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During the twenty-first century, engineered nanomaterials (ENMs) have attracted rising interest, globally revolutionizing all industrial sectors. The expanding world population and the implementation of new global policies are increasingly pushing society toward a bioeconomy, focused on fostering the adoption of bio-based nanomaterials that are functional, cost-effective, and potentially secure to be implied in different areas, the medical field included. This research was focused on silica nanoparticles (SiO2-NPs) of bio-based and synthetic origin. SiO2-NPs are composed of silicon dioxide, the most abundant compound on Earth. Due to their characteristics and biocompatibility, they are widely used in many applications, including the food industry, synthetic processes, medical diagnosis, and drug delivery. Using zebrafish embryos as in vivo models, we evaluated the effects of amorphous silica bio-based NPs from rice husk (SiO2-RHSK NPs) compared to commercial hydrophilic fumed silica NPs (SiO2-Aerosil200). We evaluated the outcomes of embryo exposure to both nanoparticles (NPs) at the histochemical and molecular levels to assess their safety profile, including developmental toxicity, neurotoxicity, and pro-inflammatory potential. The results showed differences between the two silica NPs, highlighting that bio-based SiO2-RHSK NPs do not significantly affect neutrophils, macrophages, or other innate immune system cells. [ABSTRACT FROM AUTHOR]

The results presented summarise the ones obtained in the coordinated research project Tosca, which extensively analysed the impact of Milan urban PM on human health. The molecular markers of exposure and effects of seasonally and size-fractionated PMs (summer and winter PM10, PM2.5) were investigated in in vitro (human lung cell lines) and in vivo (mice) systems. The results obtained by the analyses of cytotoxic, pro-inflammatory and genotoxic parameters demonstrate that the biological responses are strongly dependent upon the PM samples seasonal and dimensional variability, that ultimately reflect their chemical composition and source. In fact summer PM10, enriched in crustal elements and endotoxins, was the most cytotoxic and pro-inflammatory fraction, while fine winter PMs induced genotoxic effects and xenobiotic metabolizing enzymes (like CYP1B1) production, likely as a consequence of the higher content in combustion derived particles reach in PAHs and heavy toxic metals. These outcomes outline the need of a detailed knowledge of the PMs physico-chemical composition on a local scale, coupled with the biological hazard directly associated to PM exposure. Apparently this is the only way allowing scientists and police-makers to establish the proper relationships between the respirable PM quantity/quality and the health outcomes described by clinicians and epidemiologists.

The widespread use of silver nanoparticles (Ag NPs) in food and consumer products suggests the relevance of human oral exposure to these nanomaterials (NMs) and raises the possibility of adverse effects in the gastrointestinal tract. The aim of this study was to investigate the toxicity of Ag NPs in a human intestinal cell line, either uncoated or coated with polyvinylpyrrolidone (Ag PVP) or hydroxyethylcellulose (Ag HEC) and digested in simulated gastrointestinal fluids. Physicochemical transformations of Ag NPs during the different stages of in vitro digestion were identified prior to toxicity assessment. The strategy for evaluating toxicity was constructed on the basis of adverse outcome pathways (AOPs) showing Ag NPs as stressors. It consisted of assessing Ag NP cytotoxicity, oxidative stress, genotoxicity, perturbation of the cell cycle and apoptosis. Ag NPs caused a concentration-dependent loss of cell viability and increased the intracellular level of reactive oxygen species as well as DNA damage and perturbation of the cell cycle. In vitro digestion of Ag NPs did not significantly modulate their toxicological impact, except for their genotoxicity. Taken together, these results indicate the potential toxicity of ingested Ag NPs, which varied depending on their coating but did not differ from that of non-digested NPs. [ABSTRACT FROM AUTHOR]

Furthermore, the continuous development during the last two decades of engineered nanoparticles (NPs), that may be defined as particles with a least one dimension lower than 100 nm, constitute an additional burden to air pollution by these sub-micrometric particles. In the recent years, the ultrafine particles (UFPs), which represents the particles with aerodynamic diameter lower than 100 nm, become of primary interest for understanding the impacts of airborne pollution on health. The understanding of potential health risks of UFPs and NPs and specifically associated pollutants is a complex field of research that requires integrative and multidisciplinary approaches. [Extracted from the article]

Silver nanoparticles (Ag NPs) are among the most widely used metal-based nanomaterials (NMs) and their applications in different products, also as antibacterial additives, are increasing. In the present manuscript, according to an adverse outcome pathway (AOP) approach, we tested two safe-by-design (SbD) newly developed Ag NPs coated with hydroxyethyl cellulose (HEC), namely AgHEC powder and AgHEC solution. These novel Ag NPs were compared to two reference Ag NPs (naked and coated with polyvinylpyrrolidone—PVP). Cell viability, inflammatory response, reactive oxygen species, oxidative DNA damage, cell cycle, and cell–particle interactions were analyzed in the alveolar in vitro model, A549 cells. The results show a different toxicity pattern of the novel Ag NPs compared to reference NPs and that between the two novel NPs, the AgHEC solution is the one with the lower toxicity and to be further developed within the SbD framework. [ABSTRACT FROM AUTHOR]

Microplastics (MPs) represent a worldwide emerging relevant concern toward human and environmental health due to their intentional or unintentional release. Human exposure to MPs by inhalation is predicted to be among the most hazardous. MPs include both engineered, or primary MPs, and secondary MPs, materials obtained by fragmentation from any plastic good. The major part of the environmental MPs is constituted by the second ones that are irregular in size, shape and composition. These features make the study of the biological impact of heterogenous MPs of extremely high relevance to better estimate the real toxicological hazards of these materials on human and environmental organisms. The smallest fractions of plastic granules, relying on the micron‐sized scale, can be considered as the most abundant component of the environmental MPs, and for this reason, they are typically used to perform toxicity tests using in vitro systems representative of an inhalation exposure scenario. In the present work, MPs obtained from industrial treatment of waste plastics (wMPs < 50 μm) were investigated, and after the physico‐chemical characterization, the cytotoxic, inflammatory and genotoxic responses, as well as the modality of wMPs interactions with alveolar lung cells, were determined. Obtained results indicated that, at high concentrations (100 μg/ml) and prolonged exposure time (48 h), wMPs affect biological responses by inducing inflammation and genotoxicity, as a result of the cell–wMP interactions, also including the uptake of the smaller particles. The toxicity of waste microplastics (wMPs < 50 μm), recovered from industrially recycled plastic granules, was evaluated by using an in vitro model of the lung (A549 cell line), in order to understand the biological outcomes induced by the inhalation of microplastics. Data showed that a prolonged (48 h) exposure to wMPs (100 μg/ml) induced cell viability reduction, inflammation and genotoxicity, as results of lung cell and wMPs interactions. [ABSTRACT FROM AUTHOR]

Zinc oxide (ZnO) is the most efficient curing activator employed in the industrial rubber production. However, ZnO and Zn(II) ions are largely recognized as an environmental hazard being toxic to aquatic organisms, especially considering Zn(II) release during tire lifecycle. In this context, aiming at reducing the amount of microcrystalline ZnO, a novel activator was recently synthetized, constituted by ZnO nanoparticles (NPs) anchored to silica NPs (ZnO-NP@SiO2-NP). The objective of this work is to define the possible hazards deriving from the use of ZnO-NP@SiO2-NP compared to ZnO and SiO2 NPs traditionally used in the tire industry. The safety of the novel activators was assessed by in vitro testing, using human lung epithelial (A549) and immune (THP-1) cells, and by the in vivo model zebrafish (Danio rerio). The novel manufactured nanomaterial was characterized morphologically and structurally, and its effects evaluated in vitro by the measurement of the cell viability and the release of inflammatory mediators, while in vivo by the Fish Embryo Acute Toxicity (FET) test. Resulting data demonstrated that ZnO-NP@SiO2-NP, despite presenting some subtoxic events, exhibits the lack of acute effects both in vitro and in vivo, supporting the safe-by-design development of this novel material for the rubber industry. [ABSTRACT FROM AUTHOR]

Road construction takes a heavy toll on the environment. Therefore, innovative strategies to improve the environmental performances of this sector are needed, and the use of recycled materials (e.g., plastic) has been recently pursued to achieve this goal. The present work aims to (i) assess the environmental benefits deriving from the use of recycled hard plastics in combination with graphene to generate a new bitumen modifier and related asphalt mixture (AM) formulations (ii) to compare the performance of the bitumen modified using this new modifier with the bitumen modified using a traditional polymer (Styrene-Butadiene-Styrene, SBS) and the non-modified bitumen. A detailed Life Cycle Assessment (LCA) study was performed according to a cradle-to-cradle approach. Different scenarios were compared, including the variability of the pavement's layers thickness and the amount of reclaimed asphalt pavement during the road maintenance cycles. The results demonstrated that the addition of the innovative modifier enhanced the structural performance of AMs, which turns into pavement extended durability, reduced maintenance cycles as well as into reduction in raw material use. The innovative asphalt modifier also creates a synergistic effect by offering a valuable alternative to hard plastic incineration by using it as a secondary raw material. This analysis allowed us to indicate the new-modified AM as the solution with the least environmental burden in all impact categories, suggesting its significant role in implementing new strategies to improve the environmental sustainability of road pavements. [ABSTRACT FROM AUTHOR]

Multidrug antimicrobial resistance is a constantly growing health care issue associated with increased mortality and morbidity, and huge financial burden. Bacteria frequently form biofilm communities responsible for numerous persistent infections resistant to conventional antibiotics. Herein, novel nanoparticles (NPs) loaded with the natural bactericide farnesol (FSL NPs) are generated using high-intensity ultrasound. The nanoformulation of farnesol improved its antibacterial properties and demonstrated complete eradication of Staphylococcus aureus within less than 3 h, without inducing resistance development, and was able to 100% inhibit the establishment of a drug-resistant S. aureus biofilm. These antibiotic-free nano-antimicrobials also reduced the mature biofilm at a very low concentration of the active agent. In addition to the outstanding antibacterial properties, the engineered nano-entities demonstrated strong antiviral properties and inhibited the spike proteins of SARS-CoV-2 by up to 83%. The novel FSL NPs did not cause skin tissue irritation and did not induce the secretion of anti-inflammatory cytokines in a 3D skin tissue model. These results support the potential of these bio-based nano-actives to replace the existing antibiotics and they may be used for the development of topical pharmaceutic products for controlling microbial skin infections, without inducing resistance development. [ABSTRACT FROM AUTHOR]

Abstract Background It is estimated that over 80% of respirable particulate matter (PM10) in cities comes from road transport and that tire and brake wear are responsible for the 3–7% emission of it. Data on the indicators of environmental impact of tire debris (TD), originated from the tire abrasion on roads, are extremely scarce, even though TD contains chemicals (zinc and organic compounds) which can be released in the environment. Methods TD particle morphology was analysed with SEM, TEM and FIB instruments. TD eluates and TD organic extracts were tested at dilution series on human cell lines and Xenopus laevis embryos. 50 and 100 g/L TD were used for the eluates obtained after 24 h at pH 3 and the quantity of zinc present was measured with a ICP-AES. Eluates diluted to 1%, 10%, 50% in culture media and undiluted were used on X. laevis embryos in the FETAX test. HepG2 cells were exposed for 24 h to 0.05 – 50 μg/ml of zinc salt while A549 cells were exposed for 24, 48 and 72 h to 10, 50, 60, or 75 μg/ml of TD extract. X. laevis embryos were exposed to 50, 80, 100, or 120 μg/ml TD extract. Results The solution of undiluted 50 g/L TD produced 80.2% mortality (p < 0.01) in X. laevis embryos and this toxic effect was three times greater than that produced by 100 g/L TD. Zn accumulation in HepG2 cells was evident after 4 h exposure. A549 cells exposed to TD organic extract for 72 h presented a modified morphology, a decrease in cell proliferation and an increase in DNA damage as shown by comet assay. The dose 80 μg/ml of TD extract produced 14.6% mortality in X. laevis embryos and 15.9% mortality at 120 μg/ml. Treatment with 80, 100, or 120 μg/ml TD organic extract increased from 14.8% to 37.8% malformed larvae percentages compared to 5.6% in the control. Conclusion Since the amount of Zn leached from TD is related to pH, aggregation of particles and elution process, the quantity of TD present in the environment has to be taken into account. Moreover the atmospheric conditions, which may deeply influence the particle properties, have to be considered. The TD organic fraction was toxic for cells and organisms. Thus, because of its chemical components, TD may have a potential environmental impact and has to be further investigated.

The use of CuO nanoparticles (NPs) has increased greatly and their potential effects on human health need to be investigated. Differentiated Caco‐2 cells were treated from the apical (Ap) and the basolateral (Bl) compartment with different concentrations (0, 10, 50 and 100 μg/mL) of commercial or sonochemically synthesized (sono) CuO NPs. Sono NPs were prepared in ethanol (CuOe) or in water (CuOw), obtaining CuO NPs differing in size and shape. The effects on the Caco‐2 cell barrier were assessed via transepithelial electrical resistance (TEER) evaluation just before and after 1, 2 and 24 hours of exposure and through the analysis of cytokine release and biomarkers of oxidative damage to proteins after 24 hours. Sono CuOe and CuOw NPs induced a TEER decrease with a dose‐dependent pattern after Bl exposure. Conversely, TEER values were not affected by the Ap exposure to commercial CuO NPs and, concerning the Bl exposure, only the lowest concentration tested (10 μg/mL) caused a TEER decrease after 24 hours of exposure. An increased release of interleukin‐8 was induced by sono CuO NPs after the Ap exposure to 100 μg/mL and by sono and commercial CuO after the Bl exposure to all the concentrations. No effects of commercial and sono CuO NPs on interleukin‐6 (with the only exception of 100 μg/mL Bl commercial CuO) and tumor necrosis factor‐α release were observed. Ap treatment with commercial and CuOw NPs was able to induce significant alterations on specific biomarkers of protein oxidative damage (protein sulfhydryl group oxidation and protein carbonylation). Differentiated Caco‐2 cells were exposed from the apical and basolateral compartment to 0, 10, 50 and 100 μg/mL of sonochemical (synthesized in ethanol or in water) and commercial CuO nanoparticles (NPs), then trans‐epithelial electrical resistance (TEER), cytokine release and biomarkers of protein oxidation were investigated. TEER was affected mostly by the Bl exposure to sonochemical Cu NPs. CuO NPs also induced a significant (P <.05) release of interleukins 8 and 6, and alterations in biomarkers of protein oxidation. [ABSTRACT FROM AUTHOR]

Iron nanoparticles (NPs) have been proposed as a tool in very different fields such as environmental remediation and biomedical applications, including food fortification against iron deficiency, even if there is still concern about their safety. Here, we propose Xenopus laevis embryos as a suitable model to investigate the toxicity and the bio-interactions at the intestinal barrier of Fe3O4 and zerovalent iron (ZVI) NPs compared to Fe(II) and (III) salts in the 5 to 100 mg Fe/L concentration range using the Frog Embryo Teratogenesis Assay in Xenopus (FETAX). Our results demonstrated that, at concentrations at which iron salts induce adverse effects, both iron NPs do not cause acute toxicity or teratogenicity even if they accumulate massively in the embryo gut. Prussian blue staining, confocal and electron microscopy allowed mapping of iron NPs in enterocytes, along the paracellular spaces and at the level of the basement membrane of a well-preserved intestinal epithelium. Furthermore, the high bioaccumulation factor and the increase in embryo length after exposure to iron NPs suggest greater iron intake, an essential element for organisms. Together, these results improve the knowledge on the safety of orally ingested iron NPs and their interaction with the intestinal barrier, useful for defining the potential risks associated with their use in food/feed fortification. [ABSTRACT FROM AUTHOR]

Airborne particulate (PM) components from fossil fuel combustion can induce oxidative stress initiated by reactive oxygen species (ROS) that are strongly correlated with airway inflammation and asthma. A valid biomarker of airway inflammation is fractionated exhaled nitric oxide (FENO). The oxidative potential of PM2.5 can be evaluated with the dithiothreitol (DTT) dosage, which represents both ROS chemically produced and intracellular ROS of macrophages. This correlates with quality indicators of the internal environment and ventilation strategies such as dilution and removal of airborne contaminants. [ABSTRACT FROM AUTHOR]

Aim: To demonstrate that cobalt nanoparticles doses are safe for use in humans and to understand the consequences of the particulate effects, which may persist inside the cells. Materials & methods: Human adipose stem cells were used. We evaluated cell recovery by viability test, morphology and ultrastructure using electronic and optical microscopy, while gene expression was assessed utilizing real-time PCR. Results: After exposure, most stem cells recovered their normal function. Co3O4-nanoparticles remained inside the cell for the entirety of the considered time. A slight modification of gene expression was observed in the exposed cells. Conclusion: After exposure to 100 M cobalt nanoparticles, most cells returned to normal function. Nanoparticle toxicity was due to ions released by dissolution as well as from the nanoparticles themselves. [ABSTRACT FROM AUTHOR]

In the current study, we evaluated the modulatory effects of size and surface coating/charge of AgNPs on their toxicity to a unicellular yeast Saccharomyces cerevisiae BY4741 – a fungal model. For that, the toxicity of a set of 10 and 80 nm citrate-coated (negatively charged) and branched polyethylenimine (bPEI) coated (positively charged) AgNPs was evaluated in parallel with AgNO3 as ionic control. Yeast cells were exposed to different concentrations of studied compounds in deionized water for 24 h at 30 °C and evaluated for the viability by the post-exposure colony-forming ability. Particle-cell interactions were assessed by SEM, TEM and confocal laser scanning microscopy (CLSM) in the reflection mode. AgNPs toxicity to yeast was size and charge-dependent: 24-h IC50 values ranged from 0.04 (10nAg-bPEI) up to 8.3 mg Ag/L (80nAg-Cit). 10 nm AgNPs were 5–27 times more toxic than 80 nm AgNPs and bPEI-AgNPs 8–44 times more toxic than citrate-AgNPs. SEM and TEM visualization showed that bPEI-AgNPs but not citrate-AgNPs adsorbed onto the yeast cell's surface. However, according to CLSM all the studied AgNPs, whatever the size and coating, ended up within the yeast cell. Toxicity of citrate-AgNPs was largely explained by the dissolved Ag ions but the bPEI-AgNPs showed mainly particle-driven effects leading to the cellular internalization and/or to more pronounced dissolution of AgNPs in the close vicinity of the cell wall. Therefore, the size, and especially the coating/charge of AgNPs can be efficiently used for the design of new more efficient antifungals. [ABSTRACT FROM AUTHOR]