Novel magnetic iron oxide-dextran sulphate nanocomposites as potential anticoagulants: Investigating interactions with blood components and assessing cytotoxicity.

Examining the critical role of anticoagulants in medical practice, particularly their central function in preventing abnormal blood clotting, is of the utmost importance. However, the study of interactions between blood proteins and alternative anticoagulant nano-surfaces is still understood poorly. In this study, novel approach involving direct functionalisation of magnetic iron oxide nanoparticles (MNPs) as carriers with sulphated dextran (s-dext) is presented, with the aim of evaluating the potential of magnetically-responsive MNPs@s-dext as anticoagulants. The physicochemical characterisation of the synthesised MNPs@s-dext includes crystal structure analysis, morphology study, surface and electrokinetic properties, thermogravimetric analysis and magnetic properties` evaluation, which confirms the successful preparation of the nanocomposite with sulfonate groups. The anticoagulant potential of MNPs@s-dext was investigated using a standardised activated partial thromboplastin time (APTT) test and a modified APTT test with a quartz crystal microbalance with dissipation (QCM-D) which confirmed the anticoagulant effect. Time-resolved solid-liquid interactions between the MNPs@s-dext and model blood proteins bovine serum albumin and fibrinogen were also investigated, to gain insight into their hemocompatibility, and revealed protein-repellence of MNPs@s-dext against blood proteins. The study also addressed comprehensive cytotoxicity studies of prepared nanocomposites, and provided valuable insights into potential applicability of MNPs@s-dext as a promising magnetic anticoagulant in biomedical contexts.

Magnetic Nanoparticles: A Comprehensive Review from Synthesis to Biomedical Frontiers.

Nanotechnology has opened new doors of exploration, particularly in materials science and healthcare. Magnetic nanoparticles (MNP), the tiny magnets, because of their various properties, have the potential to bring about radical changes in the field of medicine. The distinctive surface chemistry, nontoxicity, biocompatibility, and, in particular, the inducible magnetic moment of magnetic materials has attracted a great deal of interest in morphological structures from a variety of scientific domains. This review presents a concise overview of MNPs and their crucial properties and synthesis routes. It also aims to highlight the continuous synthesis methods available for MNP production. In recent years, the use of computational methods for understanding the behavior of nanoparticles has been on the rise. Thus, we also discuss the numerical models developed to understand how magnetic nanoparticles can be used in magnetic hyperthermia and targeting the Circle of Wilis. With the increasing use of MNPs in biomedical applications, it becomes necessary to understand the mechanisms of toxicity, which are elucidated in this review. The review focuses on the biomedical applications of MNPs in drug delivery, theranostics, and MRI contrasting agents. We anticipate that this article will broaden the perspective on magnetic nanoparticles and help to understand their functionality and applicability better.

Interaction between polydopamine-based IONPs and human serum albumin (HSA): a spectroscopic analysis with cytotoxicity impact.

Iron oxide nanoparticles (IONPs) have been extensively explored in biomedicine, bio-sensing, hyperthermia, and drug/gene delivery, attributed to their versatile and tunable properties. However, owing to its numerous applications, the functionalization of IONPs with appropriate materials is in demand. To achieve optimal functionalization of IONPs, polydopamine (PDA) was utilized due to its ability to provide a superior functionalized surface, near-infrared light absorption, and adhesive nature to customize desired functionalized IONPs. This notion of involving PDA led to the successful synthesis of magnetite-PDA nanoparticles, where PDA is surface-coated on magnetite (Fe3O4@PDA). The Fe3O4@PDA nanoparticles were characterized using techniques like TEM, FESEM, PXRD, XPS, VSM, and FTIR, suggesting PDA's successful attachment with magnetite crystal structure retention. Human serum albumin (HSA), the predominant protein in blood plasma, interacts with the delivered nanoparticles. Therefore, we have employed various spectroscopic techniques, along with cytotoxicity, to inspect the effect of Fe3O4@PDA NPs on the stability and structure of HSA. The structural alterations were examined using circular dichroism (CD) and synchronous fluorescence spectroscopy (SFS). It has been observed that there are no structural perturbations in the secondary structure of the HSA protein after interaction with Fe3O4@PDA. Studies using steady-state fluorescence revealed that the inherent fluorescence intensities of HSA were suppressed after interaction with Fe3O4@PDA. In addition, temperature-dependent fluorescence measurements suggested that the type of quenching consists of both static and dynamic quenching simultaneously. A cytotoxicity study in Drosophila melanogaster larvae revealed no cytotoxic effects but did show a minor genotoxic effect only at higher concentrations.

Nanostructured Magnetic Particles for Removing Cyanotoxins: Assessing Effectiveness and Toxicity In Vitro.

The rise in cyanobacterial blooms due to eutrophication and climate change has increased cyanotoxin presence in water. Most current water treatment plants do not effectively remove these toxins, posing a potential risk to public health. This study introduces a water treatment approach using nanostructured beads containing magnetic nanoparticles (MNPs) for easy removal from liquid suspension, coated with different adsorbent materials to eliminate cyanotoxins. Thirteen particle types were produced using activated carbon, CMK-3 mesoporous carbon, graphene, chitosan, 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO)-oxidised cellulose nanofibers (TOCNF), esterified pectin, and calcined lignin as an adsorbent component. The particles' effectiveness for detoxification of microcystin-LR (MC-LR), cylindrospermopsin (CYN), and anatoxin-A (ATX-A) was assessed in an aqueous solution. Two particle compositions presented the best adsorption characteristics for the most common cyanotoxins. In the conditions tested, mesoporous carbon nanostructured particles, P1-CMK3, provide good removal of MC-LR and Merck-activated carbon nanostructured particles, P9-MAC, can remove ATX-A and CYN with high and fair efficacy, respectively. Additionally, in vitro toxicity of water treated with each particle type was evaluated in cultured cell lines, revealing no alteration of viability in human renal, neuronal, hepatic, and intestinal cells. Although further research is needed to fully characterise this new water treatment approach, it appears to be a safe, practical, and effective method for eliminating cyanotoxins from water.

Altered Morpho-Functional Features of Neurogenesis in Zebrafish Embryos Exposed to Non-Combustion-Derived Magnetite.

Neurogenesis is the process by which new brain cells are formed. This crucial event emerges during embryonic life and proceeds in adulthood, and it could be influenced by environmental pollution. Non-combustion-derived magnetite represents a portion of the coarse particulate matter (PM) contributing to air and water pollution in urban settings. Studies on humans have reported that magnetite and other iron oxides have significant damaging effects at a central level, where these particles accumulate and promote oxidative stress. Similarly, magnetite nanoparticles can cross the placenta and damage the embryo brain during development, but the impact on neurogenesis is still unknown. Furthermore, an abnormal Fe cation concentration in cells and tissues might promote reactive oxygen species (ROS) generation and has been associated with multiple neurodegenerative conditions. In the present study, we used zebrafish as an in vivo system to analyze the specific effects of magnetite on embryonic neurogenesis. First, we characterized magnetite using mineralogical and spectroscopic analyses. Embryos treated with magnetite at sub-lethal concentrations showed a dose-response increase in ROS in the brain, which was accompanied by a massive decrease in antioxidant genes (sod2, cat, gsr, and nrf2). In addition, a higher number of apoptotic cells was observed in embryos treated with magnetite. Next, interestingly, embryos exposed to magnetite displayed a decrease in neural staminal progenitors (nestin, sox2, and pcna markers) and a neuronal marker (elavl3). Finally, we observed significative increases in apoeb (specific microglia marker) and interleukin-1b (il1b), confirming a status of inflammation in the brain embryos treated with magnetite. Our study represents the very first in vivo evidence concerning the effects of magnetite on brain development.

Nano-sized polystyrene and magnetite collectively promote biofilm stability and resistance due to enhanced oxidative stress response.

Despite the growing prevalence of nanoplastics in drinking water distribution systems, the collective influence of nanoplastics and background nanoparticles on biofilm formation and microbial risks remains largely unexplored. Here, we demonstrate that nano-sized polystyrene modified with carboxyl groups (nPS) and background magnetite (nFe3O4) nanoparticles at environmentally relevant concentrations can collectively stimulate biofilm formation and prompt antibiotic resistance. Combined exposure of nPS and nFe3O4 by P. aeruginosa biofilm cells stimulated intracellular reactive oxidative species (ROS) production more significantly compared with individual exposure. The resultant upregulation of quorum sensing (QS) and c-di-GMP signaling pathways enhanced the biosynthesis of polysaccharides by 50 %- 66 % and increased biofilm biomass by 36 %- 40 % relative to unexposed control. Consistently, biofilm mechanical stability (measured as Young's modulus) increased by 7.2-9.1 folds, and chemical stress resistance (measured with chlorine disinfection) increased by 1.4-2.0 folds. For P. aeruginosa, the minimal inhibitory concentration of different antibiotics also increased by 1.1-2.5 folds after combined exposure. Moreover, at a microbial community-wide level, metagenomic analysis revealed that the combined exposure enhanced the multi-species biofilm's resistance to chlorine, enriched the opportunistic pathogenic bacteria, and promoted their virulence and antibiotic resistance. Overall, the enhanced formation of biofilms (that may harbor opportunistic pathogens) by nanoplastics and background nanoparticles is an overlooked phenomenon, which may jeopardize the microbial safety of drinking water distribution systems.

Magnetic carbon nanotubes modified with proteins and hydrophilic monomers: Cytocompatibility, in-vitro toxicity assays and permeation across biological interfaces.

Carbon nanotubes are promising materials for biomedical applications like delivery systems and tissue scaffolds. In this paper, magnetic carbon nanotubes (M-CNTs) covered with bovine serum albumin (M-CNTs-BSA) or functionalized with hydrophilic monomers (M-CNTs-HL) were synthesized, characterized, and evaluated concerning their interaction with Caco-2 cells. There is no comparison between these two types of functionalization, and this study aimed to verify their influence on the material's interaction with the cells. Different concentrations of the nanotubes were applied to investigate cytotoxicity, cell metabolism, oxidative stress, apoptosis, and capability to cross biomimetic barriers. The materials showed cytocompatibility up to 100 µg mL-1 and a hemolysis rate below 2 %. Nanotubes' suspensions were allowed to permeate Caco-2 monolayers for up to 8 h under the effect of the magnetic field. Magnetic nanoparticles associated with the nanotubes allowed estimation of permeation through the monolayers, with values ranging from 0.50 to 7.19 and 0.27 to 9.30 × 10-3 µg (equivalent to 0.43 to 6.22 and 0.23 to 9.54 × 10-2 % of the initially estimated mass of magnetic nanoparticles) for cells exposed and non-exposed to the magnets, respectively. Together, these results support that the developed materials are promising for applications in biomedical and biotechnological fields.

Impact of Fe3O4-porphyrin hybrid nanoparticles on wheat: Physiological and metabolic advance.

Iron-magnetic nanoparticles (Fe-NMPs) are widely used in environmental remediation, while porphyrin-based hybrid materials anchored to silica-coated Fe3O4-nanoparticles (Fe3O4-NPs) have been used for water disinfection purposes. To assess their safety on plants, especially concerning potential environmental release, it was investigated for the first time, the impact on plants of a silica-coated Fe3O4-NPs bearing a porphyrinic formulation (FORM) - FORM@NMP. Additionally, FORM alone and the magnetic nanoparticles without FORM anchored (NH2@NMP) were used for comparison. Wheat (Triticum aestivum L.) was chosen as a model species and was subjected to three environmentally relevant doses during germination and tiller development through root application. Morphological, physiological, and metabolic parameters were assessed. Despite a modest biomass decrease and alterations in membrane properties, no major impairments in germination or seedling development were observed. During tiller phase, both Fe3O4-NPs increased leaf length, and photosynthesis exhibited varied impacts: both Fe3O4-NPs and FORM alone increased pigments; only Fe3O4-NPs promoted gas exchange; all treatments improved the photochemical phase. Regarding oxidative stress, lipid peroxidation decreased in FORM and FORM@NMP, yet with increased O2-• in FORM@NMP; total flavonoids decreased in NH2@NMP and antioxidant enzymes declined across all materials. Phenolic profiling revealed a generalized trend towards a decrease in flavones. In conclusion, these nanoparticles can modulate wheat physiology/metabolism without apparently inducing phytotoxicity at low doses and during short-time exposure. ENVIRONMENTAL IMPLICATION: Iron-magnetic nanoparticles are widely used in environmental remediation and fertilization, besides of new applications continuously being developed, making them emerging contaminants. Soil is a major sink for these nanoparticles and their fate and potential environmental risks in ecosystems must be addressed to achieve more sustainable environmental applications. Furthermore, as the reuse of treated wastewater for agricultural irrigation is being claimed, it is of major importance to disclose the impact on crops of the nanoparticles used for wastewater decontamination, such as those proposed in this work.

Low toxicity of magnetite-based modified bionanocomposites with potential application for wastewater treatment: Evaluation in a zebrafish animal model.

In recent years, the escalating concerns surrounding environmental pollution and the need for sustainable wastewater treatment solutions have underscored the significance of developing technologies that can efficiently treat wastewater while also reducing negative ecological effects. In this context, our study aims to contribute to the advancement of sustainable technologies for wastewater treatment, by investigating the effects that bare magnetite nanoparticles and those functionalized with the enzyme laccase could have in an aquatic animal, zebrafish, at various life cycle stages. Exposure to magnetite nanoparticles shows some effects on embryo hatching, survival rates, or larval behavior at higher concentrations. For both treatments, the hatching percentages were close to 80% compared to 93% for the control group. At the end of the observations in larvae, survival in all the evaluated groups was higher than 90%. Additionally, we evaluated the accumulation of nanoparticles in various stages of zebrafish. We found that, although there was accumulation during embryonic stages, it did not affect normal development or subsequent hatching. Iron levels in different organs such as gills, muscles, gastrointestinal tract, and brain were also evaluated in adults. Animals treated with a mix of food and nanoparticles at 10 µg/mL (Food group) presented a higher concentration of iron accumulation in muscle, gastrointestinal tract, and gills compared to the untreated control group. Although iron levels increased depending on the dose and exposure method applied, they were not statistically significant from the control groups. Our findings suggest that bionanocomposites evaluated here can be considered safe for removal of contaminants in wastewater without toxic effects or detrimental accumulation fish's health.

Non-invasive methods of monitoring Fe3O4 magnetic nanoparticle toxicity in human liver HepaRG cells using impedance biosensing and Coherent anti-Stokes Raman spectroscopic (CARS) microscopy.

Functionalized nanoparticles have been developed for use in nanomedicines for treating life threatening diseases including various cancers. To ensure safe use of these new nanoscale reagents, various assays for biocompatibility or cytotoxicity in vitro using cell lines often serve as preliminary assessments prior to in vivo animal testing. However, many of these assays were designed for soluble, colourless materials and may not be suitable for coloured, non-transparent nanoparticles. Moreover, cell lines are not always representative of mammalian organs in vivo. In this work, we use non-invasive impedance sensing methods with organotypic human liver HepaRG cells as a model to test the toxicity of PEG-Fe3O4 magnetic nanoparticles. We also use Coherent anti-Stokes Raman Spectroscopic (CARS) microscopy to monitor the formation of lipid droplets as a parameter to the adverse effect on the HepaRG cell model. The results were also compared with two commercial testing kits (PrestoBlue and ATP) for cytotoxicity. The results suggested that the HepaRG cell model can be a more realistic model than commercial cell lines while use of impedance monitoring of Fe3O4 nanoparticles circumventing the uncertainties due to colour assays. These methods can play important roles for scientists driving towards the 3Rs principle - Replacement, Reduction and Refinement.

Genotoxicity and heating Performance of VxFe3-xO4 nanoparticles in Health applications.

The applications of magnetic nanoparticles (MNPs) as biocatalysts in different biomedical areas have been evolved very recently. One of the main challenges in this field is to design affective MNPs surfaces with catalytically active atomic centres, while producing minimal toxicological side effects on the hosting cell or tissues. MNPs of vanadium spinel ferrite (VFe2O4) are a promising material for mimicking the action of natural enzymes in degrading harmful substrates due to the presence of active V5+ centres. However, the toxicity of this material has not been yet studied in detail enough to grant biomedical safety. In this work, we have extensively measured the structural, compositional, and magnetic properties of a series of VxFe3-xO4 spinel ferrite MNPs to assess the surface composition and oxidation state of V atoms, and also performed systematic and extensive in vitro cytotoxicity and genotoxicity testing required to assess their safety in potential clinical applications. We could establish the presence of V5+ at the particle surface even in water-based colloidal samples at pH 7, as well as different amounts of V2+ and V3+ substitution at the A and B sites of the spinel structure. All samples showed large heating efficiency with Specific Loss Power values up to 400 W/g (H0 = 30 kA/m; f = 700 kHz). Samples analysed for safety in human hepatocellular carcinoma (HepG2) cell line with up to 24h of exposure showed that these MNPs did not induce major genomic abnormalities such as micronuclei, nuclear buds, or nucleoplasmic bridges (MNIs, NBUDs, and NPBs), nor did they cause DNA double-strand breaks (DSBs) or aneugenic effects-types of damage considered most harmful to cellular genetic material. The present study is an essential step towards the use of these type of nanomaterials in any biomedical or clinical application.

Comparative studies on the cytotoxic effects induced by iron oxide nanoparticles in cancerous and noncancerous human lung cells subjected to an alternating magnetic field.

The cytotoxic effects of water-based ferrofluids composed of iron oxide nanoparticles, including magnetite (Fe3O4) and maghemite (γ-Fe2O3), ranging from 15 to 100 nm, were examined on various lung cancer cells including adenocarcinomic human alveolar basal epithelial cells (A549), nonsmall lung squamous cell carcinoma (H1703), small cell lung cancer cells (DMS 114), and normal bronchial epithelial cells (BEAS-2B). The cytotoxic effect was evaluated both with and without exposure to an alternating magnetic field (AMF). The studies revealed that neither AMF nor iron oxide nanoparticles when tested individually, produced cytotoxic effects on either cancerous or noncancerous cells. However, when applied together, they led to a significant decrease in cell viability and proliferative capacity due to the enhanced effects of magnetic fluid hyperthermia (MFH). The most pronounced effects were found for maghemite (<50 nm) when subjected to an AMF. Notably, A549 cells exhibited the highest resistance to the proposed hyperthermia treatment. BEAS-2B cells demonstrated susceptibility to magnetized iron oxide nanoparticles, similar to the response observed in lung cancer cells. The studies provide evidence that MFH is a promising strategy as a standalone treatment for different types of lung cancer cells. Nevertheless, to prevent any MFH-triggered adverse effects on normal lung cells, targeted magnetic ferrofluids should be designed.

Airborne magnetite nanoparticles induced early vascular pathologies by disrupting lipid metabolism under high-fat dietary patterns.

Magnetite nanoparticles (MNPs) have been extensively detected in the atmospheric environment and implicated as a prominent threat to atherosclerosis, a chronic vascular inflammatory disease. Due to globalization and economic development, the dramatic shift in diet from traditional to high-fat dietary patterns aggravated atherosclerosis progression induced by environmental factors. However, limited knowledge is available regarding vascular risks and underlying mechanisms of airborne MNPs in high-risk populations with high-fat dietary habits. Herein, we demonstrated that MNPs exerted a proatherogenic effect under high-fat dietary patterns, leading to aortic wall thickening, elastic fiber disorganization, macrophage infiltration, and local inflammation. Based on the correlation analysis between MNPs and PM group, we identified that MNPs might be a key PM component in atherogenic toxicity. MNPs exposure disturbed the dynamic process of lipid metabolism, manifested as aortic lipid accumulation, dyslipidemia, and hepatic lipid metabolism disorder, which was modulated by the JAK-STAT pathway. Overall, these findings provide new insight into understanding the cardiovascular risks and mechanisms of MNPs among high-risk populations.

Reduced lysosomal activity and increased amyloid beta accumulation in silica-coated magnetic nanoparticles-treated microglia.

Nanoparticles have been used in neurological research in recent years because of their blood-brain barrier penetration activity. However, their potential neuronanotoxicity remains a concern. In particular, microglia, which are resident phagocytic cells, are mainly exposed to nanoparticles in the brain. We investigated the changes in lysosomal function in silica-coated magnetic nanoparticles containing rhodamine B isothiocyanate dye [MNPs@SiO2(RITC)]-treated BV2 murine microglial cells. In addition, we analyzed amyloid beta (Aß) accumulation and molecular changes through the integration of transcriptomics, proteomics, and metabolomics (triple-omics) analyses. Aß accumulation significantly increased in the 0.1 µg/µl MNPs@SiO2(RITC)-treated BV2 cells compared to the untreated control and 0.01 µg/µl MNPs@SiO2(RITC)-treated BV2 cells. Moreover, the MNPs@SiO2(RITC)-treated BV2 cells showed lysosomal swelling, a dose-dependent reduction in proteolytic activity, and an increase in lysosomal swelling- and autophagy-related protein levels. Moreover, proteasome activity decreased in the MNPs@SiO2(RITC)-treated BV2 cells, followed by a concomitant reduction in intracellular adenosine triphosphate (ATP). By employing triple-omics and a machine learning algorithm, we generated an integrated single molecular network including reactive oxygen species (ROS), autophagy, lysosomal storage disease, and amyloidosis. In silico analysis of the single triple omics network predicted an increase in ROS, suppression of autophagy, and aggravation of lysosomal storage disease and amyloidosis in the MNPs@SiO2(RITC)-treated BV2 cells. Aß accumulation and lysosomal swelling in the cells were alleviated by co-treatment with glutathione (GSH) and citrate. These findings suggest that MNPs@SiO2(RITC)-induced reduction in lysosomal activity and proteasomes can be recovered by GSH and citrate treatment. These results also highlight the relationship between nanotoxicity and Aß accumulation.

Biodistribution and histological analysis of iron oxide-dextran nanoparticles in wistar rats.

Iron oxide nanoparticles (IONP) are showing promise in many biomedical applications. One of these- magnetic hyperthermia- utilizes externally applied alternating magnetic fields and tumor-residing magnetic nanoparticles to generate localized therapeutic temperature elevations. Magnetic hyperthermia is approved in Europe to treat glioblastoma and is undergoing clinical assessment in the United States to treat prostate cancer. In this study, we performed biodistribution and histological analysis of a new IONP (RCL-01) in Wistar rats. These nanoparticles are currently undergoing clinical assessment in locally advanced pancreatic ductal adenocarcinoma to determine the feasibility of magnetic hyperthermia treatment in this disease. The study presented here aimed to determine the fate of these nanoparticles in vivo and whether this results in organ damage. Wistar rats were injected intravenously with relatively high doses of IONP (30 mgFe/kg, 45 mgFe/kg and 60 mgFe/kg) and compared to a vehicle control to determine the accumulation of iron in organs and whether this resulted in histological changes in these tissues. Dose-dependent increases of iron were observed in the liver, spleen and lungs of IONP-treated animals at 7 days postinjection; however, this did not result in significant histological changes in these tissues. Immunofluorescent imaging determined these nanoparticles are internalized by macrophages in tissue, suggesting they are readily phagocytosed by the reticuloendothelial system for eventual recycling. Notably, no changes in iron or dextran staining were found in the kidneys across all treatment groups, providing evidence for potential renal clearance.

Comparative in vitro and in vivo Evaluation of Different Iron Oxide-Based Contrast Agents to Promote Clinical Translation in Compliance with Patient Safety.

Introduction: One of the major challenges in the clinical translation of nanoparticles is the development of formulations combining favorable efficacy and optimal safety. In the past, iron oxide nanoparticles have been introduced as an alternative for gadolinium-containing contrast agents; however, candidates available at the time were not free from adverse effects. Methods: Following the development of a potent iron oxide-based contrast agent SPIONDex, we now performed a systematic comparison of this formulation with the conventional contrast agent ferucarbotran and with ferumoxytol, taking into consideration their physicochemical characteristics, bio- and hemocompatibility in vitro and in vivo, as well as their liver imaging properties in rats. Results: The results demonstrated superior in vitro cyto-, hemo- and immunocompatibility of SPIONDex in comparison to the other two formulations. Intravenous administration of ferucarbotran or ferumoxytol induced strong complement activation-related pseudoallergy in pigs. In contrast, SPIONDex did not elicit any hypersensitivity reactions in the experimental animals. In a rat model, comparable liver imaging properties, but a faster clearance was demonstrated for SPIONDex. Conclusion: The results indicate that SPIONDex possess an exceptional safety compared to the other two formulations, making them a promising candidate for further clinical translation.

Influence of PEG Chain Length of Functionalized Magnetic Nanoparticles on the Cytocompatibility and Immune Competence of Primary Murine Macrophages and Dendritic Cells.

A major drawback of nanoparticles (NPs) for biomedical applications is their preferential phagocytosis in immune cells, which can be avoided by surface modifications like PEGylation. Nevertheless, examinations of different polyethylene glycol (PEG) chain lengths on the competence of immune cells as well as possible immunotoxic effects are still sparse. Therefore, primary murine macrophages and dendritic cells were generated and incubated with magnetic nanoporous silica nanoparticles (MNPSNPs) modified with different mPEG chains (2 kDa, 5 kDa, and 10 kDa). Cytotoxicity, cytokine release, and the formation of reactive oxygen species (ROS) were determined. Immune competence of both cell types was examined and uptake of MNPSNPs into macrophages was visualized. Concentrations up to 150 µg/mL MNPSNPs showed no effects on the metabolic activity or immune competence of both cell types. However, ROS significantly increased in macrophages incubated with larger PEG chains, while the concentration of cytokines (TNF-α and IL-6) did not indicate a proinflammatory process. Investigations on the uptake of MNPSNPs revealed no differences in the onset of internalization and the intensity of intracellular fluorescence. The study gives no indication for an immunotoxic effect of PEGylated MNPSNPs. Nevertheless, there is still a need for optimization regarding their internalization to ensure an efficient drug delivery.

Removal of lithium from aqueous solutions by solid-phase extraction using sawdust loaded with magnetite nanoparticles and study of apoptosis, MDA and 8-OHdG caused by lithium toxicity in fish brain.

Lithium, which has a high industrial value, is an environmental pollutant of concern to those who work with lithium in industry as well as to the general public. Biological parameters such as MDA, 8-OHdG, apoptosis (caspase-3), and acetylcholinesterase (AChE) were studied to determine the toxic effects on the brain tissue of the model organism (Carassius auratus) exposed to high dose lithium. According to the results obtained, it was found that lithium exposure caused oxidative stress with an increase in MDA level over time and, accordingly, DNA damage and apoptosis occured in brain tissue. It was also found that a decrease in AChE activity was observed, and the high levels of MDA, 8-OHdG, and caspase-3 activity obtained in brain tissue supported this result. The solid phase extraction (SPE) method was used to effectively remove lithium, which has unfavorable effects on living organisms, from aqueous solutions. In this method, a sawdust loaded with magnetite nanoparticles (MNLS) was prepared as an adsorbent for solid phase extraction by a simple method, and it was characterized. Optimal conditions for the SPE process were defined and it was found that lithium could be removed from solution onto the MNLS surface with a high yield of about 96%. The results of the study are crucial for proposing a simple and applicable high performance method.

Functionalized Magnetite Nanoparticles: Characterization, Bioeffects, and Role of Reactive Oxygen Species in Unicellular and Enzymatic Systems.

The current study evaluates the role of reactive oxygen species (ROS) in bioeffects of magnetite nanoparticles (MNPs), such as bare (Fe3O4), humic acids (Fe3O4-HA), and 3-aminopropyltriethoxysilane (Fe3O4-APTES) modified MNPs. Mössbauer spectroscopy was used to identify the local surrounding for Fe atom/ions and the depth of modification for MNPs. It was found that the Fe3O4-HA MNPs contain the smallest, whereas the Fe3O4-APTES MNPs contain the largest amount of Fe2+ ions. Bioluminescent cellular and enzymatic assays were applied to monitor the toxicity and anti-(pro-)oxidant activity of MNPs. The contents of ROS were determined by a chemiluminescence luminol assay evaluating the correlations with toxicity/anti-(pro-)oxidant coefficients. Toxic effects of modified MNPs were found at higher concentrations (>10−2 g/L); they were related to ROS storage in bacterial suspensions. MNPs stimulated ROS production by the bacteria in a wide concentration range (10−15−1 g/L). Under the conditions of model oxidative stress and higher concentrations of MNPs (>10−4 g/L), the bacterial bioassay revealed prooxidant activity of all three MNP types, with corresponding decay of ROS content. Bioluminescence enzymatic assay did not show any sensitivity to MNPs, with negligible change in ROS content. The results clearly indicate that cell-membrane processes are responsible for the bioeffects and bacterial ROS generation, confirming the ferroptosis phenomenon based on iron-initiated cell-membrane lipid peroxidation.

Synthesis and Characterization of a Biocompatible Nanoplatform Based on Silica-Embedded SPIONs Functionalized with Polydopamine.

Superparamagnetic iron oxide nanoparticles (SPIONs) have gained increasing interest in nanomedicine, but most of those that have entered the clinical trials have been withdrawn due to toxicity concerns. Therefore, there is an urgent need to design low-risk and biocompatible SPION formulations. In this work, we present an original safe-by-design nanoplatform made of silica nanoparticles loaded with SPIONs and decorated with polydopamine (SPIONs@SiO2-PDA) and the study of its biocompatibility performance by an ad hoc thorough in vitro to in vivo nanotoxicological methodology. The results indicate that the SPIONs@SiO2-PDA have excellent colloidal stability in serum-supplemented culture media, even after long-term (24 h) exposure, showing no cytotoxic or genotoxic effects in vitro and ex vivo. Physiological responses, evaluated in vivo using Caenorhabditis elegans as the animal model, showed no impact on fertility and embryonic viability, induction of an oxidative stress response, and a mild impact on animal locomotion. These tests indicate that the synergistic combination of the silica matrix and PDA coating we developed effectively protects the SPIONs, providing enhanced colloidal stability and excellent biocompatibility.