epitaxial interfaces and unprecedented control of their architectural and morphological characteristics have been synthesized via a novel and straightforward seeded-growth aqueous approach. The synthetic strategy, based on the identification of the experimental conditions under which the heterogeneous nucleation and growth processes of CeO2 onto presynthesized Au are controlled, allows for the fine adjustment of each individual domain in the structure, particularly the size of the Au core (from 5 to 100 nm), the thickness of the CeO2 shell (from 5 to 20 nm), and the growth mode of CeO2 onto Au NCs (from core@shell to heterodimer, clover- and star-like structures). This morphological control is achieved by the rational use of sodium citrate, which plays multiple key roles, as a reducer and stabilizing agent in the preparation of Au NCs, and as a complexing agent of Ce3+ for its controlled oxidation and hydrolysis during the subsequent CeO2 deposition. The resultant Au/CeO2 NCs remain stable and well-dispersed in water, allowing us to study the impact of fine variations of the NC structure on the underlying optical response. This level of morphological control, as well as the ease by which such well-defined nanostructures are produced, opens new opportunities for systematically investigating the interactions between individual components in designing more advanced complex NCs. Remarkably, because no organic solvents are used and no toxic waste is formed during the reaction, the proposed synthesis method can be defined as sustainable, viable, and cost-effective., We acknowledge financial support from the Spanish MINECO (MAT2015-70725-R, ENE2017-85087-C3), MICINN (RTI2018-099965-B-I00), and from the Catalan Agencia de Gestió d’Ajuts Universitaris i de Recerca (AGAUR) (2017-SGR-1431, 2017-SGR-327). Financial support from the HISENTS (685817) Project financed by the European Community under H20202 Capacities Programme is gratefully acknowledged. N.G.B. acknowledges financial support by MINECO through the Ramon y Cajal program (RYC-2012-10991). ICN2 is supported by the Severo Ochoa program from Spanish MINECO (grant no. SEV-2017-0706) and is funded by the CERCA Programme/Generalitat de Catalunya. Part of the present work has been performed in the framework of the Universitat Autonoma de Barcelona Degree and Ph.D. program.

Despite the obvious advantages of gold nanoparticles for biomedical applications, controversial and incomplete toxicological data hamper their widespread use. Here, we present the results from an in vivo toxicity study using gold nanoparticles coated with polyethylene glycol (PEG-AuNPs). The pharmacokinetics and biodistribution of PEG-AuNPs were examined in the rat’s liver, lung, spleen, and kidney after a single i.v. injection (0.7 mg/kg) at different time intervals. PEG-AuNPs had a relatively long blood circulation time and accumulated primarily in the liver and spleen, where they remained for up to 28 days after administration. Increased cytoplasmic vacuolation in hepatocytes 24 h and 7 days after PEG-AuNPs exposure and apoptotic-like cells in white splenic pulp 24 h after administration has been detected, however, 28 days post-exposure were no longer observed. In contrast, at this time point, we identified significant changes in lipid metabolism, altered levels of liver injury markers, and elevated monocyte count, but without marked biological relevance. In blood cells, no DNA damage was present in any of the studied time intervals, with the exception of DNA breakage transiently detected in primary kidney cells 4 h post-injection. Our results indicate that the tissue accumulation of PEG-AuNPs might result in late toxic effects., This paper is supported by European Union’s Horizon 2020 research and innovation program under grant agreement No. 857381, project VISION (Strategies to strengthen scientific excellence and innovation capacity for early diagnosis of gastrointestinal cancers), project HISENTS No. 685817, VEGA grants 2/0055/20, 2/0121/21.

Oxidative stress induced by the overproduction of free radicals or reactive oxygen species (ROS) has been considered as a key pathogenic mechanism contributing to the initiation and progression of injury in liver diseases. Consequently, during the last few years antioxidant substances, such as superoxide dismutase (SOD), resveratrol, colchicine, eugenol, and vitamins E and C have received increasing interest as potential therapeutic agents in chronic liver diseases. These substances have demonstrated their efficacy in equilibrating hepatic ROS metabolism and thereby improving liver functionality. However, many of these agents have not successfully passed the scrutiny of clinical trials for the prevention and treatment of various diseases, mainly due to their unspecificity and consequent uncontrolled side effects, since a minimal level of ROS is needed for normal functioning. Recently, cerium oxide nanoparticles (CeO NPs) have emerged as a new powerful antioxidant agent with therapeutic properties in experimental liver disease. CeO NPs have been reported to act as a ROS and reactive nitrogen species (RNS) scavenger and to have multi-enzyme mimetic activity, including SOD activity (deprotionation of superoxide anion into oxygen and hydrogen peroxide), catalase activity (conversion of hydrogen peroxide into oxygen and water), and peroxidase activity (reducing hydrogen peroxide into hydroxyl radicals). Consequently, the beneficial effects of CeO NPs treatment have been reported in many different medical fields other than hepatology, including neurology, ophthalmology, cardiology, and oncology. Unlike other antioxidants, CeO NPs are only active at pathogenic levels of ROS, being inert and innocuous in healthy cells. In the current article, we review the potential of CeO NPs in several experimental models of liver disease and their safety as a therapeutic agent in humans as well., Researches referred by the authors were funded by Fundació La Marató de TV3 (grant Marató 120930), Dirección General de Investigación Científica y Técnica (SAF15-64126-R and RTI2018-094734-B-C21, PID2019-105502RB, and BES-2017-08023), Agència de Gestió d’Ajuts Universitaris i de Recerca (SGR 2017/2019), and Instituto de Salud Carlos III (FIS PI15-00077 and FIS PI19-00774) co-financed by FEDER, European Union, “A way of making Europe” and the National Natural Science Foundation of China (31950410536). The Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd) is funded by the Instituto de Salud Carlos III.

The interaction between engineered nanoparticles and the bacterial lipopolysaccharide, or endotoxin, is an event that warrants attention. Endotoxin is one of the most potent stimulators of inflammation and immune reactions in human beings, and is a very common contaminant in research labs. In nanotoxicology and nanomedicine, the presence of endotoxin on the nanoparticle surface affects their biological properties leading to misinterpretation of results. This review discusses the importance of detecting the endotoxin contamination on nanoparticles, focusing on the current method of endotoxin detection and their suitability for nanoparticulate materials. Conversely, the capacity of nanoparticles to bind endotoxin can be enhanced by functionalization with endotoxin-capturing molecules, opening the way to the development of novel endotoxin detection assays., The authors were supported by the EU H2020 grants ENDONANO [GA 812661] and PANDORA [GA 671881], the IG grant [21420] of the Associazione Italiana Ricerca sul Cancro (AIRC), the project NeON [ARS01_00769] of the Program PRIN, and the projects CIRO- Campania Infrastructure for Research in Oncology and PLATT of the Programma Operativo Regionale of Regione Campania [POR FERS 2014/2020].

Silver nanoparticles (AgNPs) are important and widely used antimicrobials and nanodrug carriers. The increased use of AgNPs in consumer products has raised concerns about nanosafety; for instance, AgNPs may be inhaled and translocate to the brain via olfactory neural stem cells/progenitors. While the biological effects of nanoparticle size have been widely investigated, there are little data on the effects of particle shape on cellular phenotype. Therefore, here we investigated the interactions between AgNP spheres, rods, cubes, and triangles and human plasma proteins and their effects on the viability of NE-4C neural stem cells. Nanoparticles were synthesized by wet chemistry methods and characterized by UV-vis spectroscopy, dynamic light scattering, zeta potential measurement, transmission electron microscopy, nanoparticle tracking analysis, and differential centrifugal sedimentation. NE-4C cell viability was assessed using the MTT reduction assay, and the cellular uptake of differently shaped nanoparticles was monitored by electron microscopy. All 50 nm (in at least one dimension) AgNPs exerted toxic effects, with rods and cubes displaying greater toxicity than spheres and triangles. These cellular and physicochemical results indicate that edges on the AgNPs increase toxicity, presumably due to enhanced ion dissolution from the edges.

Integrating multiple materials with different functionalities in a single nanostructure enables advances in many scientific and technological applications. However, such highly sophisticated nanomaterials usually require complex synthesis processes that complicate their preparation in a sustainable and industrially feasible manner. Herein, we designed a simple general method to grow a mesoporous silica shell onto any combination of hydrophilic nanoparticle cores. The synthetic strategy, based on the adjustment of the key parameters of the sol-gel process for the silica shell formation, allows for the embedment of single, double, and triple inorganic nanoparticles within the same shell, as well as the size-control of the obtained nanocomposites. No additional interfacial adhesive layer is required on the nanoparticle surfaces for the embedding process. Adopting this approach, electrostatically stabilized, small-sized (from 4 to 15 nm) CeO2, Fe3O4, Gd2O3, NaYF4, Au, and Ag cores were used to test the methodology. The mean diameter of the resulting nanocomposites could be as low as 55 nm, with high monodispersity. These are very feasible sizes for biological intervention, and we further observed increased nanoparticle stability in physiological environments. As a demonstration of their increased activity as a result of this, the antioxidant activity of CeO2 cores was enhanced when in core-shell form. Remarkably, the method is conducted entirely at room temperature, atmospheric conditions, and in aqueous solvent with the use of ethanol as co-solvent. These facile and even "green" synthesis conditions favor scalability and easy preparation of multicomponent nanocomposite libraries with standard laboratory glassware and simple benchtop chemistry, through this sustainable and cost-effective fabrication process., This work was financially supported by the National Natural Science Foundation of China (31950410536 to E.C. and 22005221 to M.Z.), the Wuyi University (2018TP010 to E.C., 2018TP011 and 2020FKZX05 to M.Z., and 2019TD02 to J.P.), Guangdong Science and Technology Department (2019A050512006 to E.C.), the Academy of Finland (309374 to J.M.R.), and the Instituto de Salud Carlos III of Spain (PI19/00774 to G.F-V and G.C.), co-financed by FEDER, European Union, “A way of making Europe”.

This is an open access article distributed under the terms of the Creative Commons Attribution License., [Background]: Many toxicological studies on silica nanoparticles (NPs) have been reported, however, the literature often shows various conclusions concerning the same material. This is mainly due to a lack of sufficient NPs characterization as synthesized as well as in operando. Many characteristics of NPs may be affected by the chemistry of their surroundings and the presence of inorganic and biological moieties. Consequently, understanding the behavior of NPs at the time of toxicological assay may play a crucial role in the interpretation of its results. The present study examines changes in properties of differently functionalized fluorescent 50 nm silica NPs in a variety of environments and assesses their ability to absorb proteins from cell culture medium containing either bovine or human serum. [Methods]: The colloidal stability depending on surface functionalization of NPs, their concentration and time of exposure was investigated in water, standard biological buffers, and cell culture media by dynamic light scattering (DLS), zeta potential measurements and transmission electron microscopy (TEM). Interactions of the particles with biological media were investigated by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) in bovine and human serum, and extracted proteins were assessed using matrix-assisted laser desorption/ionization-time of flight technique (MALDI-TOF). [Results]: It was recognized that all of the studied silica NPs tended to agglomerate after relatively short time in buffers and biological media. The agglomeration depended not only on the NPs functionalization but also on their concentration and the incubation time. Agglomeration was much diminished in a medium containing serum. The protein corona formation depended on time and functionalization of NP, and varied significantly in different types of serum. [Conclusions]: Surface charge, ionic strength and biological molecules alter the properties of silica NPs and potentially affect their biological effects. The NPs surface in bovine serum and in human serum varies significantly, and it changes with incubation time. Consequently, the human serum, rather than the animal serum, should be used while conducting in vitro or in vivo studies concerning humans. Moreover, there is a need to pre-incubate NPs in the serum to control the composition of the bio-nano-composite that would be present in the human body. © 2013 Izak-Nau et al.; licensee BioMed Central Ltd., This study was supported by the EU 7th Framework Programme, Marie Curie Actions, Network for Initial Training NanoTOES (PITN-GA-2010-264506)

Studying the behaviour of nanomaterials after their release into natural water is essential to understand the risk associated to their environmental exposure. In particular, the interaction and adsorption of dissolved organic matter onto nanoparticles strongly influence the behaviour and fate of nanomaterials in natural water systems. We herein study the interaction of Au and Ag nanoparticles and humic acids, the principal component of natural dissolved organic matter. Physicochemical characterization results showed the formation of an organic matter corona, consisting of two layers: a “hard” one, firmly bound to the nanoparticle surface, and a “soft” one, in dynamic equilibrium and, consequently, highly dependent on the media organic matter concentration. The extent of the electro-steric stabilization of the so called environmental corona depends on the size of the supramolecular association of humic acid (which depends on its hydrophilic and lipophilic moieties), the nanoparticle size, the total concentration of organic matter in the media, and the ratio between them. Interestingly, environmental coronas can eventually prevent Ca2+ and Mg2+ induced aggregation at concentrations range present in most of the freshwater bodies. The humic coating formed on top of the Au or control Ag nanoparticles presented a similar profile, but the corrodibility of Ag led to a more natural detachment of the corona. These results were further confirmed by exposing the nanoparticles to a model of natural water and standard mud (LUFA 2.2 dispersion). In the latter case, after several days, nanoparticle sedimentation was observed, which was attributed to interactions with macro organic and inorganic matter (fraction larger than particulate matter)., We acknowledge financial support from the Pandora European Training Network (GA-671881) funded in the framework of H2020 Marie Skłodowska-Curie ITN programme, Spanish MINECO (MAT2015-70725-R), and from the Catalan Agència de Gestió d'Ajuts Universitaris i de Recerca (AGAUR) (2017-SGR-1431). N.G.B. acknowledges financial support by MINECO through the Ramon y Cajal program (RYC-2012- 10991). ICN2 is supported by the Severo Ochoa program from Spanish MINECO (Grant No. SEV-2017-0706) and is funded by the CERCA Programme/Generalitat de Catalunya.

We compared the changes of selected immune parameters of Porcellio scaber to different stressors. The animals were either fed for two weeks with Au nanoparticles (NPs), CeO2 NPs, or Au ions or body‐injected with Au NPs, CeO2 NPs, or lipopolysaccharide endotoxin. Contrary to expec-tations, the feeding experiment showed that both NPs caused a significant increase in the total hae-mocyte count (THC). In contrast, the ion‐positive control resulted in a significantly decreased THC. Additionally, changes in phenoloxidase (PO)‐like activity, haemocyte viability, and nitric oxide (NO) levels seemed to depend on the stressor. Injection experiments also showed stressor‐depend-ant changes in measured parameters, such as CeO2 NPs and lipopolysaccharide endotoxin (LPS), caused more significant responses than Au NPs. These results show that feeding and injection of NPs caused an immune response and that the response differed significantly, depending on the exposure route. We did not expect the response to ingested NPs, due to the low exposure concentrations (100 μg/g dry weight food) and a firm gut epithelia, along with a lack of phagocytosis in the digestive system, which would theoretically prevent NPs from crossing the biological barrier. It remains a challenge for future research to reveal what the physiological and ecological significance is for the organism to sense and respond, via the immune system, to ingested foreign material., This research has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement PANDORA No 671881 (Probing safety of nano-objects by defining immune responses of environmental organisms).

Using Au chloride as precursor, Pt nanocrystals as seeds, ascorbic acid as a reducer, and CTAB as surfactant and complexing agent, extremely long Au nanorods have been grown. The influence of different parameters such as the composition of the seeds, the amount of Pt, or the type of Pt present in solution has been analyzed. These large Au NRs have been exhaustively characterized by (S)TEM, SEM and optical microscopy as well as UV-vis spectroscopy and their morphology correlated with the growth mechanism., We acknowledge financial support from Spanish MICINN MAT2006-13572-C02-02-02. M.V. thanks the Spanish MICINN for the financial support through the fellowship BES- 2007-17164, associated with the project.

The size-controlled synthesis of cationic particles by differential reduction of HAuCl4 precursor in the presence of NaBH4 and 1-aminoundecane-12-thiol (AUT) is reported. The number of seed particles is determined by the fraction of the initially Au precursor reduced by NaBH4 present in the reaction mixture, which are then grown larger by the AUT, acting as both weak reducing agent and stabilizing surfactant. By this methodology, size controlled synthesis is achieved in a two-step one-pot synthesis at room temperature.

A low-cost strategy for the simple and rapid detection of bacterial cells in biological matrixes is presented herein. Escherichia coli and Salmonella typhimurium were chosen as model bacteria for the development of an electrochemical assay based on hollow AuAg nanoshells (NSs). By taking advantage of their electrocatalytic properties for the in situ generation of the electrochemical signal without the need of any other kind of reagent, substrate, or redox enzyme, high sensitivities (down to 102 CFU/mL) were achieved. Moreover, the recognition and discrimination of the model bacterial cells in the sample matrix was possible by relying solely on nonspecific affinity interactions between their cell walls and AuAg NSs surface, avoiding the use of expensive and fragile biological receptor. Compared to traditional, laboratory-based analytical tests available, this assay provides a promising proof-of-concept alternative that allows to obtain good sensitivities and selectivity in very short times in addition to the low cost., This work was carried out within the “Doctorat en Quìmica” PhD programme of Universitat Autònoma de Barcelona, supported by the Spanish MINECO (MAT2015-70725-R) and from the Catalan Agència de Gestió d’Ajuts Universitaris i de Recerca (AGAUR) (2017-SGR-143). Financial support from the HISENTS (685817) Project financed by the European Community under H20202 Capacities Programme is gratefully acknowledged. It was also funded by the CERCA Program/Generalitat de Catalunya. ICN2 acknowledges the support of the Spanish MINECO through the Severo Ochoa Centers of Excellence Program under Grant SEV2201320295.

We report that the immunogenicity of colloidal gold nanoparticles coated with polyvinylpyrrolidone (PVP–AuNPs) in a model organism, the sea urchin Paracentrotus lividus, can function as a proxy for humans for in vitro immunological studies. To profile the immune recognition and interaction from exposure to PVP–AuNPs (1 and 10 μg mL−1), we applied an extensive nano-scale approach, including particle physicochemical characterisation involving immunology, cellular biology, and metabolomics. The interaction between PVP–AuNPs and soluble proteins of the sea urchin physiological coelomic fluid (blood equivalent) results in the formation of a protein “corona” surrounding the NPs from three major proteins that influence the hydrodynamic size and colloidal stability of the particle. At the lower concentration of PVP–AuNPs, the P. lividus phagocytes show a broad metabolic plasticity based on the biosynthesis of metabolites mediating inflammation and phagocytosis. At the higher concentration of PVP–AuNPs, phagocytes activate an immunological response involving Toll-like receptor 4 (TLR4) signalling pathway at 24 hours of exposure. These results emphasise that exposure to PVP–AuNPs drives inflammatory signalling by the phagocytes and the resolution at both the low and high concentrations of the PVP–AuNPs and provides more details regarding the immunogenicity of these NPs., This project has received funding from the European Union’s Horizon 2020 research and innovation program under the Marie Skłodowska-Curie grant agreement [No 671881].

Understanding the modes of interaction between human monocytes/macrophages and engineered nanoparticles is the basis for assessing particle safety, in terms of activation of innate/inflammatory reactions, and their possible exploitation for medical applications. In vitro assessment of nanoparticle-macrophage interaction allows for examining the response of primary human cells, but the conventional 2D cultures do not reproduce the three-dimensional spacing of a tissue and the interaction of macrophages with the extracellular tissue matrix, conditions that shape macrophage recognition capacity and reactivity. Here, we have compared traditional 2D cultures with cultures on a 3D collagen matrix for evaluating the capacity gold nanoparticles to induce monocyte activation and subsequent innate memory in human blood monocytes in comparison to bacterial LPS. Results show that monocytes react to stimuli almost in the same way in 2D and 3D cultures in terms of production of TNFα and IL-6, but that notable differences are found when IL-8 and IL-1Ra are examined, in particular in the recall/memory response of primed cells to a second stimulation, with the 3D cultures showing cell activation and memory effects of nanoparticles better. In addition, the response variations in monocytes/macrophages from different donors point towards a personalized assessment of the nanoparticle effects on macrophage activation., This research was funded by the European Commission FP7 project HUMUNITY (GA 316383), the Horizon 2020 projects PANDORA (GA 671881) and ENDONANO (GA 812661), the Italian MIUR Flagship InterOmics project MEMORAT and the PRIN project 20173ZECCM.

Background Nanoparticle (NPs) functionalization has been shown to affect their cellular toxicity. To study this, differently functionalized silver (Ag) and gold (Au) NPs were synthesised, characterised and tested using lung epithelial cell systems. Methods Monodispersed Ag and Au NPs with a size range of 7 to 10 nm were coated with either sodium citrate or chitosan resulting in surface charges from −50 mV to +70 mV. NP-induced cytotoxicity and oxidative stress were determined using A549 cells, BEAS-2B cells and primary lung epithelial cells (NHBE cells). TEER measurements and immunofluorescence staining of tight junctions were performed to test the growth characteristics of the cells. Cytotoxicity was measured by means of the CellTiter-Blue ® and the lactate dehydrogenase assay and cellular and cell-free reactive oxygen species (ROS) production was measured using the DCFH-DA assay. Results Different growth characteristics were shown in the three cell types used. A549 cells grew into a confluent mono-layer, BEAS-2B cells grew into a multilayer and NHBE cells did not form a confluent layer. A549 cells were least susceptible towards NPs, irrespective of the NP functionalization. Cytotoxicity in BEAS-2B cells increased when exposed to high positive charged (+65-75 mV) Au NPs. The greatest cytotoxicity was observed in NHBE cells, where both Ag and Au NPs with a charge above +40 mV induced cytotoxicity. ROS production was most prominent in A549 cells where Au NPs (+65-75 mV) induced the highest amount of ROS. In addition, cell-free ROS measurements showed a significant increase in ROS production with an increase in chitosan coating. Conclusions Chitosan functionalization of NPs, with resultant high surface charges plays an important role in NP-toxicity. Au NPs, which have been shown to be inert and often non-cytotoxic, can become toxic upon coating with certain charged molecules. Notably, these effects are dependent on the core material of the particle, the cell type used for testing and the growth characteristics of these cell culture model systems. Electronic supplementary material The online version of this article (doi:10.1186/s12951-014-0062-4) contains supplementary material, which is available to authorized users.

Dendritic cells (DCs) shape immune responses by influencing T-cell activation. Thus, they are considered both an interesting model for studying nano-immune interactions and a promising target for nano-based biomedical applications. However, the accentuated ability of nanoparticles (NPs) to interact with biomolecules may have an impact on DC function that poses an unexpected risk of unbalanced immune reactions. Here, we investigated the potential effects of gold nanoparticles (AuNPs) on DC function and the consequences for effector and memory T-cell responses in the presence of the microbial inflammatory stimulus lipopolysaccharide (LPS). Overall, we found that, in the absence of LPS, none of the tested NPs induced a DC response. However, whereas 4-, 8-, and 11 nm AuNPs did not modulate LPS-dependent immune responses, 26 nm AuNPs shifted the phenotype of LPS-activated DCs toward a tolerogenic state, characterized by downregulation of CD86, IL-12 and IL-27, upregulation of ILT3, and induction of class E compartments. Moreover, this DC phenotype was less proficient in promoting Th1 activation and central memory T-cell proliferation. Taken together, these findings support the perception that AuNPs are safe under homeostatic conditions; however, particular care should be taken in patients experiencing a current infection or disorders of the immune system., This study shows that gold nanoparticles promote the differentiation of dendritic cells to a tolerogenic-like phenotype, affecting their ability to induce antibacterial immune responses mediated by Th1 cells and to activate central memory T cells.

In this report we combine the catalytic properties of CeO2 nanoparticles with their transduction ability for photoelectrochemical sensing. This study highlights the usage of CeO2 providing catalytic activity towards H2O2, but only with a limited excitation range in the UV for the construction of a sensing system. In order to improve the photoelectrocatalysis of CeO2 nanoparticles by extending their excitation to visible light, Au/CeO2 core/shell hybrid nanoparticles have been synthesized. The hybrid nanoparticles are fixed on electrodes, allowing for the generation of photocurrents, the direction of which can be controlled by the electrode potential (without bias). The application of the hybrid nanoparticles results in an enhanced photocurrent amplitude under white light illumination as compared to the pure CeO2 nanoparticles. Wavelength-dependent measurements confirm the participation of the Au core in the signal transduction. This can be explained by improved charge carrier generation within the hybrid particles. Thus, by using a plasmonic element the photoelectochemical response of a catalytic nanoparticle (i.e. CeO2) has been spectrally extended. The effect can be exploited for sensorial hydrogen peroxide detection. Here higher photocatalytic current responses have been found for the hybrid particles fixed to gold electrodes although the catalytic reduction has been comparable for both types of nanoparticles. Thus, it can be demonstrated that Au/CeO2 core–shell nanoparticles allow the utilization of visible light for photoelectrochemical hydrogen peroxide (H2O2) detection with improved sensitivity under white light illumination or application of such particles with only visible light excitation, which is not possible for pure CeO2. With help of the layer-by-layer (LbL) technique for nanoparticle immobilization, the electrode response can be adjusted and with a 5 layers electrode a low detection limit of about 3 μM H2O2 with a linear detection range up to 2000 μM is obtained., SZ was supported by the Chinese Scholarship Council (CSC). ZY thanks the National Natural Science Foundation of China (Grant No. 61471207 and 61871240). WJP was supported by the Cluster of Excellence ‘Advanced Imaging of Matter’ of the Deutsche Forschungsgemeinschaft (DFG) – EXC 2056 – project ID 390715994. NGB and VP acknowledge financial support from the Spanish Ministerio de Ciencia, Innovación y Universidades (MCIU) (RTI2018-099965-B-I00, AEI/FEDER, UE). N. G. B. acknowledges financial support by MINECO through the Ramon y Cajal program (RYC-2012-10991). ICN2 is supported by the Severo Ochoa program from Spanish MINECO (SEV-2017-0706) and is funded by the CERCA Programme/Generalitat de Catalunya.

Financial support was provided by the Spanish Ministerio de Medio Ambiente y Medio Rural y Marino (Project Exp. 007/RN08/03.1). Altres ajuts: MAPAMA/007/RN08/03.1 This article presents recent developments on the use of inorganic nanoparticles (NPs) for environmental remediation in polluted soil, water and gas. The number of publications on these topics has grown exponentially in recent years, especially those focused on wastewater treatment. Among these topics, removal of metals has become the most popular, although some works relate to the use of nanomaterials for the elimination of nutrients (e.g., nitrogen and some persistent organic pollutants). However, this growth has not been accompanied by knowledge about the behavior of NPs once used and released into the environment. In this article, we also comment upon the current situation with respect to NP toxicology (nanotoxicology). A remarkable number of different toxicology tests has been applied to NPs, often making it very difficult to interpret or to generalize the results. We analyze in detail the bioluminescence, Daphnia magna and other tests, and give some preliminary results obtained in our work.

Surface modifications of highly monodisperse citrate-stabilized gold nanoparticles (AuNPs) with sizes ranging from 3.5 to 150 nm after their exposure to cell culture media supplemented with fetal bovine serum were studied and characterized by the combined use of UV-vis spectroscopy, dynamic light scattering, and zeta potential measurements. In all the tested AuNPs, a dynamic process of protein adsorption was observed, evolving toward the formation of an irreversible hard protein coating known as Protein Corona. Interestingly, the thickness and density of this protein coating were strongly dependent on the particle size, making it possible to identify different transition regimes as the size of the particles increased: (i) NP-protein complexes (or incomplete corona), (ii) the formation of a near-single dense protein corona layer, and (iii) the formation of a multilayer corona. In addition, the different temporal patterns in the evolution of the protein coating came about more quickly for small particles than for the larger ones, further revealing the significant role that size plays in the kinetics of this process. Since the biological identity of the NPs is ultimately determined by the protein corona and different NP-biological interactions take place at different time scales, these results are relevant to biological and toxicological studies.

Human exposure to nano- and microplastics (NMPs) has raised major societal concerns, yet no framework to assess the risks of NMPs for human health exists. A substantial proportion of plastic produced worldwide is not properlydisposed and persists in the environment for decades while degrading. Plastic degradation generates a size continuum of fragments, including nano- and microplastic particles, with numerous associated environmentalpollutants and plastic additives, and microbial communities colonising their surfaces. The ubiquitous presence of NMPs, their availability for uptake by organisms and their potential to act as vectors for toxicants and pathogensrender risk assessment a priority on the political agenda at the global level. We provide a new, fully integrated riskassessment framework tailored to the specificities of NMPs, enabling an assessment of current and future human health risks from NMPs. The framework consists of four novel paradigms to the traditional risk assessmentmethodology. These paradigms deal with techniques in NMP analysis, gaps in empirical data, theoretical and modelling approaches and stakeholder engagement. Within the proposed framework, we propose how we can useresearch experiences gained so far to carry out the different steps of the assessment process, and we define priorities for further research.Keywords: Microplastics, nanoplastics, risk assessment, human health, hazard identification, exposure assessment, hazard characterization, stakeholder engagement, food, air

Financial support was provided by the Spanish Ministerio de Medio Ambiente y Medio Rural y Marino (Project Exp. 007/RN08/03.1). Altres ajuts: MAPAMA/007/RN08/03.1 Growth in production and use of nanoparticles (NPs) will result increased concentrations of these in industrial and urban wastewaters and, consequently, in wastewater-treatment facilities. The effect of this increase on the performance of the wastewater-treatment process has not been studied systematically and including all the microbial communities involved in wastewater treatment. The present work investigates, by using respiration tests and biogas-production analysis, the inhibitory effect of four different commonly used metal oxide (CeO₂ and TiO₂) and zero-valent metal (Ag and Au) nanoparticles on the activity of the most important microbial communities present in a modern wastewater-treatment plant. Specifically, the actions of ordinary heterotrophic organisms, ammonia oxidizing bacteria, and thermophilic and mesophilic anaerobic bacteria were tested in the presence and absence of the nanoparticles. In general, CeO₂ nanoparticles caused the greatest inhibition in biogas production (nearly 100%) and a strong inhibitory action of other biomasses; Ag nanoparticles caused an intermediate inhibition in biogas production (within 33-50%) and a slight inhibition in the action of other biomasses, and Au and TiO₂ nanoparticles caused only slight or no inhibition for all tested biomasses.

Approaches are needed for the tailored assembly of plasmonic building blocks on the surface of substrates to synergistically enhance their properties. Here we demonstrate selective immobilization and assembly of gold nanorods (NRs) on substrates modified and patterned with end-grafted poly(ethylene glycol) (PEG) layers. The ligand exchange from the initial cetyltrimethylammonium bromide to sodium citrate was necessary for the immobilization of gold NRs onto PEG grafted substrates. Linear nanopatterns of PEG were fabricated using electrospun nanofibers as masks in oxygen plasma etching. The selective immobilization of citrate-stabilized gold NRs with a length of ∼50 nm and a width of 20 nm on the nanopatterned PEG layers led to linear and registered arrays of rods. The number of gold NRs per line depended on the width of the patterns and approached 1 when the width of the patterns was comparable to the length of the rods. The confinement of the binding regions led to a ∼3 fold increase in the number of gold NRs immobilized per unit area. The selective and dense immobilization of gold NRs on the nanoscale patterns of PEG resulted in spatially defined and strong surface-enhanced Raman scattering activity enabling detection of molecules at concentrations as low as 1 nM., This work was supported by Research Fund of the Erciyes University (Project Number: FYL-2016-6896). ICN2 is supported by the Severo Ochoa program from Spanish MINECO (Grant No. SEV-2013-0295) and funded by the CERCA Programme/Generalitat de Catalunya.

HIV represents a persistent infection which negatively alters the immune system. New tools to reinvigorate different immune cell populations to impact HIV are needed. Herein, a novel nanotool for the specific enhancement of the natural killer (NK) immune response towards HIV-infected T-cells has been developed. Bispecific Au nanoparticles (BiAb-AuNPs), dually conjugated with IgG anti-HIVgp120 and IgG anti-human CD16 antibodies, were generated by a new controlled, linker-free and cooperative conjugation method promoting the ordered distribution and segregation of antibodies in domains. The cooperatively-adsorbed antibodies fully retained the capabilities to recognize their cognate antigen and were able to significantly enhance cell-to-cell contact between HIV-expressing cells and NK cells. As a consequence, the BiAb-AuNPs triggered a potent cytotoxic response against HIV-infected cells in blood and human tonsil explants. Remarkably, the BiAb-AuNPs were able to significantly reduce latent HIV infection after viral reactivation in a primary cell model of HIV latency. This novel molecularly-targeted strategy using a bispecific nanotool to enhance the immune system represents a new approximation with potential applications beyond HIV., This study was supported by the Spanish Secretariat of Science and Innovation and FEDER funds (grants SAF2015-67334-R and RTI2018-101082-B-I00 [MINECO/FEDER]), American National Institutes of Health (grant R21AI118411 to M.B), an unrestricted research grant from Bristol-Myers Squibb S.A.U (PfC-2015-AI424-564) to M.B, the Spanish “Ministerio de Economía y Competitividad, Instituto de Salud Carlos III” (ISCIII, PI17/01470) to M.G and the Spanish “Ministerio de Economía y Competitividad, Instituto de Salud Carlos III” (ISCIII, PI14/01058) to J.G.P, a research grant from Gilead Sciences (GLD17-00204 and GLD19-00084) to M.B, GeSIDA and the Spanish AIDS network “Red Temática Cooperativa de Investigación en SIDA” (RD16/0025/0007). The Miguel Servet program funded by the Spanish Health Institute Carlos III (CP17/00179) to M.B and J.G.P (CPII15/00014). The “Pla estratègic de recerca i innovació en salut” (PERIS), from the Catalan Government to M.G. The Spanish Secretariat of Science and Innovation Ph.D. fellowship to A.A-G (BES-2016-076382), AGAUR-FI-B-00582 Ph.D. fellowship from the Catalan Government to O.BL, and PIF-UAB Ph.D. fellowship from Universitat Autònoma de Barcelona to R.SL.

Obesity is one of the most important public health problems that is associated with an array of metabolic disorders linked to cardiovascular disease, stroke, type 2 diabetes, and cancer. A sustained therapeutic approach to stop the escalating prevalence of obesity and its associated metabolic comorbidities remains elusive. Herein, we developed a novel nanocomposite based on mesoporous silica coated cerium oxide (CeO2) nanozymes that reduce the circulating levels of fatty acids and remarkably improve the metabolic phenotype in a model of obese Zucker rats five weeks after its administration. Lipidomic and gene expression analyses showed an amelioration of the hyperlipidemia and of the hepatic and adipose metabolic dysregulations, which was associated with a down-regulation of the hepatic PI3K/mTOR/AKT pathway and a reduction of the M1 proinflammatory cytokine TNF-a. In addition, the coating of the CeO2 maximized its cell antioxidant protective effects and minimized non-hepatic biodistribution. The one-pot synthesis method for the nanocomposite fabrication is implemented entirely in aqueous solution, room temperature and open atmosphere conditions, favoring scalability and offering a safe and translatable lipid-lowering and antioxidant nanomedicine to treat metabolic comorbidities associated with obesity. This approach may be further applied to address other metabolic disorders related to hyperlipidemia, low-grade inflammation and oxidative stress., This research was supported by the Instituto de Salud Carlos III (PI19/00774 to G. C. and G. F.-V.), Dirección General de Investigación Científica y Técnica (RTI2018-094734-B-C2 to W. J.), co-financed by FEDER, European Union, “A way of making Europe”, and the Secretaria d'Universitats i Recerca del Departament d'Empresa i Coneixement de la Generalitat de Catalunya (2018_PROD_00187 to W. J.), the National Natural Science Foundation of China (31950410536 to E. C. and 22005221 to M. Z.), the Wuyi University Funding (2018TP010 to E. C., and 2018TP011 and 2020FKZX05 to M. Z.), Guangdong Science and Technology Department (2019A050512006 to E. C.), and the Academy of Finland (309374 to J. M. R.).

Nanoparticles (NPs) show various properties depending on their composition, size, and surface coating, which shape their interactions with biological systems. In particular, NPs have been shown to interact with immune cells, that represent a sensitive surveillance system of external and internal stimuli. In this light, in vitro models represent useful tools for investigating nano-bio-interactions in immune cells of different organisms, including invertebrates. In this work, the effects of selected types of NPs with different core composition, size and functionalization (custom-made PVP-AuNP and commercial nanopolystyrenes PS-NH2 and PS-COOH) were investigated in the hemocytes of the marine bivalve Mytilus galloprovincialis. The role of exposure medium was evaluated using either artificial seawater (ASW) or hemolymph serum (HS). Hemocyte morphology was investigated by scanning electron microscopy (SEM) and different functional parameters (lysosomal membrane stability, phagocytosis, and lysozyme release) were evaluated. The results show distinct morphological and functional changes induced in mussel hemocytes depending on the NP type and exposure medium. Mussel hemocytes may represent a powerful alternative in vitro model for a rapid pre-screening strategy for NPs, whose utilization will contribute to the understanding of the possible impact of environmental exposure to NPs in marine invertebrates.

Microfluidic technology is a valuable tool for realizing more in vitro models capturing cellular and organ level responses for rapid and animal-free risk assessment of new chemicals and drugs. Microfluidic cell-based devices allow high-throughput screening and flexible automation while lowering costs and reagent consumption due to their miniaturization. There is a growing need for faster and animal-free approaches for drug development and safety assessment of chemicals (Registration, Evaluation, Authorisation and Restriction of Chemical Substances, REACH). The work presented describes a microfluidic platform for in vivo-like in vitro cell cultivation. It is equipped with a wafer-based silicon chip including integrated electrodes and a microcavity. A proof-of-concept using different relevant cell models shows its suitability for label-free assessment of cytotoxic effects. A miniaturized microscope within each module monitors cell morphology and proliferation. Electrodes integrated in the microfluidic channels allow the noninvasive monitoring of barrier integrity followed by a label-free assessment of cytotoxic effects. Each microfluidic cell cultivation module can be operated individually or be interconnected in a flexible way. The interconnection of the different modules aims at simulation of the whole-body exposure and response and can contribute to the replacement of animal testing in risk assessment studies in compliance with the 3Rs to replace, reduce, and refine animal experiments., T.K. and Y.K. contributed equally to this work. The authors thank Frank Bauerfeld for system assembly and electrical testing, Werner Haberer for assembly of the microfluidic cartridges, Axel Brenner for the fabrication of the silicon micro cavity chips, Hoffman La Roche for providing the Ro 19-8022, NorGenoTech for providing the Fpg enzyme, and Karen Steenson for proofreading. This research was funded by the European Commission under the Horizon2020 programme (HISENTS, Grant Agreement No. 685817 and VISION, Grant Agreement No. 857381); and by the Norwegian Research Council Norway (RCN) via the European Research Area Network (ERA-NET) EuroNanoMed II project INNOCENT (RCN 271075) and the ERA-NET EuroNanoMed III project Graphene-encapsulated magnetic nanoparticles (RCN 246672/O70). K.K. received Short Term Scientific Mission Grant (ID 42926) under COST Action CA 17140 “Cancer Nanomedicine from the Bench to the Bedside” supported by COST (European Cooperation in Science and Technology). E.E. received funding from the Norwegian Research Council (272412/F40). O.H.M. received funding from the Spanish Ministry of Economy and Competitiveness (SEV-2013-0295-17-3).

(1) In compliance with the 3Rs policy to reduce, refine and replace animal experiments, the development of advanced in vitro models is needed for nanotoxicity assessment. Cells cultivated in 3D resemble organ structures better than 2D cultures. This study aims to compare cytotoxic and genotoxic responses induced by titanium dioxide (TiO2), silver (Ag) and zinc oxide (ZnO) nanoparticles (NPs) in 2D monolayer and 3D spheroid cultures of HepG2 human liver cells. (2) NPs were characterized by electron microscopy, dynamic light scattering, laser Doppler anemometry, UV-vis spectroscopy and mass spectrometry. Cytotoxicity was investigated by the alamarBlue assay and confocal microscopy in HepG2 monolayer and spheroid cultures after 24 h of NP exposure. DNA damage (strand breaks and oxidized base lesions) was measured by the comet assay. (3) Ag-NPs were aggregated at 24 h, and a substantial part of the ZnO-NPs was dissolved in culture medium. Ag-NPs induced stronger cytotoxicity in 2D cultures (EC50 3.8 &micro, g/cm2) than in 3D cultures (EC50 &gt, 30 &micro, g/cm2), and ZnO-NPs induced cytotoxicity to a similar extent in both models (EC50 10.1&ndash, 16.2 &micro, g/cm2). Ag- and ZnO-NPs showed a concentration-dependent genotoxic effect, but the effect was not statistically significant. TiO2-NPs showed no toxicity (EC50 &gt, 75 &micro, g/cm2). (4) This study shows that the HepG2 spheroid model is a promising advanced in vitro model for toxicity assessment of NPs.

In the environment engineered nanoparticles (ENPs) are subject to chemical and physical transformation processes. Thus, to understand their impact, it is important to consider how bioavailability and toxicity are influenced by these “aging” transformations with relation to environmental conditions and ENP properties. Here, two soil bacteria were exposed to Ag ENPs in ISO media (± fulvic acid) and soil pore water extracts with pH 6 and pH 8. The ENPs tested were 49 nm unfunctionalised, citrate stabilised (Ag-citr), 58 nm PVP-coated (Ag-PVP) and 36 nm sulphidised (Ag2S-PVP); AgNO3 was used as a positive control. Exposures were carried out using pristine (unaged) and 24 h aged ENPs, and the 24 h soluble fraction. Overall, toxicity was ranked AgNO3 > Ag-PVP ≥ Ag-citr ≫ Ag2S. Aging of AgNO3, Ag-PVP and Ag-citr in the ISO medium caused little change from unaged exposures and growth inhibition was mainly caused by soluble silver. Added fulvic acid decreased silver toxicity after aging and reduced the contribution of dissolution; as was the case in the soil pore waters where toxicity could not be attributed to ionic silver. Ag2S toxicity to A. globiformis in both ISO variants increased after aging, yet followed the same patterns as the metallic ENPs in the pore waters. For all ENPs pH effects were species dependent. Together this data showed that aging reduced toxicity in media with organic matter and despite soluble silver being the main driver of pristine ENP toxicity in the standard ISO medium, dissolution did not fully explain toxicity in the presence of organic matter., This work was funded by the project GUIDEnano under the 7th Framework Programme of the European Commission (grant agreement no. 6043387), the Natural Environment Research Council Highlight Topic Nanomaterials (grant number: NE/N006224/1), and the project NanoFASE under the EU Horizon 2020 research innovation programme (grant agreement no. 646002).

Engineered nanoparticles (NPs) entering the environment are subject to various transformations that in turn influence how particles are presented to, and taken up by, organisms. To understand the effect of soil properties on the toxicity of nanosilver to Caenorhabditis elegans, toxicity assays were performed in porewater extracts from natural soils with varying organic matter content and pH using 3-8 nm unfunctionalized silver (Ag 3-8Unf), 52-nm polyvinylpyrrolidone (PVP)-coated Ag NPs (Ag 52PVP), and AgNO3 as ionic Ag. Effects on NP agglomeration and stability were investigated using ultraviolet-visible (UV-vis) spectroscopy and asymmetric flow field-flow fractionation (AF4); Ag+ showed greater overall toxicity than nanosilver, with little difference between the NP types. Increasing soil organic matter content significantly decreased the toxicity of Ag 3-8Unf, whereas it increased that of AgNO3 . The toxicity of all Ag treatments significantly decreased with increasing porewater pH. Dissolution of both NPs in the porewater extracts was too low to have contributed to their observed toxic effects. The UV-vis spectroscopy revealed low levels of agglomeration/aggregation independent of soil properties for Ag 3-8Unf, whereas higher organic matter as well as low pH appeared to stabilize Ag 52PVP. Overall, both soil organic matter content and pH affected NP fate as well as toxicity to C. elegans; however, there appears to be no clear connection between the measured particle characteristics and their effect. Environ Toxicol Chem 2018;37:2609-2618. © 2018 SETAC.

Here, we report the synthesis of (multi)-layered zeolitic imidazolate framework (ZIF-8/-67) composite particles via a sequential deconstruction–reconstruction process. We show that this process can be applied to construct ZIF-8-on-ZIF-67 composite particles whose cores are the initially etched particles. In addition, we demonstrate that introduction of functional inorganic nanoparticles (INPs) onto the crystal surface of etched particles does not disrupt ZIF particle reconstruction, opening new avenues for designing (multi)-layered ZIF-on-INP-on-ZIF composite particles comprising more than one class of inorganic nanoparticles. In these latter composites, the location of the inorganic nanoparticles inside each single metal–organic framework particle as well as of their separation at the nanoscale (20 nm) is controlled. Preliminary results show that (multi)-layered ZIF-on-INP-on-ZIF composite particles comprising a good sequence of inorganic nanoparticles can potentially catalyze cascade reactions., This work was supported by the EU FP7 ERC-Co 615954, the Spanish MINECO (projects PN MAT2015-65354-C2-1-R, MAT2015-70725-R, and CTQ2016-77989-P), and the Catalan AGAUR (projects 2014 SGR 80, 2014 SGR 612 and 2014 SGR 862). It was also funded by the CERCA Program/Generalitat de Catalunya. N.G.B. acknowledges financial support by MINECO through the Ramon y Cajal program (RYC-2012-10991). ICN2 acknowledges the support of the Spanish MINECO through the Severo Ochoa Centers of Excellence Program under Grant SEV-2013-0295.

The global economic success of man-made nanoscale materials has led to a higher production rate and diversification of emission sources in the environment. For these reasons, novel nanosafety approaches to assess the environmental impact of engineered nanomaterials are required. While studying the potential toxicity of metal nanoparticles (NPs), we realized that gold nanoparticles (AuNPs) have a growth-promoting rather than a stress-inducing effect. In this study we established stable short-and long-term exposition systems for testing plant responses to NPs. Exposure of plants to moderate concentrations of AuNPs resulted in enhanced growth of the plants with longer primary roots, more and longer lateral roots and increased rosette diameter, and reduced oxidative stress responses elicited by the immune-stimulatory PAMP flg22. Our data did not reveal any detri-mental effects of AuNPs on plants but clearly showed positive effects on growth, presumably by their protective influence on oxidative stress responses. Differential transcriptomics and proteomics analyses revealed that oxidative stress responses are downregulated whereas growth-promoting genes/proteins are upregulated. These omics datasets after AuNP exposure can now be exploited to study the underlying molecular mechanisms of AuNP-induced growth-promotion., This research received funding from the European Union’s Horizon 2020 research and innovation program under the Marie Sklodowska-Curie grant agreement PANDORA, no. 671881.

The interaction of inorganic nanoparticles and many biological fluids often withstands the formation of a Protein Corona enveloping the nanoparticle. This Protein Corona provides the biological identity to the nanoparticle that the immune system will detect. The formation of this Protein Corona depends not only on the composition of the nanoparticle, its size, shape, surface state and exposure time, but also on the type of media, nanoparticle to protein ratio and the presence of ions and other molecular species that interfere in the interaction between proteins and nanoparticles. This has important implications on immune safety, biocompatibility and the use of nanoparticles in medicine.

This is the peer reviewed version of the following article: Rodríguez‐San‐Miguel, D., Yazdi, A., Guillerm, V., Pérez‐Carvajal, J., Puntes, V., Maspoch, D., & Zamora, F. (2017). Confining Functional Nanoparticles into Colloidal Imine‐Based COF Spheres by a Sequential Encapsulation–Crystallization Method. Chemistry–A European Journal, 23(36), 8623-8627, which has been published in final form at https://doi.org/10.1002/chem.201702072. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions, Here, a two-step method is reported that enables imparting new functionalities to covalent organic frameworks (COFs) by nanoparticle confinement. The direct reaction between 1,3,5-tris(4-aminophenyl)benzene and 1,3,5-benzenetricarbaldehyde in the presence of a variety of metallic/metal-oxide nanoparticles resulted in embedding of the nanoparticles in amorphous and non-porous imine-linked polymer organic spheres (NP@a-1). Post-treatment reactions of NP@a-1 with acetic acid under reflux led to crystalline and porous imine-based COF-hybrid spheres (NP@c-1). Interestingly, Au@c-1 and Pd@c-1 were found to be catalytically active, This work was supported by the Spanish MINECO (projects PN MAT2016‐77608‐C3‐1‐P and MAT2015‐65354‐C2‐1‐R), the Catalan AGAUR (project 2014 SGR 80), and the ERC under the EU FP7 (ERC‐Co 615954). V.G. is grateful to the Generalitat de Catalunya for a Beatriu de Pinós fellowship (2014 BP‐B 00155). A.Y. and ICN2 acknowledge the support of the Spanish MINECO through the Severo Ochoa Centers of Excellence Program, under Grant SEV‐2013‐0295

We analyzed the different spectroscopic profiles of nanoparticle hard protein corona formation using two model proteins, albumin and immunoglobulin. When compared to serum, this served for the analysis of the hard protein corona main components. To do that, we employed time-resolved UV-Visible light absorption spectroscopy, dynamic light scattering, and zeta potential measurements during nanoparticle–protein incubation. Under the tested experimental conditions, the expected evolution from a non-stable (soft) to a stable (hard) protein corona was confirmed for serum and albumin. At the same time, immunoglobulin incubation inevitably failed to form a corona and led to nanoparticle aggregation. The formation profiles of the protein corona were similar in the case of albumin and serum, indicating the dominance of albumin coating the nanoparticle surface when exposed to plasma. This was confirmed by mass spectrometry. Chemical digestion of the nanoparticles bearing different protein coronas gave indications of the density of the different protein coatings. Overall, this study of the protein corona by determining the adsorption kinetics finger-print enables the development of precise nanotechnologies avoiding cumbersome processes and delaying proteomics analysis., We acknowledge financial support from the Instituto de Salud Carlos III (AC16/00053 and PI18/00219). EC thanks the National Natural Science Foundation of China through e31950410536.

A modular molecular hybrid colloidal photocatalyst composed of TiO2 nanocrystals (TiO2-NCs) as a light absorber and the molecular complex [Ru(tda)(pypyr)2], Ru-tda, as a water oxidation catalyst precursor both anchored onto single-walled carbon nanotubes (SWCNTs) is described. This colloidal molecular hybrid photocatalyst, labeled as Ru-tda/SWCNT/TiO2-NCs, is a robust material that can be easily prepared and scaled up. At neutral pH, in the presence of 3 sun illumination, the molecular hybrid material Ru-tda/SWCNT/TiO2-NCs is capable of achieving the photocatalytic oxidation of water to dioxygen in the presence of persulfate, giving an unprecedented turnover number of 229., The authors acknowledge financial support from BIST Ignite project SOLHYCAT. N.G.B. and V.P. acknowledge financial support from the Spanish MCIU (RTI2018-099965-B-I00, AEI/FEDER, UE) and Generalitat de Catalunya (2017-SGR-1431). A.L. acknowledges support from MINECO, FEDER, and AGAUR (PID2019-111617RB-I00, 2017-SGR-1631). N.G.B. acknowledges financial support from MINECO through the Ramon y Cajal program (RYC-2012- 10991). M.V. thanks “la Caixa” Foundation for the INPhINIT fellowship program. ICN2 is supported by the Severo Ochoa program from Spanish MINECO (grant no. SEV-2017-0706), and ICN2 and ICIQ are funded by the CERCA Program from Generalitat de Catalunya.

© 2020 by the authors., Innate immune memory is characterized by a modulation in the magnitude with which innate immune cells such as monocytes and macrophages respond to potential dangers, subsequent to previous exposure to the same or unrelated agents. In this study, we have examined the capacity of gold nanoparticles (AuNP), which are already in use for therapeutic and diagnostic purposes, to modulate the innate memory induced by bacterial agents. The induction of innate memory was achieved in vitro by exposing human primary monocytes to bacterial agents (lipopolysaccharide -LPS-, or live Bacille Calmette-Guérin -BCG) in the absence or presence of AuNP. After the primary activation, cells were allowed to return to a resting condition, and eventually re-challenged with LPS. The induction of memory was assessed by comparing the response to the LPS challenge of unprimed cells with that of cells primed with bacterial agents and AuNP. The response to LPS was measured as the production of inflammatory (TNFα, IL-6) and anti-inflammatory cytokines (IL-10, IL-1Ra). While ineffective in directly inducing innate memory per se, and unable to influence LPS-induced tolerance memory, AuNP significantly affected the memory response of BCG-primed cells, by inhibiting the secondary response in terms of both inflammatory and anti-inflammatory factor production. The reprogramming of BCG-induced memory towards a tolerance type of reactivity may open promising perspectives for the use of AuNP in immunomodulatory approaches to autoimmune and chronic inflammatory diseases., This research was funded by the EU Commission H2020 projects PANDORA (GA 671881) and ENDONANO (GA 812661), the Italian MIUR Flagship InterOmics project MEMORAT, and the Cluster project Medintech (CNT01_00177_962865).

Pollution of water with heavy metals is a global environmental problem whose impact is especially severe in developing countries. Among water-purification methods, adsorption of heavy metals has proven to be simple, versatile, and cost-effective. However, there is still a need to develop adsorbents with a capacity to remove multiple metal pollutants from the same water sample. Herein, we report the complementary adsorption capacities of metal-organic frameworks (here, UiO-66 and UiO-66-(SH)) and inorganic nanoparticles (iNPs; here, cerium-oxide NPs) into composite materials. These adsorbents, which are spherical microbeads generated in one step by continuous-flow spray-drying, efficiently and simultaneously remove multiple heavy metals from water, including As(III and V), Cd(II), Cr(III and VI), Cu(II), Pb(II), and Hg(II). We further show that these microbeads can be used as a packing material in a prototype of a continuous-flow water treatment system, in which they retain their metal-removal capacities upon regeneration with a gentle acidic treatment. As proof-of-concept, we evaluated these adsorbents for purification of laboratory water samples prepared to independently recapitulate each of two strongly polluted rivers: the Bone (Indonesia) and Buringanga (Bangladesh) rivers. In both cases, our microbeads reduced the levels of all the metal contaminants to below the corresponding permissible limits established by the World Health Organization (WHO). Moreover, we demonstrated the capacity of these microbeads to lower levels of Cr(VI) in a water sample collected from the Sarno River (Italy). Finally, to create adsorbents that could be magnetically recovered following their use in water purification, we extended our spray-drying technique to simultaneously incorporate two types of iNPs (CeO and FeO) into UiO-66-(SH), obtaining CeO/FeO@UiO-66-(SH) microbeads that adsorb heavy metals and are magnetically responsive.

The interaction of a living organism with external foreign agents is a central issue for its survival and adaptation to the environment. Nanosafety should be considered within this perspective, and it should be examined that how different organisms interact with engineered nanomaterials (NM) by either mounting a defensive response or by physiologically adapting to them. Herein, the interaction of NM with one of the major biological systems deputed to recognition of and response to foreign challenges, i.e., the immune system, is specifically addressed. The main focus is innate immunity, the only type of immunity in plants, invertebrates, and lower vertebrates, and that coexists with adaptive immunity in higher vertebrates. Because of their presence in the majority of eukaryotic living organisms, innate immune responses can be viewed in a comparative context. In the majority of cases, the interaction of NM with living organisms results in innate immune reactions that eliminate the possible danger with mechanisms that do not lead to damage. While in some cases such interaction may lead to pathological consequences, in some other cases beneficial effects can be identified., All authors were supported by the EU H2020 project PANDORA (GA 671881). The authors gratefully acknowledge the following additional financial support: EU H2020 project ENDONANO (GA 812661; PI, AD, VFP); the Italian Ministry of Research Flagship project InterOmics (DB, PI); the Austrian FWF Doctoral Program W1213: Immunity in Cancer and Allergy (ICA; AD, JHH); Catalan Agència de Gestió d'Ajuts Universitaris i de Recerca (2017‐SGR‐1431; VFP, NGB), Ramon y Cajal program (RYC‐2012‐10991; NGB); Severo Ochoa program from Spanish MINECO (Grant No. SEV‐2017‐0706; VFP, NGB); CERCA Programme/Generalitat de Catalunya (NGB). Supported by the project LO1509 of the Ministry of Education, Youth and Sports (Czech Republic) for providing the electron microscopy images.

Antioxidant nanoparticles have recently gained tremendous attention for their enormous potential in biomedicine. However, discrepant reports of either medical benefits or toxicity, and lack of reproducibility of many studies, generate uncertainties delaying their effective implementation. Herein, the case of cerium oxide is considered, a well‐known catalyst in the petrochemistry industry and one of the first antioxidant nanoparticles proposed for medicine. Like other nanoparticles, it is now described as a promising therapeutic alternative, now as threatening to health. Sources of these discrepancies and how this analysis helps to overcome contradictions found for other nanoparticles are summarized and discussed. For the context of this analysis, what has been reported in the liver is reviewed, where many diseases are related to oxidative stress. Since well‐dispersed nanoparticles passively accumulate in liver, it represents a major testing field for the study of new nanomedicines and their clinical translation. Even more, many contradictory works have reported in liver either cerium‐oxide‐associated toxicity or protection against oxidative stress and inflammation. Based on this, finally, the intention is to propose solutions to design improved nanoparticles that will work more precisely in medicine and safely in society., This research was funded by Ministerio de Economía y Competitividad, grants numbers PI15/00077 and PI19/00774 to G.C. and G.F.‐V.; Direccion General de Investigacion Cientifica y Técnica SAF 15‐64126 and RTI2018‐094734‐B‐C21 to W.J and SAF2016‐75358‐R to M.M‐R., cofinanced by FEDER, European Union, “A way of making Europe;” “Secretaria d'Universitats i Recerca del Departament d'Empresa i Coneixement de la Generalitat de Catalunya, convocatòria d'Indústria del Coneixement modalitat B,” grant number 2018_PROD_00187 to W.J., cofinanced by the European Union through the European Regional Development Fund (ERDF), “A way of making Europe;” CIBERehd is financed by the Instituto de Salud Carlos III; Wuyi University Funding for Hight Talents Introduction, grant number 2018TP010 to E.C. and 2018TP011 to M.Z.; Foundation from Department of Education of Guangdong Province, grant numbers 2016KCXTD005 and 2017KSYS010, to E.C. and M.Z.; National Natural Science Foundation of China (NFSC), grant number: 31950410536 to E.C.