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1.
Sci Total Environ ; 793: 148532, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34328986

RESUMO

Since graphene is currently incorporated into various consumer products and used in a variety of applications, determining the relationships between the physicochemical properties of graphene and its toxicity is critical for conducting environmental and health risk analyses. Data from the literature suggest that exposure to graphene may result in cytotoxicity. However, existing graphene toxicity data are complex and heterogeneous, making it difficult to conduct risk assessments. Here, we conducted a meta-analysis of published data on the cytotoxicity of graphene based on 792 publications, including 986 cell viability data points, 762 half maximal inhibitory concentration (IC50) data points, and 100 lactate dehydrogenase (LDH) release data points. Models to predict graphene cytotoxicity were then developed based on cell viability, IC50, and LDH release as toxicity endpoints using random forests learning algorithms. The most influential attributes influencing graphene cytotoxicity were revealed to be exposure dose and detection method for cell viability, diameter and surface modification for IC50, and detection method and organ source for LDH release. The meta-analysis produced three sets of key attributes for the three abovementioned toxicity endpoints that can be used in future studies of graphene toxicity. The findings indicate that rigorous data mining protocols can be combined with suitable machine learning tools to develop models with good predictive power and accuracy. The results also provide guidance for the design of safe graphene materials.


Assuntos
Grafite , Sobrevivência Celular , Mineração de Dados , Grafite/toxicidade , L-Lactato Desidrogenase , Aprendizado de Máquina
2.
Int J Mol Sci ; 22(14)2021 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-34299367

RESUMO

The scope of application of carbon nanomaterials in biomedical, environmental and industrial fields is recently substantially increasing. Since in vitro toxicity testing is the first essential step for any commercial usage, it is crucial to have a reliable method to analyze the potentially harmful effects of carbon nanomaterials. Even though researchers already reported the interference of carbon nanomaterials with common toxicity assays, there is still, unfortunately, a large number of studies that neglect this fact. In this study, we investigated interference of four bio-promising carbon nanomaterials (graphene acid (GA), cyanographene (GCN), graphitic carbon nitride (g-C3N4) and carbon dots (QCDs)) in commonly used LIVE/DEAD assay. When a standard procedure was applied, materials caused various types of interference. While positively charged g-C3N4 and QCDs induced false results through the creation of free agglomerates and intrinsic fluorescence properties, negatively charged GA and GCN led to false signals due to the complex quenching effect of the fluorescent dye of a LIVE/DEAD kit. Thus, we developed a new approach using a specific gating strategy based on additional controls that successfully overcame all types of interference and lead to reliable results in LIVE/DEAD assay. We suggest that the newly developed procedure should be a mandatory tool for all in vitro flow cytometry assays of any class of carbon nanomaterials.


Assuntos
Carbono/toxicidade , Nanoestruturas/toxicidade , Células Cultivadas , Citometria de Fluxo/métodos , Fluorescência , Corantes Fluorescentes/toxicidade , Grafite/toxicidade , Humanos , Compostos de Nitrogênio/toxicidade , Pontos Quânticos/toxicidade
3.
Environ Sci Technol ; 55(14): 9938-9948, 2021 07 20.
Artigo em Inglês | MEDLINE | ID: mdl-34232619

RESUMO

The application of graphene-based nanomaterials (GBNs) has attracted global attention in various fields, and understanding defense mechanisms against the phytotoxicity of GBNs is crucial for assessing their environmental risks and safe-by-design. However, the related information is lacking, especially for edible vegetable crops. In the present study, GBNs (0.25, 2.5, and 25 mg/kg plant fresh weight) were injected into the stems of pepper plants. The results showed that the plant defense was regulated by reducing the calcium content by 21.7-48.3%, intercellular CO2 concentration by 12.0-35.2%, transpiration rate by 8.7-40.2%, and stomatal conductance by 16.9-50.5%. The defense pathways of plants in response to stress were further verified by the downregulation of endocytosis and transmembrane transport proteins, leading to a decrease in the nanomaterial uptake. The phytohormone gibberellin and abscisic acid receptor PYL8 were upregulated, indicating the activation of defense systems. However, reduced graphene oxide and graphene oxide quantum dots trigger stronger oxidative stress (e.g., H2O2 and malondialdehyde) than graphene oxide in fruits due to the breakdown of antioxidant defense systems (e.g., cytochrome P450 86A22 and P450 77A1). Both nontargeted proteomics and metabolomics consistently demonstrated that the downregulation of carbohydrate and upregulation of amino acid metabolism were the main mechanisms underlying the phytotoxicity and defense mechanisms, respectively.


Assuntos
Grafite , Nanoestruturas , Mecanismos de Defesa , Grafite/toxicidade , Peróxido de Hidrogênio , Estresse Oxidativo
4.
J Hazard Mater ; 418: 126282, 2021 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-34111749

RESUMO

The wide application of carbon-based nanomaterials (CNMs) has resulted in the ubiquity of CNMs in the natural environment and they potentially impose adverse consequences on ecosystems and human health. In this study, we comprehensively evaluated and compared potential toxicological effects and mechanisms of seven CNMs in three representative types (carbon blacks, graphene nanoplatelets, and fullerenes), to elucidate the correlation between their physicochemical/structural properties and toxicity. We employed a recently-developed quantitative toxicogenomics-based toxicity testing system with GFP-fused yeast reporter library targeting main cellular stress response pathways, as well as conventional phenotype-based bioassays. The results revealed that DNA damage, oxidative stress, and protein stress were the major mechanisms of action for all the CNMs at sub-cytotoxic concentration levels. The molecular toxicity nature were concentration-dependent, and they exhibited both similarity within the same structural group and distinctiveness among different CNMs, evidencing the structure-driven toxicity of CNMs. The toxic potential based on toxicogenomics molecular endpoints revealed the remarkable impact of size and structure on the toxicity. Furthermore, the phenotypic endpoints derived from conventional phenotype-based bioassays correlated with quantitative molecular endpoints derived from the toxicogenomics assay, suggesting that the selected protein biomarkers captured the main cellular effects that are associated with phenotypic adverse outcomes.


Assuntos
Fulerenos , Grafite , Nanoestruturas , Nanotubos de Carbono , Ecossistema , Grafite/toxicidade , Humanos , Nanoestruturas/toxicidade
5.
Chemosphere ; 280: 130772, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34162089

RESUMO

The anthropogenic activities may lead to accumulation of graphene oxide (GO) pollution in the environment. Organisms exposed to chronic or multigenerational GO intoxication can present reproduction depletion. Vitellogenin (Vg) has been used as a parameter for evaluating female fertility due to its importance in embryo nutrition. In this study, we used a promising model organism, Acheta domesticus, which was intoxicated with GO in food for three generations. The aim of the study was to investigate the process of Vg synthesis in crickets depending on the exposure time, GO concentration, and age of the females. The results revealed that chronic GO intoxication had adverse effects on the Vg expression pattern. The 1st generation of insects showing low Vg expression was most affected. The 2nd generation of A. domesticus presented a high Vg expression. The last investigated generation seemed to cope with stress caused by GO, and the Vg expression was balanced. We suggest that the epigenetic mechanisms may play a role in the information transfer to the next generations on how to react to the risk factor and keep reproduction at a high rate. We suspect that chronic GO intoxication can disturb the regular formation of the Vg quaternary structure, resulting in consequences for developing an embryo.


Assuntos
Grafite , Vitelogeninas , Feminino , Grafite/toxicidade , Humanos , Proteômica , Reprodução , Vitelogeninas/genética
6.
Int J Mol Sci ; 22(10)2021 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-34065593

RESUMO

Interest in graphene oxide nature and potential applications (especially nanocarriers) has resulted in numerous studies, but the results do not lead to clear conclusions. In this paper, graphene oxide is obtained by multiple synthesis methods and generally characterized. The mechanism of GO interaction with the organism is hard to summarize due to its high chemical activity and variability during the synthesis process and in biological buffers' environments. When assessing the biocompatibility of GO, it is necessary to take into account many factors derived from nanoparticles (structure, morphology, chemical composition) and the organism (species, defense mechanisms, adaptation). This research aims to determine and compare the in vivo toxicity potential of GO samples from various manufacturers. Each GO sample is analyzed in two concentrations and applied with food. The physiological reactions of an easy model Acheta domesticus (cell viability, apoptosis, oxidative defense, DNA damage) during ten-day lasting exposure were observed. This study emphasizes the variability of the GO nature and complements the biocompatibility aspect, especially in the context of various GO-based experimental models. Changes in the cell biomarkers are discussed in light of detailed physicochemical analysis.


Assuntos
Materiais Biocompatíveis/química , Materiais Biocompatíveis/toxicidade , Grafite/química , Grafite/toxicidade , Animais , Apoptose/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Dano ao DNA/efeitos dos fármacos , Gryllidae/efeitos dos fármacos , Nanopartículas/química , Nanopartículas/toxicidade , Oxirredução/efeitos dos fármacos , Óxidos/metabolismo
7.
Arch Biochem Biophys ; 708: 108940, 2021 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-34058149

RESUMO

Nanomaterials, such as graphene oxide (GO), are increasingly being investigated for their suitability in biomedical applications. Tubulin is the key molecule for the formation of microtubules crucial for cellular function and proliferation, and as such an appealing target for developing anticancer drug. Here we employ biophysical techniques to study the effect of GO on tubulin structure and how the changes affect the tubulin/microtubule assembly. GO disrupts the structural integrity of the protein, with consequent retardation of tubulin polymerization. Investigating the anticancer potential of GO, we found that it is more toxic to human colon cancer cells (HCT116), as compared to human embryonic kidney epithelial cells (HEK293). Immunocytochemistry indicated the disruption of microtubule assembly in HCT116 cells. GO arrested cells in the S phase with increased accumulation in Sub-G1 population of cell cycle, inducing apoptosis by generating reactive oxygen species (ROS) in a dose- and time-dependent manner. GO inhibited microtubule formation by intervening into the polymerization of tubulin heterodimers both in vitro and ex vivo, resulting in growth arrest at the S phase and ROS induced apoptosis of HCT116 colorectal carcinoma cells. There was no significant harm to the HEK293 kidney epithelial cells used as control. Our report of pristine GO causing ROS-induced apoptosis of cancer cells and inhibition of tubulin-microtubule assembly can be of interest in cancer therapeutics and nanomedicine.


Assuntos
Neoplasias Colorretais/patologia , Grafite/toxicidade , Microtúbulos/efeitos dos fármacos , Ciclo Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Células HCT116 , Humanos , Microtúbulos/metabolismo , Compostos de Organossilício , Multimerização Proteica/efeitos dos fármacos , Estrutura Quaternária de Proteína/efeitos dos fármacos , Compostos de Amônio Quaternário , Tubulina (Proteína)/química
8.
J Hazard Mater ; 417: 125959, 2021 09 05.
Artigo em Inglês | MEDLINE | ID: mdl-33990041

RESUMO

Carbon nanomaterials (CNMs) provide an effective solution and a novel advancement for wastewater treatment. In this review, a total of 3823 bibliographic records derived from recent 10 years are visualized based on scientometric analysis. The results indicate metal-free CNMs-mediated advanced oxidation processes (AOPs) might be a motive force to develop CNMs application for wastewater treatment; however, corresponding evaluations of aquatic toxicity still lack sufficient attention. Therefore, recent breakthroughs and topical innovations related to prevalent wastewater treatment technologies (i.e., adsorption, catalysis and membrane separation) using three typical dimensional CNMs (nanodiamonds, carbon nanotubes, and graphene-based nanomaterials) are comprehensively summarized in-depth, along with a compendious introduction to some novel techniques (e.g., computational simulation) for identifying reaction mechanisms. Then, current research focusing on CNMs-associated aquatic toxicity is discussed thoroughly, mainly demonstrating: (1) the adverse effects on aquatic organisms should not be overlooked prior to large-scale CNMs application; (2) divergent consequences can be further reduced if the ecological niche of aquatic organisms is emphasized; and (3) further investigations on joint toxicity can provide greater beneficial insight into realistic exposure scenarios. Finally, ongoing challenges and developmental directions of CNMs-based wastewater treatment and evaluation of its aquatic toxicity are pinpointed and shaped in terms of future research.


Assuntos
Grafite , Nanoestruturas , Nanotubos de Carbono , Purificação da Água , Organismos Aquáticos , Grafite/toxicidade , Nanoestruturas/toxicidade , Nanotubos de Carbono/toxicidade
9.
J Hazard Mater ; 417: 125958, 2021 09 05.
Artigo em Inglês | MEDLINE | ID: mdl-34020354

RESUMO

The extensive use of graphene oxide (GO) results in its inevitable entry into the environment, raising risks to the environment, especially the ecological risks when coexisting with other contaminants. Nevertheless, how GO affects the biological behavior of Cd in plants remains poorly understood. Here, we report that the transcript levels of Cd transporters, including OsIRT1, OsIRT2, OsNramp1, OsNramp5, and OsHMA2, were decreased by 56-96% in Cd-stressed rice seedlings with exposure to 400 mg L-1 GO compared with those without GO exposure. The in situ non-invasive microelectrodes test revealed that GO clearly reduced the net Cd influx of rice roots. Thus, GO exposure decreased the level of Cd in rice seedlings by approximately 60%, compared with the GO-free condition. However, the analyses of biomass, chlorophyll fluorescence parameters and Evans blue staining, indicated that GO had adverse effects on the robustness of plants under the Cd co-contaminated condition. Taken together, although GO reduced the accumulation of Cd in rice seedlings, it still negatively affected plant growth. Therefore, the positive and negative impacts of GO on crop production are of concern. Our findings provide new information for establishing a wider phytotoxicity evaluation system for the safe manufacture and use of GO.


Assuntos
Grafite , Oryza , Cádmio/toxicidade , Grafite/toxicidade , Raízes de Plantas , Plântula
10.
Chemosphere ; 281: 130739, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34004516

RESUMO

Recent advances in the field of nanotechnology contributed to the increasing use of nanomaterials in the engineering, health and biological sectors. Graphene oxide (GO) has great potentials as it could be fine-tuned to be adapted into various applications, especially in the electrical, electronic, industrial and clinical fields. One of the important applications of GO is its use as an antibacterial material due to its promising activity against a broad range of bacteria. However, our understanding of the mechanism of action of GO towards bacteria is still lacking and is often less described. Therefore, a comprehensive overview of bactericidal mechanistic actions of GO and the roles of physicochemical factors including size, aggregation, functionalization and adsorption behavior contributing to its antibacterial activities are described in this review. As the use of GO is expected to increase exponentially in the health sector, the cytotoxicity of GO among the cell lines is also discussed. Thus, this review emphasizes the physicochemical characteristics of GO that can be tailored for optimal antibacterial properties that is of importance to the health industry.


Assuntos
Grafite , Nanoestruturas , Antibacterianos/toxicidade , Bactérias , Grafite/toxicidade , Óxidos/toxicidade
11.
Chemosphere ; 281: 130901, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34023764

RESUMO

The interest for graphene-based nanomaterials (GBMs) is growing worldwide as their properties allow the development of new innovative applications. In parallel, concerns are increasing about their potential adverse effects on the environment are increasing. The available data concerning the potential risk associated to exposure of aquatic organisms to these GBMs are still limited and little is known regarding their endocrine disruption potential. In the present study, the endocrine disruption potential of graphene oxide (GO) and reduced graphene oxide (rGO) was assessed using a T3-induced amphibian metamorphosis assay. The results indicated that GBMs potentiate the effects of exogenous T3 with a more marked effect of GO compared to rGO. T3 quantifications in the exposure media indicated adsorption of the hormone on GBMs, increasing its bioavailability for organisms because GBMs are accumulated in the gut and the gills of these amphibians. This study highlights that the tested GBMs do not disrupt the thyroid pathway in amphibians but indicates that adsorption properties of these nanomaterials may increase the bioavailability and the toxicity of other pollutants.


Assuntos
Grafite , Animais , Grafite/toxicidade , Metamorfose Biológica , Tri-Iodotironina , Xenopus laevis
12.
Ecotoxicol Environ Saf ; 220: 112348, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34015633

RESUMO

The phytotoxicity of nanoparticles has attracted considerable interest, given the broad applications of nanomaterials in different fields. Alfalfa (Medicago sativa L.) is a major forage crop grown worldwide with a high protein content. The molecular regulation mechanisms involved in nanomaterial-treated alfalfa were examined in this research. In our lab, 18 cDNA libraries of Golden Empress (GE) and Bara 310SC (SC) under control (CK), middle (10 g kg-1)- and high (20 g kg-1)-graphene stress treatments were constructed in 2019. All clean reads were matched to the reference Medicago_truncatula genome, the mapping ratio was higher than 50%, and a total of 3946 differentially expressed genes (DEGs) were obtained. The number of DEGs that reflect transcriptional activity is proportional to the degree of stress. For example, 1241/610 and 1794/1422 DEGs were identified as significant in the leaves of GE/SC under mid- and high-graphene treatment, respectively. Furthermore, GO analysis of the DEGs annotated in some significant biochemical process terms included 'response to abiotic stimulus', 'oxidation-reduction process', 'protein kinase activity', and 'oxidoreductase activity'. KEGG pathway analysis of the DEGs revealed strongly mediated graphene-responsive genes in alfalfa mainly linked to the 'biosynthesis of amino acids', 'isoflavonoid biosynthesis', 'linoleic acid metabolism', and 'phenylpropanoid biosynthesis' pathways. In addition, hundreds of DEGs, including photosynthetic, antioxidant enzyme, nitrogen metabolism, and metabolic sucrose and starch genes, have been identified as potentially involved in the response to graphene. Physiological findings revealed that enzymes related to the metabolism of nitrogen play a crucial role in the adaptation of graphene stress to alfalfa. Ultimately, in response to graphene stress, a preliminary regulatory mechanism was proposed for the self-protective mechanism of alfalfa, which helps to explain the phytotoxicity of the molecular mechanism of nanoparticle-treated crops.


Assuntos
Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Genes de Plantas/efeitos dos fármacos , Grafite/toxicidade , Medicago sativa/efeitos dos fármacos , Nanopartículas/toxicidade , Transcriptoma/efeitos dos fármacos , Medicago sativa/metabolismo , Folhas de Planta/efeitos dos fármacos , Folhas de Planta/metabolismo
13.
Chemosphere ; 277: 130160, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33794434

RESUMO

Advanced investigations on the use of graphene based nanomaterials have highlighted the capacity of these materials for wastewater treatment. Research on this topic revealed the efficiency of the nanocomposite synthetized by graphene oxide functionalized with polyethyleneimine (GO-PEI) to adsorb mercury (Hg) from contaminated seawater. However, information on the environmental risks associated with these approaches are still lacking. The focus of this study was to evaluate the effects of Hg in contaminated seawater and seawater remediated by GO-PEI, using the species Ruditapes philippinarum, maintained at two different warming scenarios: control (17 °C) and increased (22 °C) temperatures. The results obtained showed that organisms exposed to non-contaminated and remediated seawaters at control temperature presented similar biological patterns, with no considerable differences expressed in terms of biochemical and histopathological alterations. Moreover, the present findings revealed increased toxicological effects in clams under remediated seawater at 22 °C in comparison to those subjected to the equivalent treatment at 17 °C. These results confirm the capability of GO-PEI to adsorb Hg from water with no noticeable toxic effects, although temperature could alter the responses of mussels to remediated seawater. These materials seem to be a promise eco-friendly approach to remediate wastewater, with low toxicity evidenced by remediated seawater and high regenerative capacity of this nanomaterial, keeping its high removal performance after successive sorption-desorption cycles.


Assuntos
Bivalves , Grafite , Mercúrio , Nanocompostos , Poluentes Químicos da Água , Animais , Grafite/toxicidade , Laboratórios , Mercúrio/toxicidade , Nanocompostos/toxicidade , Água do Mar , Água , Poluentes Químicos da Água/análise , Poluentes Químicos da Água/toxicidade
14.
Chemosphere ; 278: 130421, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33839394

RESUMO

Graphene oxide (GO) is a promising and strategic carbon-based nanomaterial for innovative and disruptive technologies. It is therefore essential to address its environmental health and safety aspects. In this work, we evaluated the chemical degradation of graphene oxide by sodium hypochlorite (NaClO, bleach water) and its consequences over toxicity, on the nematode Caenorhabditis elegans. The morphological, chemical, and structural properties of GO and its degraded product, termed NaClO-GO, were characterized, exploring an integrated approach. After the chemical degradation of GO at room temperature, its flake size was reduced from 156 to 29 nm, while NaClO-GO showed changes in UV-vis absorption, and an increase in the amount of oxygenated surface groups, which dramatically improved its colloidal stability in moderately hard reconstituted water (EPA medium). Acute and chronic exposure endpoints (survival, growth, fertility, and reproduction) were monitored to evaluate material toxicities. NaClO-GO presented lower toxicity at all endpoints. For example, an increase of over 100% in nematode survival was verified for the degraded material when compared to GO at 10 mg L-1. Additionally, enhanced dark-field hyperspectral microscopy confirmed the oral uptake of both materials by C. elegans. Finally, this work represents a new contribution toward a better understanding of the links between the transformation of graphene-based materials and nanotoxicity effects (mitigation), which is mandatory for the safety improvements that are required to maximize nanotechnological benefits to society.


Assuntos
Grafite , Nanoestruturas , Animais , Caenorhabditis elegans , Grafite/toxicidade , Nanoestruturas/toxicidade , Óxidos/toxicidade , Hipoclorito de Sódio/toxicidade
15.
Environ Sci Pollut Res Int ; 28(26): 34664-34675, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33656705

RESUMO

Graphene-based nanomaterials (GBNs) have been widely used in various fields nowadays. However, they are reported to be highly toxic to some aquatic organisms. However, the multi-organ toxicity caused by pristine graphene (pG) and graphene oxide (GO) to the developing zebrafish (Danio rerio) larvae or juvenile and the underlying mechanisms is not fully known. Therefore, in the present study, the effect of pG and GO with environmental concentrations (0, 5, 10, 15, 20, and 25 µg/L of pG; 0, 0.1, 0.2, 0.3, and 0.4 mg/mL of GO) on multi-organ system in developing zebrafish larvae was experimentally assessed. The pG and GO were found to accumulate in the brain tissue that also caused significant changes in the heart beat and survival rate. The sizes of hepatocytes were reduced. Altered axonal integrity, affecting axon length and pattern in "Tg(mbp:eGFP) transgenic lines" was also observed. In addition, the results indicated pathological effects in major organs and with disrupted mitochondrial structure was quite obvious. The pG and GO bioaccumulation leads to multi organ toxicity in zebrafish larvae. In future, the existence of the current study can be extrapolated to other aquatic system in general and in particularly to humans.


Assuntos
Grafite , Poluentes Químicos da Água , Animais , Embrião não Mamífero , Grafite/toxicidade , Humanos , Larva , Poluentes Químicos da Água/toxicidade , Peixe-Zebra
16.
J Environ Sci Health B ; 56(4): 333-356, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33760696

RESUMO

With wider use of graphene-based materials and other two-dimensional (2 D) materials in various fields, including electronics, composites, biomedicine, etc., 2 D materials can trigger undesired effects at cellular, tissue and organ level. Macrophages can be found in many organs. They are one of the most important cells in the immune system and they are relevant in the study of nanomaterials as they phagocytose them. Nanomaterials have multi-faceted effects on phagocytic immune cells like macrophages, showing signs of inflammation in the form of pro-inflammatory cytokine or reactive oxidation species production, or upregulation of activation markers due to the presence of these foreign bodies. This review is catered to researchers interested in the potential impact and toxicity of 2 D materials, particularly in macrophages, focusing on few-layer graphene, graphene oxide, graphene quantum dots, as well as other promising 2 D materials containing molybdenum, manganese, boron, phosphorus and tungsten. We describe applications relevant to the growing area of 2 D materials research, and the possible risks of ions and molecules used in the production of these promising 2 D materials, or those produced by the degradation and dissolution of 2 D materials.


Assuntos
Macrófagos/efeitos dos fármacos , Nanoestruturas/química , Nanoestruturas/toxicidade , Animais , Citocinas/metabolismo , Grafite/química , Grafite/toxicidade , Humanos , Macrófagos/patologia , Macrófagos/fisiologia , Fósforo/química , Pontos Quânticos/química , Pontos Quânticos/toxicidade
17.
J Biomed Nanotechnol ; 17(1): 131-148, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-33653502

RESUMO

Graphene, including graphene quantum dots, its oxide and unoxidized forms (pure graphene) have several properties, like fluorescence, electrical conductivity, theoretical surface area, low toxicity, and high biocompatibility. In this study, we evaluated genotoxicity (in silico analysis using the functional density theory-FDT), cytotoxicity (human glioblastoma cell line), in vivo pharmacokinetics, in vivo impact on microcirculation and cell internalization assay. It was also radiolabeled with lutetium 177 (177Lu), a beta emitter radioisotope to explore its therapeutic use as nanodrug. Finally, the impact of its disposal in the environment was analyzed using ecotoxicological evaluation. FDT analysis demonstrated that graphene can construct covalent and non-covalent bonds with different nucleobases, and graphene oxide is responsible for generation of reactive oxygen species (ROS), corroborating its genotoxicity. On the other hand, non-cytotoxic effect on glioblastoma cells could be demonstrated. The pharmacokinetics analysis showed high plasmatic concentration and clearance. Topical application of 0.1 and 1 mg/kg of graphene nanoparticles on the hamster skinfold preparation did not show inflammatory effect. The cell internalization assay showed that 1-hour post contact with cells, graphene can cross the plasmatic membrane and accumulate in the cytoplasm. Radio labeling with 177Lu is possible and its use as therapeutic nanosystem is viable. Finally, the ecotoxicity analysis showed that A. silina exposed to graphene showed pronounced uptake and absorption in the nauplii gut and formation of ROS. The data obtained showed that although being formed exclusively of carbon and carbon-oxygen, graphene and graphene oxide respectively generate somewhat contradictory results and more studies should be performed to certify the safety use of this nanoplatform.


Assuntos
Grafite , Nanopartículas , Pontos Quânticos , Sobrevivência Celular , Grafite/toxicidade , Humanos , Óxidos , Espécies Reativas de Oxigênio
18.
J Hazard Mater ; 414: 125471, 2021 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-33647622

RESUMO

The biomedical applications of graphene-based nanomaterials (GBN) have significantly grown in the last years. Many of these applications suppose their intravenous exposure and, in this way, GBN could encounter blood cells triggering an immunological response of unknown effects. Consequently, understanding the relationships between GBN and the immune system response should be a prerequisite for its adequate use in biomedicine. In the present study, we have conducted a little explored ex vivo exposure method in order to study the complexity of the secretome given by the interactions between GBN and blood cells. Blood samples from different healthy donors were exposed to three different types of GBN widely used in the biomedical field. In this sense, graphene oxide (GO), graphene nanoplatelets (GNPs), graphene nanoribbons (GNRs) and a panel of 105 proteins representatives of the blood secretome were evaluated. The results show broad changes in both the cytokines number and the expression levels, with important changes in inflammatory response markers. Furthermore, the indirect soft-agar assay was used as a tool to unravel the global functional impact of the found secretome changes. Our results indicate that the GBN-induced altered secretome can modify the natural anchorage-independent growth capacity of HeLa cells, used as a model. As a conclusion, this study describes an innovative approach to study the potential harmful effects of GBN, providing relevant data to be considered in the biomedical context when GBN are planned to be used in patients.


Assuntos
Grafite , Nanoestruturas , Citocinas , Grafite/toxicidade , Células HeLa , Humanos , Sistema Imunitário , Nanoestruturas/toxicidade
19.
Chemosphere ; 276: 130015, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33690035

RESUMO

Novel products often have a multitude of nanomaterials embedded; likewise within many products graphite-based products are decorated with nano-zirconium oxide (nZrO2) because graphene is an ultrahigh conductive material whereas nZrO2 is for instance fire-retardant. As a consequence, the pristine/isolated nanoparticle has unique beneficial properties but it is no longer the only compound that needs to be considered in risk assessment. Data on joint toxicological implications are particularly important for the hazard assessment of multicomponent nanomaterials. Here, we investigated the mechanisms underlying the cytotoxicity induced by the co-occurrence of nZrO2 and two graphene nanomaterials including graphene nanoplatelets (GNPs) and reduced graphene oxide (RGO) to the freshwater algae Chlorella pyrenoidosa. Exposure to GNPs and/or RGO induced enhanced cytotoxicity of nZrO2 to the algae. Intracellular oxidative stress and cellular membrane functional changes in C. pyrenoidosa were the reason for the enhancement of toxicity induced by the binary mixtures of GNPs/RGO and nZrO2. Furthermore, mitochondria-generated ROS played a major role in regulating the treatment-induced cellular response in the algae. Observations of cellular superficial- and ultra-structures indicated that the binary mixtures provoked oxidative damage to the algal cells. RGO increased the cytotoxicity and the extent of cellular oxidative stress to a higher extent than GNPs. These findings provide new insights that are of use in the risk assessment of mixtures of graphene-based carbon nanomaterials and other ENPs, and fit the new ideas on product testing that respects the combination effects.


Assuntos
Chlorella , Grafite , Microalgas , Grafite/toxicidade , Óxidos/toxicidade
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