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Noami Daems,1 Sébastien Penninckx,2 Inge Nelissen,3 Karen Van Hoecke,4 Thomas Cardinaels,4,5 Sarah Baatout,1 Carine Michiels,6 Stéphane Lucas,2 An Aerts11Radiobiology Research Unit, Interdisciplinary Biosciences, Institute for Environment, Health and Safety, Belgian Nuclear Research Centre (SCK.CEN), Mol, Belgium; 2Research Center for the Physics of Matter and Radiation-NARILIS, University of Namur, Namur, Belgium; 3Health Department, Flemish Institute For Technological Research (VITO), Mol, Belgium; 4Radiochemistry Expert Group, Institute for Nuclear Materials Science, Belgian Nuclear Research Centre (SCK.CEN), Mol, Belgium; 5Department of Chemistry, KU Leuven, Heverlee, Belgium; 6Unité de Recherche en Biologie Cellulaire-NARILIS, University of Namur, Namur, BelgiumPurpose: This study evaluates the cytotoxicity of AuNPs coated with polyallylamine (AuNPs-PAA) and conjugated or not to the epidermal growth factor receptor (EGFR)-targeting antibody Cetuximab (AuNPs-PAA-Ctxb) in normal human kidney (HK-2), liver (THLE-2) and microvascular endothelial (TIME) cells, and compares it with two cancer cell lines that are EGFR-overexpressing (A431) or EGFR-negative (MDA-MB-453).Results: Conjugation of Cetuximab to AuNPs-PAA increased the AuNPs-PAA-Ctxb interactions with cells, but reduced their cytotoxicity. TIME cells exhibited the strongest reduction in viability after exposure to AuNPs-PAA(±Ctxb), followed by THLE-2, MDA-MB-453, HK-2 and A431 cells. This cell type-dependent sensitivity was strongly correlated to the inhibition of thioredoxin reductase (TrxR) and glutathione reductase (GR), and to the depolarization of the mitochondrial membrane potential. Both are suggested to initiate apoptosis, which was indeed detected in a concentration- and time-dependent manner. The role of oxidative stress in AuNPs-PAA(±Ctxb)-induced cytotoxicity was demonstrated by co-incubation of the cells with N-acetyl L-cysteine (NAC), which significantly decreased apoptosis and mitochondrial membrane depolarization.Conclusion: This study helps to identify the cells and tissues that could be sensitive to AuNPs and deepens the understanding of the risks associated with the use of AuNPs in vivo.Keywords: cytotoxicity, EGFR, Cetuximab, oxidative stress

Bioconjugated gold nanoparticles (Au NPs) are a promising tool for pharmaceutical applications. However, the ecotoxicity of these types of NPs has hardly been studied. We investigated the ecotoxicity and uptake of 4-5 nm Au NPs to which two types of polymer coatings were attached. One coating was an amphiphilic polymer only and the other an amphiphilic coating to which 10 kDa polyethylene glycol chains were attached. In both 72 h algal growth inhibition tests with the alga Pseudokirchneriella subcapitata and in 24 h resazurin cytotoxicity tests with the rainbow trout gill cell line RTGill-W1, the pegylated Au NPs were found less toxic compared to the amphiphilic coated particles. No uptake or direct interaction between particles and algal cells was observed. However, uptake/adsorption in fish gill cells reached up to >106 particles/cell after 1 h and particles were eliminated for ≥96% after 24 h depuration. Both particle types were found within membrane enclosed vesicles in the cytoplasm of RTgill-W1 cells. [ABSTRACT FROM AUTHOR]

This paper describes a case study of an Outreach and Drop-in Centre (ODIC) established under the National Action Plan for Drug Demand Reduction, Ministry of Social Justice and Empowerment, Government of India. In the quantitative part, data were gathered from the ODIC office documents and analysed using MS Excel. Linear regression analysis demonstrated a relationship between the number of in-centre clients and the number of Community Outreach Programmes (COPs). Similarly, this study examined the relationship between the number of networks established and the number of participants in COPs. Hence, two regression lines were derived accordingly. In addition, qualitative data collected through key informant interviews corroborated the quantitative results. This case study highlights the importance of networks and COPs in increasing the reach of ODIC and ensuring the quality of services. Finally, in partnership with other government agencies, this ODIC sets a model for engaging marginalised adolescents in reducing substance abuse., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

A method was developed for the determination of the nuclide-specific concentrations of U, Pu, Nd and Gd in two types of spent nuclear fuel (UOx and Gd-enriched). High-performance ion chromatography (HPIC) was used to separate the target elements from one another while sector-field inductively coupled plasma-mass spectrometry (SF-ICP-MS) was used for their determination relying on isotope dilution for calibration. In order to obtain the best possible precision for these isotope ratios extracted from the transient HPIC-SF-ICP-MS signals, the SF-ICP-MS data acquisition parameters were optimized and the most suitable method for calculating the isotope ratios from the transient signals was identified. The point-by-point (PbP), linear regression slope (LRS) and peak area integration (PAI) approaches were compared in the latter context. It was found that data acquisition in the flat centre of the spectral flat top peak using a mass window of 25%, a dwell time of 10 ms and 20 samples per peak, while using PAI for isotope ratio calculation, gave the best precision on the isotope ratios extracted from the HPIC-SF-ICP-MS transient signals. These parameters were used in the determination of the nuclide-specific mass fractions of Pu, Nd and Gd in two types of spent nuclear fuel using isotope dilution HPIC-SF-ICP-MS. For U, which was present at a higher concentration, the element fraction was collected and analyzed off-line after dilution. For the other target elements, an online approach was used. An uncertainty budget estimation was made using the bottom-up approach for the resulting mass fractions, and the accuracy and precision obtained when using isotope dilution HPIC-SF-ICP-MS were compared with those obtained with the routinely used techniques, isotope dilution TIMS & alpha spectrometry (an ISO 17025 accredited method)., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Cetuximab-conjugated gold nanoparticles are known to target cancer cells, but display toxicity towards normal kidney, liver and endothelial cells in vitro . In this study, we investigated their pharmacokinetics, biodistribution and toxicity after intravenous administration in healthy mice. Our data showed that these nanoparticles were rapidly cleared from the blood and accumulated mainly in the liver and spleen with long-term retention. Acute liver injury, inflammatory activity and vascular damage were transient and negligible, as confirmed by the liver functionality tests and serum marker analysis. There was no sign of altered liver, kidney, lung and spleen morphology up to 4 weeks post-injection. After 6 months, kidney casts and splenic apoptosis appeared to be more prevalent than in the controls. Furthermore, occasional immune cell infiltration was observed in the lungs. Therefore, we recommend additional in vivo studies, in order to investigate the long-term toxicity and elimination of gold nanoparticles after multiple dosing in their preclinical validation as new targeted anti-cancer therapies.

High-pressure ion chromatography (HPIC) was coupled with sector field inductively coupled plasma-mass spectrometry (SF-ICP-MS) to separate plutonium (Pu), uranium (U), neodymium (Nd) and gadolinium (Gd) nuclides from isobaric nuclides and to quantify them with high sensitivity. In this study, mixed bed ion exchange columns CG5A and CS5A were used, from which Pu and U were eluted first using 1 M nitric acid. The lanthanides were then separated using a gradient of 0.1-0.15 M oxalic acid with the pH adjusted to 4.5. The HPIC-SF-ICP-MS method was validated using different sample matrices, i.e. spent nuclear fuel and soil. The method was found to be repeatable and gave rise to transient signals suitable for quantification of nuclide-specific concentrations using external calibration. In terms of accuracy, the HPIC-SF-ICP-MS measurement results were in good agreement with those obtained using thermal ionization mass spectrometry (TIMS). Finally, the method provides an improvement in sample throughput (≤60 minutes per sample) and reduces exposure of the operator to radiation compared to off-line gravitational chromatography followed by TIMS., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2019. Published by Elsevier B.V.)

Silica nanoparticles (NPs) belong to the industrially most important NP types. In a previous study it was shown that amorphous SiO(2) NPs of 12.5 and 27.0 nm are stable in algal growth inhibition assays and that their ecotoxic effects are related to NP surface area. Here, it was hypothesized and demonstrated that an alumina coating completely alters the particle-particle, particle-test medium and particle-algae interactions of SiO(2) NPs. Therefore, stability and surface characteristics, dissolution, nutrient adsorption and effects on algal growth rate of both alumina coated SiO(2) NPs and bare SiO(2) NPs in OECD algal test medium as a function of pH (6.0-8.6) and natural organic matter (NOM) contents (0-12 mg C/l) were investigated. Alumina coated SiO(2) NPs aggregated in all media and adsorbed phosphate depending on pH and NOM concentration. On the other hand, no aggregation or nutrient adsorption was observed for the bare SiO(2) NPs. Due to their positive surface charge, alumina coated SiO(2) NPs agglomerated with Pseudokirchneriella subcapitata. Consequently, algal cell density measurements based on cell counts were unreliable and hence fluorescent detection of extracted chlorophyll was the preferred method. Alumina coated SiO(2) NPs showed lower toxicity than bare SiO(2) NPs at concentrations ≥46 mg/l, except at pH 6.0. At low concentrations, no clear pH effect was observed for alumina coated SiO(2) NPs, while at higher concentrations phosphate deficiency could have contributed to the higher toxicity of those particles at pH 6.0-6.8 compared to higher pH values. Bare SiO(2) NPs were not toxic at pH 6.0 up to 220 mg/l. Addition of NOM decreased toxicity of both particles. For SiO(2) NPs the 48 h 20% effect concentration of 21.8 mg/l increased 2.6-21 fold and a linear relationship was observed between NOM concentration and effective concentrations. No effect was observed for alumina coated SiO(2) NPs in presence of NOM up to 1000 mg/l. All experiments point out that the alumina coating completely altered NP interactions. Due to the difference in surface composition the SiO(2) NPs, which had the smallest surface area, were more toxic to the alga than the alumina coated SiO(2) NPs. Hence, surface modification can dominate the effect of surface area on toxicity., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

The influence of pH (6.0-9.0), natural organic matter (NOM) (0-10 mg C/L) and ionic strength (IS) (1.7-40 mM) on 14 nm CeO₂ NP aggregation and ecotoxicity towards the alga Pseudokirchneriella subcapitata was assessed following a central composite design. Mean NP aggregate sizes ranged between 200 and 10000 nm. Increasing pH and IS enhanced aggregation, while increasing NOM decreased mean aggregate sizes. The 48 h-E(r)C20s ranged between 4.7 and 395.8 mg CeO₂/L. An equation for predicting the 48 h-E(r)C20 (48 h-E(r)C20 = -1626.4 × (pH) + 109.45 × (pH)² + 116.49 × ([NOM]) - 14.317 × (pH) × ([NOM]) + 6007.2) was developed. In a validation study with natural waters the predicted 48 h-E(r)C20 was a factor 1.08-2.57 lower compared to the experimental values., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

The ecological risk assessment of chemicals including nanoparticles is based on the determination of adverse effects on organisms and on the environmental concentrations to which biota are exposed. The aim of this work was to better understand the behavior of nanoparticles in the environment, with the ultimate goal of predicting future exposure concentrations in water. We measured the concentrations and particle size distributions of CeO(2) nanoparticles in algae growth medium and deionized water in the presence of various concentrations and two types of natural organic matter (NOM). The presence of natural organic matter stabilizes the CeO(2) nanoparticles in suspension. In presence of NOM, up to 88% of the initially added CeO(2) nanoparticles remained suspended in deionized water and 41% in algae growth medium after 12d of settling. The adsorbed organic matter decreases the zeta potential from about -15 mV to -55 mV. This reduces aggregation by increased electrostatic repulsion. The particle diameter, pH, electric conductivity and NOM content shows significant correlation with the fraction of CeO(2) nanoparticles remaining in suspension., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

Gene delivery has become an increasingly important strategy for treating a variety of human diseases, including infections, genetic disorders and tumours. To avoid the difficulties of using viral carriers, more and more non-viral gene delivery nanoparticles are developed. Among these new approaches polyethylene imine (PEI) is currently considered as one of the most effective polymer based method solution and considered as the gold standard. The toxicity of nanoparticles is a major concern when used for medical application. In this study we chose two nanoparticles for an in depth toxicological and ecotoxicological evaluation, one well characterized, PEI, and another novel polymer, poly(2-(dimethylamino)ethyl methacrylate) (PDMAEMA). In the present study we have assessed the toxicity of these cation nanoparticles as such and of the polyplexes - nanoparticles covered with DNA. As these nanoparticles are also frequently used in high volumes in various industries and as such may enter in the environment, we also made an initial assessment of ecotoxicological effects assessment. The following nanoparticles related aspects have been studied during the project: development and characterization, ecotoxicity, general toxicity and specific toxicity. To this end a battery of different tests was used. The conclusion of these tests is that toxicity is varying between different nanoparticles and between different DNA covering ratios. In general, in the different systems tested, the PEI polymer is more toxic than the PDMAEMA polymer. The same difference is seen for the polyplexes and the higher the charge ratio, the more toxic are the polyplexes. Our study also clearly shows the need for a broad spectrum of toxicity assays for a comprehensive risk assessment. Our study has performed such a comprehensive analysis of two biomedical nanoparticles.

Cerium dioxide nanoparticles (CeO2 NPs) are increasingly being used as a catalyst in the automotive industry. Consequently, increasing amounts of CeO2 NPs are expected to enter the environment where their fate in and potential impacts are unknown. In this paper we describe the fate and effects of CeO2 NPs of three different sizes (14, 20, and 29 nm) in aquatic toxicity tests. In each standard test medium (pH 7.4) the CeO2 nanoparticles aggregated (mean aggregate size approximately 400 nm). Four test organisms covering three different trophic levels were investigated, i.e., the unicellular green alga Pseudokirchneriella subcapitata, two crustaceans: Daphnia magna and Thamnocephalus platyurus, and embryos of Danio rerio. No acute toxicity was observed for the two crustaceans and D. rerio embryos, up to test concentrations of 1000, 5000, and 200 mg/L, respectively. In contrast, significant chronic toxicity to P. subcapitata with 10% effect concentrations (EC10s) between 2.6 and 5.4 mg/L was observed. Food shortage resulted in chronic toxicity to D. magna, for wich EC10s of > or = 8.8 and < or = 20.0 mg/L were established. Chronic toxicity was found to increase with decreasing nominal particle diameter and the difference in toxicity could be explained by the difference in surface area. Using the data set, PNEC(aquatic)S > or = 0.052 and < or = 0.108 mg/L were derived. Further experiments were performed to explain the observed toxicity to the most sensitive organism, i.e., P. subcapitata. Toxicity could not be related to a direct effect of dissolved Ce or CeO2 NP uptake or adsorption, nor to an indirect effect of nutrient depletion (by sorption to NPs) or physical light restriction (through shading by the NPs). However, observed clustering of NPs around algal cells may locally cause a direct or indirect effect.

To date, (eco)toxicological information on industrial nanoparticles is very limited. In the present study, the hypothesis that the ecotoxicity of nanoparticles (NPs) is related to their surface area and not to their mass was tested using a freshwater green algal species. Particle diameter and morphology were assessed using light scattering and electron microscopy techniques. To assess the toxicity of silica (SiO2) nanoparticles, the growth inhibition of the alga Pseudokirchneriella subcapitata when exposed to stable silica suspensions was monitored. Commercial LUDOX suspensions of nanoparticles with 12.5 and 27.0 nm diameter were found to be toxic, with 72-h 20% effect concentrations for growth rate (E(r)C20) values +/- standard deviation (n = 5) of 20.0 +/- 5.0 and 28.8 +/- 3.2 mg/L, respectively. The toxicity was attributable to the solid nanospheres, because no aggregation was observed and dissolution of the nanoparticles was negligible. When expressing the concentration as a surface area, the difference in toxicity was not significant. In the latter case, 72-h E(r)C20 values +/- standard deviation (n = 5) were 4.7 +/- 1.2 and 3.9 +/- 0.4 m2/L. Silica bulk material was found to be nontoxic up to 1 g/L. In an additional experiment with 100 mg/L of 12.5 and 27.0 nm SiO2 NPs, the interaction between the nanoparticles and algal cells was studied using transmission electron microscopy. Although the particles clearly adhered to the outer cell surface, no evidence was found for particle uptake.