Coating Dependent In Vitro Biocompatibility of New Fe-Si Nanoparticles

Magnetic nanoparticles offer multiple utilization possibilities in biomedicine. In this context, the interaction with cellular structures and their biological effects need to be understood and controlled for clinical safety. New magnetic nanoparticles containing metallic/carbidic iron and elemental silicon phases were synthesized by laser pyrolysis using Fe(CO)5 vapors and SiH4 gas as Fe and Si precursors, then passivated and coated with biocompatible agents, such as l-3,4-dihydroxyphenylalanine (l-DOPA) and sodium carboxymethyl cellulose (CMC-Na). The resulting magnetic nanoparticles were characterized by XRD, EDS, and TEM techniques. To evaluate their biocompatibility, doses ranging from 0–200 µg/mL hybrid Fe-Si nanoparticles were exposed to Caco2 cells for 24 and 72 h. Doses below 50 μg/mL of both l-DOPA and CMC-Na-coated Fe-Si nanoparticles induced no significant changes of cellular viability or membrane integrity. The cellular internalization of nanoparticles was dependent on their dispersion in culture medium and caused some changes of F-actin filaments organization after 72 h. However, reactive oxygen species were generated after exposure to 25 and 50 μg/mL of both Fe-Si nanoparticles types, inducing the increase of intracellular glutathione level and activation of transcription factor Nrf2. At nanoparticles doses below 50 μg/mL, Caco2 cells were able to counteract the oxidative stress by activating the cellular protection mechanisms. We concluded that in vitro biological responses to coated hybrid Fe-Si nanoparticles depended on particle synthesis conditions, surface coating, doses and incubation time

Synthesis, Characterization, and Toxicity Evaluation of Dextran-Coated Iron Oxide Nanoparticles

We report the synthesis of dextran-coated iron oxide magnetic nanoparticles (DIO-NPs) with spherical shape and uniform size distribution as well as their accumulation and toxic effects on Jurkat cells up to 72 h. The characterization of dextran-coated maghemite nanoparticles was done by X-ray diffraction and dynamic light scattering analyses, transmission electron microscopy imaging, attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectroscopy, magnetic hysteresis, and relaxometry measurements. The quantification of DIO-NPs intracellular uptake showed a progressive accumulation of iron as a function of time and dose accompanied by additional lysosome formation and an increasing darkening exhibited by a magnetic resonance imaging (MRI) scanner. The cytotoxicity assays revealed a decrease of cell viability and a loss of membrane integrity in a time- and dose-dependent manner. Exposure to DIO-NPs determined an increase in reactive oxygen species level up to 72 h. In the first two days of exposure, the level of reduced glutathione decreased and the amount of malondyaldehyde increased, but at the end of the experiment, their concentrations returned to control values. These nanoparticles could be used as contrast agents for MRI but several parameters concerning their interaction with the cells should be taken into consideration for a safe utilization

The Influence of Fly Ash on the Mechanical Properties of Water Immersed All Waste Composites

The paper presents new value-added composite materials prepared by recycling tire rubber, polyethene terephthalate (PET), high-density polyethene (HDPE), wood sawdust, and fly ash. The composites were manufactured through the compression molding technique for three temperatures (150 °C, 160 °C, and 190 °C) previously optimized. The addition of fly ash as reinforcement in polymer blends is a viable route to improve the composite” properties. The paper aims to assess the effect of fly ash on the mechanical properties and water stability of the new all waste composites considering their applications as outdoor products. The static tensile (stress-strain behavior) and compression properties of the composites were tested. The fly ash composites were characterized in terms of wetting behavior and surface energies (contact angle measurements); chemical structure of the new interface developed between composite” components (FTIR analysis), crystalline structure (XRD analysis), surface morphology and topography (SEM, AFM). The addition of fly ash promoted the development of the hybrid interfaces in the new composites, as FTIR analysis has shown, which, in turn, greatly improved the mechanical and water resistance. The novel all waste composites exhibited lower surface energies, larger contact angles, and smoother morphologies when compared to those with no fly ash. Overall, the study results have revealed that fly ash has improved the mechanical strength and water stability of the composites through the formation of strong hybrid interfaces. The study results show optimal water stability and tensile strength for 0.5% fly ash composites cured at 190 °C and optimal compressive strength with good water stability for 1% fly ash composite cured at 150 °C

CYTOGENETIC EFFECTS INDUCED BY PHENOLIC COMPOUNDS IN LYCOPERSICON ESCULENTUM MILL

The aim of this paper is to evaluate the effects of the phenolic compounds extracted from spruce bark on cells from the radicular apex of Lycopersicon esculentum Mill. We found that different concentrations of polyphenols and the time of treatment modified the frequency of cells division and the number of mitotic ana-telophases with aberrations

New Insights into the Biological Response Triggered by Dextran-Coated Maghemite Nanoparticles in Pancreatic Cancer Cells and Their Potential for Theranostic Applications

Iron oxide nanoparticles are one of the most promising tools for theranostic applications of pancreatic cancer due to their unique physicochemical and magnetic properties making them suitable for both diagnosis and therapy. Thus, our study aimed to characterize the properties of dextran-coated iron oxide nanoparticles (DIO-NPs) of maghemite (γ-Fe2O3) type synthesized by co-precipitation and to investigate their effects (low-dose versus high-dose) on pancreatic cancer cells focusing on NP cellular uptake, MR contrast, and toxicological profile. This paper also addressed the modulation of heat shock proteins (HSPs) and p53 protein expression as well as the potential of DIO-NPs for theranostic purposes. DIO-NPs were characterized by X-ray diffraction (XRD), transmission electron microscopy (TEM), dynamic light scattering analyses (DLS), and zeta potential. Pancreatic cancer cells (PANC-1 cell line) were exposed to different doses of dextran-coated ɣ-Fe2O3 NPs (14, 28, 42, 56 μg/mL) for up to 72 h. The results revealed that DIO-NPs with a hydrodynamic diameter of 16.3 nm produce a significant negative contrast using a 7 T MRI scanner correlated with dose-dependent cellular iron uptake and toxicity levels. We showed that DIO-NPs are biocompatible up to a concentration of 28 μg/mL (low-dose), while exposure to a concentration of 56 μg/mL (high-dose) caused a reduction in PANC-1 cell viability to 50% after 72 h by inducing reactive oxygen species (ROS) production, reduced glutathione (GSH) depletion, lipid peroxidation, enhancement of caspase-1 activity, and LDH release. An alteration in Hsp70 and Hsp90 protein expression was also observed. At low doses, these findings provide evidence that DIO-NPs could act as safe platforms in drug delivery, as well as antitumoral and imaging agents for theranostic uses in pancreatic cancer

Exposure to Iron Oxide Nanoparticles Coated with Phospholipid-Based Polymeric Micelles Induces Renal Transitory Biochemical and Histopathological Changes in Mice

The renal toxicity induced by the intravenously injected iron oxide nanoparticles (IONPs) encapsulated in phospholipid-based polymeric micelles was studied in CD1 mice for 2 weeks. Two doses of 5 and 15 mg of Fe/kg bodyweight of NPs or saline solution (control) were tested, and the levels of antioxidant enzyme activities, oxidative stress parameters, and the expressions of kidney fibrosis biomarkers were analyzed. The enzymatic activities of superoxide dismutase, catalase, glutathione peroxidase, glutathione-S-transferase, glutathione reductase, and glucose-6-phosphate dehydrogenase in the kidney were significantly decreased compared to the control in the first 3 days followed by a recovery up to 14 days. Concomitantly, a significant increase in lipid peroxidation (malondialdehyde) levels and a decrease in protein thiol groups were recorded. Moreover, increases in the expressions of T cell immunoglobulin and mucin domain 1 (TIM-1) and transforming growth factor-β (TGF-β) were observed in mouse tissue samples in the first week, which were more pronounced for the higher dose. The results suggested the role of oxidative stress as a mechanism for induced toxicity in mice kidneys after the IV administration of IONPs encapsulated in phospholipid-based polymeric micelles but also the capacity of the kidneys’ defense systems to revert efficiently the biochemical modifications that were moderate and for short duration

Response of the Endogenous Antioxidant Defense System Induced in RAW 264.7 Macrophages upon Exposure to Dextran-Coated Iron Oxide Nanoparticles

Presently, iron oxide nanoparticles are the only ones approved for clinical use as contrast agents in magnetic resonance imaging (MRI). Even though there is a high demand for these types of nanoparticles both for clinical use as well as for research, there are difficulties in obtaining stable nanoparticles with reproducible properties. In this context, in this study, we report the obtaining by an adapted coprecipitation method of dextran-coated maghemite nanoparticles (ɤ-Fe2O3 NPs). The morphology and structure of the dextran-coated maghemite nanoparticles (ɤ-Fe2O3 NPs) were determined using scanning electron microscopy (SEM) and transmission electron microscopy (TEM). The TEM and SEM micrographs highlighted the obtaining of particles of nanometric size and spherical shape morphology. Furthermore, the high-resolution transmission electron microscopy (HRTEM), as well as selected area diffraction (SAED), revealed that the obtained samples presented the structure of cubic maghemite. In this study, we also explored the effects of the co-precipitation synthesized dextran-coated maghemite nanoparticles (ɤ-Fe2O3 NPs) on the redox status of macrophages. For cytotoxicity evaluation of these NPs, murine macrophages (RAW 264.7 cell line) were exposed to different concentrations of dextran-coated maghemite nanoparticles (ɤ-Fe2O3 NPs) corresponding to 0–500 μg Fe3+/mL and incubated for 24, 48, and 72 h. Intracellular iron uptake, changes in the oxidative stress parameters (reactive oxygen species production and malondialdehyde level), and the activity of antioxidant enzymes, as well as GSH concentration in cells, were evaluated after incubation with a lower (50 μg Fe3+/mL) and higher (500 μg Fe3+/mL) dose of NPs. The results indicated a significant decrease in RAW 264.7 cell viability after 72 h in the presence of NPs at concentrations above 25 μg Fe3+/mL. An important accumulation of NPs, dependent on dose and exposure time, was detected in macrophages, but it induced only a limited raise in the oxidative status. We showed here that the antioxidant capacity of RAW 264.7 macrophages was efficient in counteracting dextran-coated maghemite nanoparticles (ɤ-Fe2O3 NPs) toxicity even at higher doses

Response of the Endogenous Antioxidant Defense System Induced in RAW 264.7 Macrophages upon Exposure to Dextran-Coated Iron Oxide Nanoparticles

Presently, iron oxide nanoparticles are the only ones approved for clinical use as contrast agents in magnetic resonance imaging (MRI). Even though there is a high demand for these types of nanoparticles both for clinical use as well as for research, there are difficulties in obtaining stable nanoparticles with reproducible properties. In this context, in this study, we report the obtaining by an adapted coprecipitation method of dextran-coated maghemite nanoparticles (ɤ-Fe2O3 NPs). The morphology and structure of the dextran-coated maghemite nanoparticles (ɤ-Fe2O3 NPs) were determined using scanning electron microscopy (SEM) and transmission electron microscopy (TEM). The TEM and SEM micrographs highlighted the obtaining of particles of nanometric size and spherical shape morphology. Furthermore, the high-resolution transmission electron microscopy (HRTEM), as well as selected area diffraction (SAED), revealed that the obtained samples presented the structure of cubic maghemite. In this study, we also explored the effects of the co-precipitation synthesized dextran-coated maghemite nanoparticles (ɤ-Fe2O3 NPs) on the redox status of macrophages. For cytotoxicity evaluation of these NPs, murine macrophages (RAW 264.7 cell line) were exposed to different concentrations of dextran-coated maghemite nanoparticles (ɤ-Fe2O3 NPs) corresponding to 0–500 μg Fe3+/mL and incubated for 24, 48, and 72 h. Intracellular iron uptake, changes in the oxidative stress parameters (reactive oxygen species production and malondialdehyde level), and the activity of antioxidant enzymes, as well as GSH concentration in cells, were evaluated after incubation with a lower (50 μg Fe3+/mL) and higher (500 μg Fe3+/mL) dose of NPs. The results indicated a significant decrease in RAW 264.7 cell viability after 72 h in the presence of NPs at concentrations above 25 μg Fe3+/mL. An important accumulation of NPs, dependent on dose and exposure time, was detected in macrophages, but it induced only a limited raise in the oxidative status. We showed here that the antioxidant capacity of RAW 264.7 macrophages was efficient in counteracting dextran-coated maghemite nanoparticles (ɤ-Fe2O3 NPs) toxicity even at higher doses

Recursive feature elimination in random forest classification supports nanomaterial grouping

Nanomaterials (NMs) can be produced in numerous different variants of the same chemical substance. An in-depth safety assessment for each variant by generating test data will simply not be feasible. Thus, NM grouping approaches that would significantly reduce the time and amount of testing for novel NMs are urgently needed. However, identifying structurally similar NM variants remains challenging as many physico-chemical properties could be relevant. Here, we aimed at emphasizing on the value of machine learning models in the process of NM grouping by considering a case study on eleven selected, well-characterized NMs. To that end, we linked physico-chemical properties of these NMs to characterized hallmarks for inhalation toxicity. We applied unsupervised and supervised machine learning techniques to determine which combination of properties is most predictive. First, we assessed NM similarity in an unsupervised manner using principal component analysis (PCA) followed by subsequent superposition of activity labels combined with a k-nearest neighbors approach. Then, we used random forests (RFs) as a supervised machine learning technique which directly uses the knowledge on the activity class in the process of defining NM similarity. Thus, similarity was defined only on those properties showing the highest correlation with the activity and therefore had the highest discriminative power. In order to improve the performance, we then used recursive feature elimination (RFE) to delete uninformative features biasing the results. The best performance was achieved by the reduced RF model based on RFE where a balanced accuracy of 0.82 was obtained. Out of eleven different properties we determined zeta potential, redox potential and dissolution rate to have the strongest predicting impact on biological NM activity in the present dataset. Though the dataset is too small with respect to the number of NMs studied and the applicability domain is expected to be very limited due to the fact that only few material classes were covered, our study demonstrates how machine learning and feature selection methods can be implemented for identifying the most relevant physico-chemical NM properties with respect to toxicity. We suggest that once the most relevant properties have been detected in a model built on a sufficient number of different NMs and across multiple NM classes, they should obtain special emphasis in future grouping approaches.Peer Reviewe

Intelligent rooftop greenhouses and green skyline cities

The paper proposes a new concept of green building, able to oppose the global warming, the Intelligent Rooftop Greenhouse iRTG, as a development of the Integrated Rooftop Greenhouse IRTG. Our approach is to re­place conventional roofs with IRTGs, which are constructively con­nected with the interior of the building by flows of energy, gazes (mainly O2 enriched air from RTG to building and CO2 enriched air from build­ing to RTG) and water in order to improve the building’s metabolism. A tight human-plant sym­biosis is created such way. iRTGs perfect this architecture by actively controlling the energy, gazes and water flows, by collecting the available renewable energy resources (geothermal, sun, wind) and by adding Internet of Things IOT features to the system, in order to connect it to a surrounding Smart City. This way iRTGs may achieve an efficient integrated management of energy, gases and water, using just existing technologies: heat pumps (water to water for building’s basement and air to air for green­house), solar panels, IOT equipment, etc., controlled in a smart/intelligent manner. If a Smart City is composed mostly of iRTG buildings it becomes a Smart Green Skyline City, with low carbon foot­print and high carbon offset. The paper provides a mathematical iRTG model.Peer ReviewedPostprint (published version