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Nanomaterials And Nanoparticles Sources And Toxicity Pdf Download



Due to their unique physicochemical properties, graphene-family nanomaterials (GFNs) are widely used in many fields, especially in biomedical applications. Currently, many studies have investigated the biocompatibility and toxicity of GFNs in vivo and in intro. Generally, GFNs may exert different degrees of toxicity in animals or cell models by following with different administration routes and penetrating through physiological barriers, subsequently being distributed in tissues or located in cells, eventually being excreted out of the bodies. This review collects studies on the toxic effects of GFNs in several organs and cell models. We also point out that various factors determine the toxicity of GFNs including the lateral size, surface structure, functionalization, charge, impurities, aggregations, and corona effect ect. In addition, several typical mechanisms underlying GFN toxicity have been revealed, for instance, physical destruction, oxidative stress, DNA damage, inflammatory response, apoptosis, autophagy, and necrosis. In these mechanisms, (toll-like receptors-) TLR-, transforming growth factor β- (TGF-β-) and tumor necrosis factor-alpha (TNF-α) dependent-pathways are involved in the signalling pathway network, and oxidative stress plays a crucial role in these pathways. In this review, we summarize the available information on regulating factors and the mechanisms of GFNs toxicity, and propose some challenges and suggestions for further investigations of GFNs, with the aim of completing the toxicology mechanisms, and providing suggestions to improve the biological safety of GFNs and facilitate their wide application.




Nanomaterials And Nanoparticles Sources And Toxicity Pdf Download



The excretion and clearance of GFNs vary in different organs. In the lungs, observations indicated that NGO is drawn into and cleared by AMs, which might be eliminated from the sputum through mucociliary clearance or other ways [57], and 46.2 % of the intratracheally instilled FLG was excreted through the faeces 28 d after exposure [61]. In the liver, nanoparticles can be eliminated thorough the hepato-biliary pathway following the biliary duct into the duodenum [80]. In addition, PEGylated GNS that mainly accumulates in the liver and spleen can be gradually cleared, likely by both renal and faecal excretion. As recently reviewed, GO sheets larger than 200 nm are trapped by splenic physical filtration, but small sizes (approximately 8 nm) can penetrate the renal tubules into the urine and be rapidly removed without obvious toxicity [81]. The excretion paths of GFNs have not yet been clearly explained, but renal and faecal routes appear to be the main elimination routes for graphene.


The toxicity of GFNs in vitro is summarized in Table 2. Data on the cytotoxicity of graphene nanomaterials are contrasting, and varying characteristics influence the results. The mechanisms and influencing factors of toxicity need to be elucidated in detail.


To conclude, many studies have discussed representative mechanisms of GFNs toxicity involving four signalling pathways: TLRs, TGF-β, TNF-α and MAPKs. These four signalling pathways are correlative and cross-modulatory, making the inflammatory response, autophagy, apoptosis and other mechanisms independent and yet connected to each other. Additionally, oxidative stress appears to play the most important role in activating these signalling pathways. It has been reported that there are intersections of apoptosis, autophagy and necrosis in the studies of other nanomaterials toxicity, they inhibit or promote mutually in some conditions. However, the signalling pathways of GFNs toxicity investigated in papers to date are only a small part of an intricate web, and the network of signalling pathways needs to be explored in detail in the future.


Fourth, the administration route of GFNs plays a very important role in toxicity studies, and different delivery methods will result in different toxicological reactions [32, 53]. Thus, the route and period of exposure should be carefully chosen according to the aim of the study. Nasal drug delivery is often used to study the neurotoxicity of nanomaterials [230, 231], but this administration method has rarely been applied in the testing of GFNs toxicity. Toxicological studies of GFNs in the nervous system are rare, and the mechanism is unclear and needs to be studied further in the future. Recent toxicokinetic studies involving the absorption, distribution, metabolism, accumulation, and excretion of GFNs through different exposure routes have yielded some results but are far from sufficient to clarify the internal complex mechanisms. For instance, further studies are needed to understand the specific molecular mechanisms of GFNs passing through the physiological barriers and the amount of accumulation or the excretion period of GFNs in tissues. In addition, given the increased exposure of humans to GFNs, the assessment of systemic toxicity in the human body is indispensable in future studies.


Sixth, more specific signalling pathways in the mechanism of GFNs toxicity need to be discovered and elucidated. Currently, several typical toxicity mechanisms of GFNs have been illustrated and widely accepted, such as oxidative stress, apoptosis, and autophagy. However, these mechanisms have only been described in general terms, and the specific signalling pathways within these mechanisms need to be investigated in detail. The signalling pathways involved in the toxicity of other nanomaterials may also be relevant to the study of GFNs. Therefore, more signalling pathways should be detected in future research. For instance, nano-epigenetics has been considered in numerous studies of nanomaterials, which is also helpful in assessing the limited toxicity and side effects of GFNs. Recent studies have shown that GFNs could cause epigenetic and genomic changes that might stimulate physical toxicity and carcinogenicity [234]. GFNs have high surface areas, smooth continuous surfaces and bio-persistence, similar to the properties of tumorigenic solid-state implants. It is unknown whether GFNs have the potential to induce foreign body sarcomas, and definitive studies of tumour potentialities or risks of graphene should therefore be conducted as soon as possible.


Interestingly, the morphological parameters of nanoparticles (e.g., size and shape) can be modulated by varying the concentrations of chemicals and reaction conditions (e.g., temperature and pH). Nevertheless, if these synthesized nanomaterials are subject to the actual/specific applications, then they can suffer from the following limitation or challenges: (i) stability in hostile environment, (ii) lack of understanding in fundamental mechanism and modeling factors, (iii) bioaccumulation/toxicity features, (iv) expansive analysis requirements, (v) need for skilled operators, (vi) problem in devices assembling and structures, and (vii) recycle/reuse/regeneration. In true world, it is desirable that the properties, behavior, and types of nanomaterials should be improved to meet the aforementioned points. On the other hand, these limitations are opening new and great opportunities in this emerging field of research.


Green synthesis methodologies based on biological precursors depend on various reaction parameters such as solvent, temperature, pressure, and pH conditions (acidic, basic, or neutral). For the synthesis of metal/metal oxide nanoparticles, plant biodiversity has been broadly considered due to the availability of effective phytochemicals in various plant extracts, especially in leaves such as ketones, aldehydes, flavones, amides, terpenoids, carboxylic acids, phenols, and ascorbic acids. These components are capable of reducing metal salts into metal nanoparticles [11]. The basic features of such nanomaterials have been investigated for use in biomedical diagnostics, antimicrobials, catalysis, molecular sensing, optical imaging, and labelling of biological systems [12].


Yeasts are single-celled microorganisms present in eukaryotic cells. A total of 1500 yeast species have been identified [26]. Successful synthesis of nanoparticles/nanomaterials via yeast has been reported by numerous research groups. The biosynthesis of silver and gold nanoparticles by a silver-tolerant yeast strain and Saccharomyces cerevisiae broth has been reported. Many diverse species are employed for the preparation of innumerable metallic nanoparticles, as discussed in Table 1.


The need for hygienic and safe drinking water is increasing day by day. Considering this fact, the use of metal and metal oxide semiconductor nanomaterials for oxidizing toxic pollutants has become of great interest in recent material research fields [129,130,131]. In the nano regime, semiconductor nanomaterials have superior photocatalytic activity relative to the bulk materials. Metal oxide semiconductor nanoparticles (like ZnO, TiO2, SnO2, WO3, and CuO) have been applied preferentially for the photocatalytic activity of synthetic dyes [31, 132,133,134]. The merits of these nanophotocatalysts (e.g., ZnO and TiO2 nanoparticles) are ascribable to their high surface area to mass ratio to enhance the adsorption of organic pollutants. The surface energy of the nanoparticles increases due to the large number of surface reactive sites available on the nanoparticle surfaces. This leads to an increase in rate of contaminant removal at low concentrations. Consequently, a lower quantity of nanocatalyst will be required to treat polluted water relative to the bulk material [135,136,137,138]. Like metal oxide nanoparticles, metal nanoparticles also show enhanced photocatalytic degradation of various pollutant dyes; for example, silver nanoparticles synthesized from Z. armatum leaf extract were utilized for the degradation of various pollutant dyes [127] (Fig. 10).


Heavy metals (like Ni, Cu, Fe, Cr, Zn, Co, Cd, Pb, Cr, Hg, and Mn) are well-known for being pollutants in air, soil, and water. There are innumerable sources of heavy metal pollution such as mining waste, vehicle emissions, natural gas, paper, plastic, coal, and dye industries [139]. Some metals (like lead, copper, cadmium, and mercury ions) shows enhanced toxicity potential even at trace ppm levels [140, 141]. Therefore, the identification of toxic metals in the biological and aquatic environment has become a vital need for proper remedial processes [142,143,144]. Conventional techniques based on instrumental systems generally offer excellent sensitivity in multi-element analysis. However, experimental set ups to perform such analysis are highly expensive, time-consuming, skill-dependent, and non-portable.


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