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Toward safer multi-walled carbon nanotube design: Establishing a statistical model that relates surface charge and embryonic zebrafish mortality
Nanotoxicology
Abstract
Abstract Given the increased utility and lack of consensus regarding carbon nanotube (CNT) environmental and human health hazards, there is a growing demand for guidelines that inform safer CNT design. In this study, the zebrafish (Danio rerio) model is utilized as a stable, sensitive biological system to evaluate the bioactivity of systematically modified and comprehensively characterized multi-walled carbon nanotubes (MWNTs). MWNTs were treated with strong acid to introduce oxygen functional groups, which were then systematically thermally reduced and removed using an inert temperature treatment. While 25 phenotypic endpoints were evaluated at 24 and 120 hours post-fertilization (hpf), high mortality at 24 hpf prevented further resolution of the mode of toxicity leading to mortality. Advanced multivariate statistical methods are employed to establish a model that identifies those MWNT physicochemical properties that best estimate the probability of observing an adverse outcome. The physicochemical properties considered in this study include surface charge, percent surface oxygen, dispersed aggregate size and morphology and electrochemical activity. Of the five physicochemical properties, surface charge, quantified as the point of zero charge (PZC), was determined as the best predictor of mortality at 24 hpf. From a design perspective, the identification of this property-hazard relationship establishes a foundation for the development of design guidelines for MWNTs with reduced hazard.
... First, there is no consensus on MWCNT toxicity mechanism(s) toward zebrafish and other aquatic species, which could lead to the unintentional (re)design of MWCNTs that may be more hazardous than anticipated. While oxidative stress induced by carbonaceous nanomaterials has been hypothesized as the main mechanism driving toxicity towards aquatic species [32e34], physicochemical properties such as length [35], surface functionality [36,37], or the surface charge of the MWCNTs [38] have also been related to toxic responses. While these have, in most cases, been individually considered, few studies have looked at these properties simultaneously and comprehensively. ...
... Specifically, it has been shown that the various physicochemical properties of carbon nanotubes can impact their colloidal behavior and dispersibility in aqueous media containing salts. For example, an increase in oxygen moieties, such as hydroxyl groups, on the surface of both single-and multi-walled carbon nanotubes can lead to an increasingly negative surface charge [38]. It has been shown that there is a linear correlation between the total oxygen concentration, surface charge, and critical coagulation coefficient (CCC) of MWCNTs [41]. ...
... Therefore, in biological media containing salts, there can be variable levels of carbon nanotube aggregation, based on the CNT properties. Further, aggregation, and subsequently point of zero charge (PZC), have been linked to embryonic mortality [38]. Yet, most aquatic toxicity studies of nanomaterials do not robustly consider aggregation, and an inaccurate stability assumption can impact conclusions regarding nanomaterial safety [42]. ...
Increasing use of carbon nanotubes (CNTs) in consumer and industrials goods increases their potential release, and subsequent risks to environmental and human health. Therefore, it is becoming ever more important that CNTs are designed to reduce or eliminate hazards and that hazard assessment methodologies are robust. Here, oxygen-functionalized multi-walled CNTs (O-MWCNTs), modified under varying redox conditions, were assessed for toxic potential using the zebrafish (Danio rerio) embryo model. Multiple physicochemical properties (e.g., MWCNT aggregate size, morphology, and rate; surface charge and oxygen concentration; length; and reactive oxygen species (ROS) generation) were characterized and related to zebrafish embryo mortality through the use of multivariate statistical methods. Of these properties, surface charge and aggregate morphology emerged as the greatest predictors of embryo mortality. Interestingly, ROS generation was not significantly correlated to observed mortality, contrary to prior predictions by nanotoxicology researchers. This suggests that the mechanism of MWCNT-induced mortality of embryonic zebrafish is physical, driven by electrostatic and shape effects, both of which are related to nanomaterial aggregation. This raises the importance of rigorously considering aggregation during aqueous-based nanotoxicology assays as nanomaterial aggregation can affect perceived nanomaterial toxicity. As such, future nanotoxicity studies relying on aqueous media must sufficiently consider nanomaterial aggregation.
... Carbon nanotubes from the stock solutions were diluted with double distilled water until the concentrations of 0.1 and 1 ppm working solution were reached. Although these concentrations are higher than the predicted environmental concentration in water (1 × 10 − 9 to 5 × 10 − 7 ppm) [28,29], these are relatively lower than the concentrations used in earlier studies of CNTs in various animal and other models, such as mice (25-10,000 ppm) [40][41][42], green algae (1.8-40 ppm) [30], Oryzias latipes (100 ppm) [27], and adult (2 ppm) [43] and larval zebrafish (0.08-22,050 ppm) [24][25][26]44,45]. In addition, low concentrations of CNTs were chosen considering their higher sensitivity and informativeness than other toxicological and pharmacological assessments. ...
... behavior as the first locomotor activity of zebrafish embryos was evaluated [44,45,48]. Here, the tail-coiling behaviors of each group were monitored after 18 h of exposure to MWCNTs. ...
In recent years, carbon nanotubes (CNTs) have become one of the most promising materials for the technology industry. However, due to the extensive usage of these materials, they may be released into the environment, and cause toxicities to the organism. Here, their acute toxicities in zebrafish embryos and larvae were evaluated by using various assessments that may provide us with a novel perspective on their effects on aquatic animals. Before conducting the toxicity assessments, the CNTs were characterized as multiwall carbon nanotubes (MWCNTs) functionalized with hydroxyl and carboxyl groups, which improved their solubility and dispersibility. Based on the results, abnormalities in zebrafish behaviors were observed in the exposed groups, indicated by a reduction in tail coiling frequency and alterations in the locomotion as the response toward photo and vibration stimuli that might be due to the disruption in the neuromodulatory system and the formation of reactive oxygen species (ROS) by MWCNTs. Next, based on the respiratory rate assay, exposed larvae consumed more oxygen, which may be due to the injuries in the larval gill by the MWCNTs. Finally, even though no irregularity was observed in the exposed larval cardiac rhythm, abnormalities were shown in their cardiac physiology and blood flow with significant downregulation in several cardiac development-related gene expressions. To sum up, although the following studies are necessary to understand the exact mechanism of their toxicity, the current study demonstrated the environmental implications of MWCNTs in particularly low concentrations and short-term exposure, especially to aquatic organisms.
... In most cases, negatively charged particles tend to be safer to organisms due to electrostatic repulsion mechanisms 196,197 Mice were able to tolerate a higher dose of negatively-charged, hydroxylated nano-silica 196 In select cases, positively charged particles can be safer 117,198 MWCNT safety toward embryonic zebrafish increased with increased surface charge 198 Shape ...
... In most cases, negatively charged particles tend to be safer to organisms due to electrostatic repulsion mechanisms 196,197 Mice were able to tolerate a higher dose of negatively-charged, hydroxylated nano-silica 196 In select cases, positively charged particles can be safer 117,198 MWCNT safety toward embryonic zebrafish increased with increased surface charge 198 Shape ...
Currently, over a billion people around the world lack access to clean drinking water, industrial wastewater treatment and reuse is limited, and conventional water treatment systems cannot adequately treat all contaminants of concern. Nanotechnology-enabled water treatment (NWT) has begun to emerge as a viable option to address many of the problems facing the water treatment status quo, either through cost reducing performance enhancements or filling unmet niches. Advancements in fundamental nanoscience allow unprecedented use of catalysis and energy from across the broad electromagnetic spectrum, as well as unique physicochemical properties, to purify drinking water, treat industrial wastewater, and access unconventional water supplies. However, before fully adopting NWT, it is imperative that the devices are both safe and sustainable, enhancing acceptance from consumers, government, non-government organizations, and industry. We suggest that we are in a unique window of time to “do nano right” by making key sustainability considerations very early in nano-water technology development. To this end, we have developed a framework based on three guiding research questions aimed at understanding the breadth of sustainability considerations for NWT at each of the four major life cycle stages – extraction, production, use, and end-of-life. In following this framework, researchers and product developers can design nano-enabled water treatment devices that perform well and are both safe and sustainable. By presenting the current state of sustainable NWT and specifying gaps in the literature, the present review aims to further develop NWT to be the best alternative to conventional water treatment across a variety of sectors.
... Burello & Worth, 2015;Costa, 2016;Fadeel, 2013;Fadeel et al., 2011;Meng et al., 2009;Geraci et al., 2015;ICON, 2010;Lynch et al., 2014;Morose, 2010;Nel et al., 2013;Riediker, 2011;Som et al., 2013, Tinkle, 2010Truong et al., 2012). Recent empirical examples of applying SbD approaches to nanomaterial design include studies on ZnO particles (Le et al., 2016), CuO particles (Naatz et al., 2017), carbon nanotubes (Gilbertson et al., 2016), Au nanoboxes (Movia et al., 2014), CeO 2 particles (Forest et al., 2017) and SiO 2 particles (Lehman et al., 2016). As seen in Table 1, most European nanosafety projects incorporateor see themselves as part of -SbD approaches to varying degrees. ...
... Similarly, Yan et al. (2011) proposed five properties for carbon nanomaterial design to reduce toxicity, such as adding hydrophilic surface modifications. Other examples include metal doping strategies (George et al., 2010;Naatz et al., 2017;Wake et al., 2004), modifying particle surface charge (Fr€ ohlich, 2012;Gilbertson et al., 2016;Harper et al., 2011) as well as shape considerations (e.g. Forest et al., 2017). ...
“Safety by design” (SbD) is an intuitively appealing concept that is on the rise within nanotoxicology and nanosafety research, as well as within nanotechnology research policy. It leans on principles established within drug discovery and development (DDD) and seeks to address safety early, as well as throughout product development. However, it remains unclear what the concept of SbD exactly entails for engineered nanomaterials (ENMs) or how it is envisioned to be implemented. Here, we review the concept as it is emerging in European research and compare its resemblance with the safety testing and assessment practices in DDD. From this comparison, it is clear that “safety” is not obtained through DDD, and that SbD should be considered a starting point rather than an end, meaning that products will still need to progress through thorough safety evaluations and regulation. We conclude that although risk reduction is clearly desirable, the way SbD is currently communicated tends to treat safety as an inherent material property and that this is fundamentally problematic as it represents a recasting and reduction of societal issues into technical problems. SbD therefore faces a multitude of challenges, from practical implementation to unrealistic stakeholder expectations.
... Because pristine CNTs without chemical functionalization are highly insoluble, most studies with zebrafish embryos have used oxidized water-soluble materials. Nevertheless, even oxidized CNTs tend to aggregate in fish exposure media and may accumulate in the mouth, intestines and gills of fish that lead to adverse effects unrelated to any specific interactions of CNTs with fish at the molecular or cellular level (Firme & Bandaru, 2010; Gilbertson et al., 2015;Jackson et al., 2013). In the present article, we have explored the use of Pluronic Õ F-108 (PF108, also known as poloxamer 338), as a dispersant to solubilize and present CNTs to dechorionated zebrafish embryos. ...
... with pMWNTs are significant because, to our knowledge, this is the first report of toxicity studies where embryos have been presented with well-solubilized pMWNTs at such high concentrations. The results with cMWNTs are consistent with data in the literature that oxidized MWNTs with low levels of carboxylation are also not toxic to zebrafish embryos (Adenuga et al., 2013;Gilbertson et al., 2015). The undialyzed pSWNT suspensions caused significant mortality but only at the highest concentration of 200 mg/mL, whereas there was very little effect in the dialyzed samples. ...
Carbon nanotubes (CNTs) are often suspended in Pluronic® surfactants by sonication, which may confound toxicity studies because sonication of surfactants can create degradation products that are toxic to mammalian cells. Here, we present a toxicity assessment of Pluronic® F-108 with and without suspended CNTs using embryonic zebrafish as an in vivo model. Pluronic® sonolytic degradation products were toxic to zebrafish embryos just as they were to mammalian cells. When the toxic Pluronic® fragments were removed, there was little effect of pristine multi-walled CNTs (pMWNTs), carboxylated MWNTs (cMWNTs) or pristine single-walled carbon nanotubes (pSWNTs) on embryo viability and development, even at high concentrations. A gel electrophoretic method coupled with Raman imaging was developed to measure the bioaccumulation of CNTs by zebrafish embryos, and dose-dependent uptake of CNTs was observed. These data indicate that embryos accumulate pMWNTs, cMWNTs and pSWNTs yet there is very little embryo toxicity.
... Because pristine CNTs without chemical functionalization are highly insoluble, most studies with zebrafish embryos have used oxidized water-soluble materials. Nevertheless, even oxidized CNTs tend to aggregate in fish exposure media and may accumulate in the mouth, intestines and gills of fish that lead to adverse effects unrelated to any specific interactions of CNTs with fish at the molecular or cellular level (Firme & Bandaru, 2010; Gilbertson et al., 2015;Jackson et al., 2013). In the present article, we have explored the use of Pluronic Õ F-108 (PF108, also known as poloxamer 338), as a dispersant to solubilize and present CNTs to dechorionated zebrafish embryos. ...
... with pMWNTs are significant because, to our knowledge, this is the first report of toxicity studies where embryos have been presented with well-solubilized pMWNTs at such high concentrations. The results with cMWNTs are consistent with data in the literature that oxidized MWNTs with low levels of carboxylation are also not toxic to zebrafish embryos (Adenuga et al., 2013;Gilbertson et al., 2015). The undialyzed pSWNT suspensions caused significant mortality but only at the highest concentration of 200 mg/mL, whereas there was very little effect in the dialyzed samples. ...
Carbon nanotubes (CNTs) are often suspended in Pluronic® surfactants by sonication, which may confound toxicity studies because sonication of surfactants can create degradation products that are toxic to mammalian cells. Here, we present a toxicity assessment of Pluronic® F-108 with and without suspended CNTs using embryonic zebrafish as an in vivo model. Pluronic® sonolytic degradation products were toxic to zebrafish embryos just as they were to mammalian cells. When the toxic Pluronic® fragments were removed, there was little effect of pristine multi-walled CNTs (pMWNTs), carboxylated MWNTs (cMWNTs) or pristine single-walled carbon nanotubes (pSWNTs) on embryo viability and development, even at high concentrations. A gel electrophoretic method coupled with Raman imaging was developed to measure the bioaccumulation of CNTs by zebrafish embryos, and dose-dependent uptake of CNTs was observed. These data indicate that embryos accumulate pMWNTs, cMWNTs and pSWNTs yet there is very little embryo toxicity.
... Because pristine CNTs without chemical functionalization are highly insoluble, most studies with zebrafish embryos have used oxidized water-soluble materials. Nevertheless, even oxidized CNTs tend to aggregate in fish exposure media and may accumulate in the mouth, intestines and gills of fish that lead to adverse effects unrelated to any specific interactions of CNTs with fish at the molecular or cellular level (Firme & Bandaru, 2010; Gilbertson et al., 2015;Jackson et al., 2013). In the present article, we have explored the use of Pluronic Õ F-108 (PF108, also known as poloxamer 338), as a dispersant to solubilize and present CNTs to dechorionated zebrafish embryos. ...
... with pMWNTs are significant because, to our knowledge, this is the first report of toxicity studies where embryos have been presented with well-solubilized pMWNTs at such high concentrations. The results with cMWNTs are consistent with data in the literature that oxidized MWNTs with low levels of carboxylation are also not toxic to zebrafish embryos (Adenuga et al., 2013;Gilbertson et al., 2015). The undialyzed pSWNT suspensions caused significant mortality but only at the highest concentration of 200 mg/mL, whereas there was very little effect in the dialyzed samples. ...
Carbon nanotubes (CNTs) are often suspended in Pluronic® surfactants by sonication, which may confound toxicity studies because sonication of surfactants can create degradation products that are toxic to mammalian cells. Here, we present a toxicity assessment of Pluronic® F-108 with and without suspended CNTs using embryonic zebrafish as an in vivo model. Pluronic® sonolytic degradation products were toxic to zebrafish embryos just as they were to mammalian cells. When the toxic Pluronic® fragments were removed, there was little effect of pristine multi-walled CNTs (pMWNTs), carboxylated MWNTs (cMWNTs) or pristine single-walled carbon nanotubes (pSWNTs) on embryo viability and development, even at high concentrations. A gel electrophoretic method coupled with Raman imaging was developed to measure the bioaccumulation of CNTs by zebrafish embryos, and dose-dependent uptake of CNTs was observed. These data indicate that embryos accumulate pMWNTs, cMWNTs and pSWNTs yet there is very little embryo toxicity.
... The results from the study indicated that the toxicity of graphene oxide resulted from the envelopment of zebrafish embryo chorion via interactions of the hydroxyl group and pore canal blockage of chorionic membrane, leading to marked hypoxia and delay in hatching of eggs (Chen, Hu, et al., 2016;. The toxicity analysis of both single and multiwalled CNTs using zebrafish has shown that their toxic mechanism is based on surface charge (Gilbertson et al., 2016) and the medium in which they are suspended (Girardi et al., 2017). Carbon-based quantum dots have been used in fluorescence imaging (Kang et al., 2015) and as bio-probes (Zhang et al., 2016) in zebrafish. ...
In vivo toxicological analyses are crucial in demonstrating the efficacy of drugs in the treatment of diseases. Animal models are commonly used for in vivo toxicological and efficacy analysis of drugs. Nanoparticles-based drug formulations or nanomedicines are characterized with varying degrees of toxicity to target and/or nontarget cells in animal models. Hence, it is necessary to comprehensively evaluate nanomedicines to assess their toxicology and therapeutic indices in specific animal models as part of the drug discovery pipeline. Various animals have been used as live models for in vivo assessment of nanomedicines. This chapter discusses different types of in vivo animal models that are used to evaluate toxicity and efficacy of nanomedicines in diabetes treatment.
... To date, researchers have applied diverse methods for attaining this particular surface characteristic modulation. One research group led by Gilbertson et al. has developed a novel statistical model relating the surface charge of CNTs with zebrafish mortality at their embryonic stage [67]. The zebrafish models are the preferred choice for in vivo evaluations in the vertebrate as they have physiological and molecular conservations with the rest of the vertebrates during their embryonic developmental stage [68]. ...
Current discoveries as well as research findings on various types of carbon nanostructures have inspired research into their utilization in a number of fields. These carbon nanostructures offer uses in pharmacy, medicine and different therapies. One such unique carbon nanostructure includes carbon nanotubes (CNTs), which are one-dimensional allotropes of carbon nanostructure that can have a length-to-diameter ratio greater than 1,000,000. After their discovery, CNTs have drawn extensive research attention due to their excellent material properties. Their physical, chemical and electronic properties are excellent and their composites provide great possibilities for enormous nanometer applications. The current study provides a systematic review based on prior literature review and data gathered from various sources. The various research studies from many research labs and organizations were systematically retrieved, collected, compiled and written. The entire collection and compilation of this review concluded the use of CNT approaches and their efficacy and safety for the treatment of various diseases such as brain tumors or cancer via nanotechnology-based drug delivery, phototherapy, gene therapy, antiviral therapy, antifungal therapy, antibacterial therapy and other biomedical applications. The current review covers diverse applications of CNTs in designing a range of targeted drug delivery systems and application for various therapies. It concludes with a discussion on how CNTs based medicines can expand in the future.
... Multiwalled carbon nanotubes Embryo [130] Single wall carbon nanotubes Embryo [131] Graphene quantum dot Embryo [132] Carbon dots Embryo [133] Pristine graphene Embryo [134] Graphene oxide Larvae [135] Fullerene Embryo and adult [136,137] Polymer nanoparticles ...
Recent developments in nanotechnology has increased the market value of nanoproducts in various industries. This has increased concerns associated with potential toxicity of nanoproducts to humans and the environments. Even though, green and biosynthesized nanoparticles are considered to be less toxic than chemically synthesized nanoparticles, they still possess some level of toxicity. Conventional toxicity assessments via human cells, live animals such as rat, frog or rabbit have several drawbacks including ethical issue and challenges involving the maintenance and development of cell cultures. Zebrafish (Danio rerio) is a transparent vertebrate fish that can reproduce rapidly. Its larvae develop in 5 days up to 3-5 cm long. It also possesses about 69% similar genetic profile, molecular mechanism, cell development and organ physiology as humans. Hence, it has the potential to be utilized as an alternative to humans or live animal models for initial drug screening and toxicity tests. European Union, USFDA and ICH have approved the use of zebrafish for toxicological evaluation of pharmaceutical products including nanomedicines. The article presents for the potential of zebrafish in preclinical evaluation of the toxicity of nanomaterials. It also discusses other potential applications, including medical imaging and environmental toxicity.
... Since functionalized CNTs are typically dispersed better in polar solvents and are less prone to agglomeration/aggregation processes, most commercially available CNTs are produced in the chemicallymodified forms. Recent investigations showed that toxicity of these modified forms of CNTs can be influenced by different factors specially grafted functional groups (carboxyl, amine, etc.) onto the sidewalls of CNTs (Esposito et al. 2015, Gilbertson et al. 2016, Song et al. 2019. ...
Carbon nanotubes (CNTs) have great potential as novel diagnostic or therapeutic tools in biomedicine but, cellular toxicity must be well considered before widespread application of CNTs. Many chemical agents exert their toxicity through apoptotic pathways by induction of caspase biomolecules. In the current study, effects of carboxyl-functionalized single-walled (SW) and multi-walled (MW) CNTs at a single dose of 100 µg ml⁻¹ on the survival of Jurkat cells were examined using MTT assay. Additionally, the impacts of carboxylated CNTs on the gene expression levels of selected caspases were investigated. Jurkat cells were exposed to CNTs (100 µg ml⁻¹ for 72 h) and then expression levels of selected caspase genes (Cas) were evaluated by qRT-PCR analysis. Housekeeping genes, β-actin, and glyceraldehyde 3-phosphate dehydrogenase (GAPDH), were used as normalization controls. The results showed only a mild decrease in the viability of Jurkat cells treated with carboxylated MWCNT. The results of qRT-PCR analysis revealed the elevated level of Cas2 mRNA in the cells treated with carboxylated MWCNT (6.08-fold) and carboxylated SWCNT (1.20-fold). The expression levels of Cas4, Cas6, Cas8, and Cas10 genes were increased not significantly compared to the control untreated cells. Our findings suggested that exposure to carboxyl-functionalized CNTs could be resulted in up-regulation of the Cas2 gene and not initiator Cas8 and Cas10 genes. In addition, it seems that carboxylated MWCNT was more potent than SWCNT in activation of Cas2 gene expression and triggering cell death signal in a manner different from intrinsic or extrinsic apoptosis pathways.
... Surface charge plays a major role in the interactions of NPs with the biological systems (Lee et al. 2013;Bozich et al. 2014;Harper et al. 2011) and research groups have employed various ways to to reduce the NP toxic manifestations by screening or modulating the surface characteristics. One such group, Gilbertson et al. (Gilbertson et al. 2016) have established a statistical model relating surface charge and embroyonic zebrafish mortality for a safer MWCNT design. The zebrafish are a preferred in vivo vertebrate model organism and have molecular and physiological conservation with other vertebrates, particularly during embryonic development (Fako and Furgeson 2009;Rizzo et al. 2013;Usenko et al. 2007). ...
Nanomaterials (NMs) find widespread use in different industries that range from agriculture, food, medicine, pharmaceuticals, and electronics to cosmetics. It is the exceptional properties of these materials at the nanoscale, which make them successful as growth promoters, drug carriers, catalysts, filters and fillers, but a price must be paid via the potential toxity of these materials. The harmful effects of nanoparticles (NPs) to environment, human and animal health needs to be investigated and critically examined, to find appropriate solutions and lower the risks involved in the manufacture and use of these exotic materials.
The vast number and complex interaction of NM/NPs with different biological systems implies that there is no universal toxicity mechanism or assessment method. The various challenges need to be overcome and a number of research studies have been conducted during the past decade on different NMs to explore the possible mechanisms of uptake, concentrations/dosage and toxicity levels. This review article examines critically the recent reports in this field to summarize and present opportunities for safer design using case studies from published literature.
... 19,20 Elsewhere, CNT toxicity is often reported to be reduced after functionalization. [21][22][23][24][25] Apart from functionalization, purification is another chemical treatment commonly applied to the CNT samples. Standard purification methods as well involve strong acid treatments which are necessary to eliminate the metallic impurities. ...
Multi walled carbon nanotubes (MWCNTs) are purified by a gas-phase method allowing selective removal of the metallic impurities (Fe and Al catalyst residues) while the MWCNTs remain untouched. Contrary to works using standard purification methods, our approach allows to separately study toxicity due to metallic impurities and that of MWCNTs. Both raw and purified MWCNTs are thoroughly characterized by several techniques including transmission electron microscopy, Raman spectroscopy, thermogravimetric analysis, X-ray photoelectron spectroscopy and adsorption volumetry. The results show that the purification method is efficient and the MWCNT characteristics are well controlled. We study the oxidative stress cell response induced by the MWCNT sample after purification. Cytotoxicity and genotoxicicity are investigated using in vitro micronucleus and comet assays. Our results show that the metallic impurities of the used MWCNTs are not involved in the toxic potential of these CNTs. Consequently, these used CVD-produced MWCNTs alone are responsible for the observed toxic response. This presented approach, applied to other source of CNTs, could be useful for determining the involvement of their metallic impurities in the observed toxic response.
... Further, the functionalization of NPs uses a vast range of physicochemical techniques of ligand attachment and surface modification to enhance properties for targeted drug delivery, controlled release, and decreased immunogenic response. Reports suggest these NPs can be used for augmentation of and/or alternatives to the present antibiotics (Ngoy et al., 2011;Gilbertson et al., 2016). ...
... NPs with a positive surface charge have generally been reported to be more toxic than those with a negative charge (e.g. Fr€ ohlich 2012; H€ uhn et al. 2013;Gilbertson et al. 2016). However, most of these studies have been performed in vitro or in aquatic species, whereas little information is available from in vivo experiments with mammals. ...
Nanoceria has a broad variety of industrial and pharmacological applications due to its antioxidant activity. Nanoceria can be modified by surface coating with polyelectrolyte brushes. Brushes can increase the surface charge of nanoceria, providing greater aqueous stability while reducing agglomeration. However, surface-coating also behaves as a barrier around nanoceria, affecting its redox equilibrium and, hence, its biological and toxicological properties. In the present study, we examined whether bare nanoceria (CeO2; 80–150 nm) and nanoceria modified by surface polymer brush, using negatively charged polyacrylic acid (CeO2@PAA) and positively charged poly (2-(methacryloyloxy)ethyl-trimethyl-ammonium chloride (CeO2@PMETAC), could induce systemic toxicity. As CeO2 has limited colloidal stability, which might result in vascular occlusion, intraperitoneal injection was used instead of intravenous administration. C57Bl/6 mice were four times injected with three different doses of each nanoceria-based sample (corresponding to 1.8, 5.3 and 16 mg Ce/kg BW/administration) for a total period of 14 days. CeO2@PMETAC induced a significant dose-dependent neutrophilia. Histopathological evaluation showed inflammatory processes in the capsule of liver, kidney, and spleen of animals at all doses of CeO2@PMETAC, and with the highest dose of CeO2@PAA and CeO2. However, none of the nanoceria-based samples tested increased the level of DNA damage or micronuclei in blood cells, even though Ce was detected by inductively coupled plasma mass spectrometry analyses in the bone marrow. Only CeO2@PMETAC induced the presence of megakaryocytes in the spleen. A higher accumulation of Ce in mononuclear phagocyte system organs (liver, spleen and bone marrow) was observed after CeO2@PMETAC treatment compared with CeO2@PAA and CeO2.
... There are only a limited number of studies describing statistical and high throughput screening models to identify the relationship between properties and hazard. Recently a model that correlates the surface charge properties of carbon nanotubes and the mortality of zebra fish embryos has been proposed [205]. This may be a good starting point for the development of guidelines to design safer carbon nanotubes and can be clearly expanded to other carbon materials. ...
... CNTs, GFNs, and engineered nanomaterials in general can enter the body via skin penetration, inhalation, ingestion, or biomedical implantation [17]. Gilbertson et al. asserted that the bactericidal properties of dispersed CNTs can be a benefit or a hazardous liability depending on their intended use [45,119,120]. Immobilization of these colloids onto surfaces would open future possibilities while minimizing their dispersal. Indeed, we note a recent shift in the literature from studying bacterial interactions with dispersed CNTs to the incorporation of these nanomaterials in filters for water purification. ...
Over the past ten years, a next-generation approach to combat bacterial contamination has emerged: one which employs nanostructure geometry to deliver lethal mechanical forces causing bacterial cell death. In this review, we first discuss advances in both colloidal and topographical nanostructures shown to exhibit such "mechano-bactericidal" mechanisms of action. Next, we highlight work from pioneering research groups in this area of antibacterials. Finally, we provide suggestions for unexplored research topics that would benefit the field of mechano-bactericidal nanostructures. Traditionally, antibacterial materials are loaded with antibacterial agents with the expectation that these agents will be released in a timely fashion to reach their intended bacterial metabolic target at a sufficient concentration. Such antibacterial approaches, generally categorized as chemical-based, face design drawbacks as compounds diffuse in all directions, leach into the environment, and require replenishing. In contrast, due to their mechanisms of action, mechano-bactericidal nanostructures can benefit from sustainable opportunities. Namely, mechano-bactericidal efficacy needs not replenishing since they are not consumed metabolically, nor are they designed to release or leach compounds. For this same reason, however, their action is limited to the bacterial cells that have made direct contact with mechano-bactericidal nanostructures. As suspended colloids, mechano-bactericidal nanostructures such as carbon nanotubes and graphene nanosheets can pierce or slice bacterial membranes. Alternatively, surface topography such as mechano-bactericidal nanopillars and nanospikes can inflict critical membrane damage to microorganisms perched upon them, leading to subsequent cell lysis and death. Despite the infancy of this area of research, materials constructed from these nanostructures show remarkable antibacterial potential worthy of further investigation.
... But due to the lower negative potential in nano-Se cs and nano-Se cl , the electrostatic repulsion is reduced which possibly increases the chances of the interaction of nano-Se c with embryos and results in higher toxicity (El Badawy et al., 2011). Recently, Gilbertson et al. (2015) reported that surface charge of multi-walled carbon nanotube has the greatest influence on the zebrafish mortality. Several other studies elucidated that the surface charge plays an important role in the observed toxicity trends of nanomaterials using either Daphnia magna or embryonic zebrafish as the in vivo model organisms, which is hypothesized to be governed primarily by the electrostatic interaction between the material and model organism (Bozich et al., 2014;Lee et al., 2013). ...
Microbial reduction of selenium (Se) oxyanions to elemental Se is a promising technology for bioremediation and treatment of Se wastewaters. But a fraction of biogenic nano-Selenium (nano-Se(b)) formed in bioreactors remains suspended in the treated waters, thus entering the aquatic environment. The present study investigated the toxicity of nano-Se(b) formed by anaerobic granular sludge biofilms on zebrafish embryos in comparison with selenite and chemogenic nano-Se (nano-Se(c)). The nano-Se(b) formed by granular sludge biofilms showed a LC50 value of 1.77 mg/L, which was 3.2-fold less toxic to zebrafish embryos than selenite (LC50 = 0.55 mg/L) and 10-fold less toxic than bovine serum albumin stabilized nano-Se(c) (LC50 = 0.16 mg/L). Smaller (nano-Se(cs); particle diameter range: 25-80 nm) and larger (nano-Se(cl); particle diameter range: 50-250 nm) sized chemically synthesized nano-Se(c) particles showed comparable toxicity on zebrafish embryos. The lower toxicity of nano-Se(b) in comparison to nano-Se(c) was analyzed in terms of the stabilizing organic layer. The results confirmed that the organic layer extracted from the nano-Se(b) consisted of components of the extracellular polymeric substances (EPS) matrix, which govern the physiochemical stability and surface properties like ζ-potential of nano-Se(b). Based on the data, it is contented that the presence of humic acid like substances of EPS on the surface of nano-Se(b) plays a major role in lowering the bioavailability (uptake) and toxicity of nano-Se(b) by decreasing the interactions between nanoparticles and embryos.
... The high variability of nanomaterials in terms of chemical composition, size and shape, surface structure, solubility, aggregation and application modes are also factors most likely contributing to the heterogeneity of plant responses reported in the literature [129,130]. Knowledge of the special structural features of nanomaterials determining the adverse effects on living organisms is a pre-requisite for the so called "safe-by-design" approach for a directed design of nanomaterials without negative environmental side effects [131][132][133]. ...
During the relatively short time since the discovery of fullerenes in 1985, carbon nanotubes in 1991, and graphene in 2004, the unique properties of carbon-based nanomaterials have attracted great interest, which has promoted the development of methods for large-scale industrial production. The continuously increasing commercial use of engineered carbon-based nanomaterials includes technical, medical, environmental and agricultural applications. Regardless of the application field, this is also associated with an increasing trend of intentional or unintended release of carbon nanomaterials into the environment, where the effect on living organisms is still difficult to predict. This review describes the different types of carbon-based nanomaterials, major production techniques and important trends for agricultural and environmental applications. The current status of research regarding the impact of carbon nanomaterials on plant growth and development is summarized, also addressing the currently most relevant knowledge gaps.Graphical abstractThe study reviews recent research activities exploring synthesis of carbon nanomaterials, their potential applications and impacts on plant development
... although some inroads have already been made in the environmental area [56]. The progress continuously being made in this area, together with the development in NM quantitative structure-activity relationships, can support the development of safe products such as through Safe by Design [57]. ...
The European Union-United States Communities of Research were established in 2012 to provide a platform for scientists to develop a "shared repertoire of protocols and methods to overcome nanotechnology environmental health and safety (nanoEHS) research gaps and barriers" (www.us-eu.org/). Based on work within the Ecotoxicology Community of Research (2012-2015) the present Focus article provides an overview of the state of the art of nanomaterials (NMs) in the aquatic environment by addressing different research questions, with a focus on ecotoxicological test systems and the challenges faced when assessing NM hazards (e.g., uptake routes, bioaccumulation, toxicity, test protocols, and model organisms). The authors' recommendation is to place particular importance on studying the ecological effects of aged/weathered NMs, as-manufactured NMs, and NMs released from consumer products in addressing the following overarching research topics: 1) NM characterization and quantification in environmental and biological matrices; 2) NM transformation in the environment and consequences for bioavailability and toxicity; 3) alternative methods to assess exposure; 4) influence of exposure scenarios on bioavailability and toxicity; 5) development of more environmentally realistic bioassays; and 6) uptake, internal distribution, and depuration of NMs. Research addressing these key topics will reduce uncertainty in ecological risk assessment and support the sustainable development of nanotechnology. Environ Toxicol Chem 2016;35:1055-1067. © 2016 SETAC.
... For example, broad references to 'nanomaterials' without sufficient context can convey a relatively homogeneous class of materials. Even considering a 'specific' ENM, such as CNTs, only multiwalled-CNT-7 has been classified as possibly carcinogenic to humans by the IARC (Grosse et al. 2014), and modifications of CNTs to improve safety by manufacturing design are possible (Gilbertson et al. 2015). ...
The global construction sector is experiencing major improvements to building materials used in large quantities through commercial applications of nanotechnology. Nano-enabled construction products hold great promise for energy efficiency and resource conservation, but risk assessments lag as new products emerge. This paper presents results from an inventory, survey, and exposure assessment conducted by the authors and explores these findings in the broader context of evolving research trends and responsible development of nanotechnology. An inventory of 458 reportedly nano-enabled construction products provided insight into product availability, potential exposures, and deficiencies in risk communication that are barriers to adoption of proactive safety measures. Seasoned construction trainers surveyed were largely unaware of the availability of nano-enabled construction products. Exposure assessment demonstrated the effectiveness of ventilation to reduce exposures during mechanical abrasion of photocatalytic tiles containing titanium dioxide (TiO2). Dissociated particles of TiO2 just above the nanoscale (138 nm) were detected in the debris collected during cutting of the tiles, but measurements were below recommended exposure limits for TiO2. Exposure assessments remain scarce, and toxicological understanding primarily pertains to unincorporated nanomaterials; less is known about the occupational risks of nano-enabled construction products across their life cycle. Further research is needed to characterize and quantify exposure to debris released from nanocomposite materials for realistic risk assessment, and to ascertain how nanocomposite matrices, fillers, and degradation forces interact to affect release dynamics. Improving risk communication strategies and implementing safe work practices will cultivate responsible development of nanotechnology in construction, as will multidisciplinary research efforts.
... 34,35 With regard to aquatic ecotoxicity of unicellular organisms and embryonic zebrafish, Gilbertson et al. have made efforts to elucidate relationships between empirical toxicity endpoints (e.g., cell viability, embryonic mortality) and some measurable ENM property (e.g., surface oxygen functional group type) for MWCNTs. [36][37][38] The aim of these efforts was not necessarily to elucidate the chemical mechanisms of toxicity, but to instead discover which, if any, ENM properties were correlated with or could be used to predict toxicity, with the ultimate goal of developing design rules. These SPH relationships might hold for other types of carbon-based ENMs and, if so, could accelerate the pace of discovery and ensure safer designs for novel materials coming to market. ...
The Twelve Principles of Green Chemistry were first published in 1998 and provide a framework that has been adopted not only by chemists, but also by design practitioners and decision-makers (e.g., materials scientists and regulators). The development of the Principles was initially motivated by the need to address decades of unintended environmental pollution and human health impacts from the production and use of hazardous chemicals. Yet, for over a decade now, the Principles have been applied to the synthesis and production of engineered nanomaterials (ENMs) and the products they enable. While the combined efforts of the global scientific community have led to promising advances in the field of nanotechnology, there remain significant research gaps and the opportunity to leverage the potential global economic, societal and environmental benefits of ENMs safely and sustainably. As such, this tutorial review benchmarks the successes to date and identifies critical research gaps to be considered as future opportunities for the community to address. A sustainable material design framework is proposed that emphasizes the importance of establishing structure-property-function (SPF) and structure-property-hazard (SPH) relationships to guide the rational design of ENMs. The goal is to achieve or exceed the functional performance of current materials and the technologies they enable, while minimizing inherent hazard to avoid risk to human health and the environment at all stages of the life cycle.
Super Para- magnetic Iron Oxide Nanoparticles (SPIONs) have been manifested for their broad spectrum of applications ranging from biomedical imaging to the treatment of many diseases. Many experiments are being conducted across the globe to especially investigate their potential in the field of targeted treatment for malignant tissues. However, challenges pertaining to the desired delivery of anticancer drugs in the body remain unresolved or unattended. The bare iron oxide nanoparticles are liable to form agglomerates or get easily oxidized in air that can lead to loss of magnetism and viability. Moreover, in several reactions, these magnetic nanoparticles leach into the solution/ suspension, making it kinetically unstable. The nanoparticles, further readily metabolize in the stomach pH or are phagocytosed by macrophages. In this article, we address these issues by shedding light on the impact of controlling parameters like size, synthesis method and surface engineering. After studying the existing literature, it is noted that currently, these magnetically guided delivery systems are being rigorously tested in areas like pancreatic cancer, colon cancer, and prostate cancer, which will be discussed in this review. The fact that the major issue in the conventional treatment of these cancers is intrinsic and acquired drug resistance. In this context, the potential of SPIONs as efficient nanotherapeutics is presented. The article provides a deeper insight into the research performed on these focused areas in cancer. This review also discusses, in brief, the consolidation of artificial intelligence in cancer nanomedicine assuring better treatment outcome in near future.
An A2BO4-type oxygen-deficient perovskite (La2CuO4-δ, LCO), which owns a better low-temperature reducibility, more abundant oxygen vacancies (OVs) and surface oxygen species than the benchmark CuO oxide, was first applied in peroxymonosulfate (PMS) activation. At 0.7 g/L of LCO and 2 mM of PMS, more than 96% of bisphenol A (BPA) was removed within 60 min over a wide pH range of 3.1 ‒ 9.1. The cycle of surface Cu(II)/Cu(I) redox couple and lattice oxygen (O²⁻)/O2 were responsible for PMS activation. Besides, the OVs with localized electrons may directly activate PMS through single electron transfer pathway to generate surface-bound hydroxyl radical (•OH) and sulfate radical (SO4•−), as well as less singlet oxygen (¹O2) for BPA degradation. The evolution of •OH, SO4•− and ¹O2 were revealed by EPR tests. Briefly, this study provides the mechanistic understanding of A2BO4-type perovskite in activation of PMS for water treatment.
Materials at the nanoscale exhibit specific physicochemical interactions with their environment. Therefore, evaluating their toxic potential is a primary requirement for regulatory purposes and for the safer development of nanomedicines. In this review, to aid the understanding of nano–bio interactions from environmental and health and safety perspectives, the potential, reality, challenges, and future advances that artificial intelligence (AI) and machine learning (ML) present are described. Herein, AI and ML algorithms that assist in the reporting of the minimum information required for biomaterial characterization and aid in the development and establishment of standard operating procedures are focused. ML tools and ab initio simulations adopted to improve the reproducibility of data for robust quantitative comparisons and to facilitate in silico modeling and meta‐analyses leading to a substantial contribution to safe‐by‐design development in nanotoxicology/nanomedicine are mainly focused. In addition, future opportunities and challenges in the application of ML in nanoinformatics, which is particularly well‐suited for the clinical translation of nanotherapeutics, are highlighted. This comprehensive review is believed that it will promote an unprecedented involvement of AI research in improvements in the field of nanotoxicology and nanomedicine.
Carbon nanotubes (CNTs) have unique physical and chemical properties that drive their use in a variety of commercial and industrial applications. CNTs are commonly oxidized prior to their use to enhance dispersion in polar solvents by deliberately grafting oxygen-containing functional groups onto CNT surfaces. In addition, CNT surface oxides can be unintentionally formed or modified after CNTs are released into the environment through exposure to reactive oxygen species and/or ultraviolet irradiation. Consequently, it is important to understand the impact of CNT surface oxidation on the environmental fate, transport, and toxicity of CNTs. In this review, we describe the specific role of oxygen-containing functional groups on the important environmental behaviors of CNTs in aqueous media (e.g., colloidal stability, adsorption, and photochemistry) as well as their biological impact. We place special emphasis on the value of systematically varying and quantifying surface oxides as a route to identifying quantitative structure-property relationships. The role of oxygen-containing functional groups in regulating the efficacy of CNT-enabled water treatment technologies and the influence of surface oxides on other carbon-based nanomaterials are also evaluated and discussed.
Nanomaterials have been attracting attention due to the wide range of applications in nanomedicine. Polypyrrole (PPy), a conductive polymer, has been employed in the biomedical field due to its stimulus-responsive properties, although in vivo studies to assess its potential undesirable effects are limited. This study evaluated the effects of PPy doped with p-toluene sulfonic acid ((p-TSA); PPy/p-TSA) exposure (at 25, 100, 250 and 500 μg/mL) during six consecutive days on mortality, hatching, spontaneous movement, heart rate, morphology and locomotion behavior of zebrafish embryos/larvae. Additionally, PPy/p-TSA envelopment of developing embryo chorions and gene expression of a hypoxia-related marker in this context were also evaluated. No significant mortality was found; however, altered heart rate and early hatching was identified in all exposed groups at 48 hours post-fertilization (hpf). Surprisingly, with the 500 μg/mL dose, hatching initiated as early as 24 hpf. PPy/p-TSA adhered to and enveloped the chorion of embryos in a time- and dose-dependent fashion; morphological changes in body length and ocular distance were found with higher concentrations. PPy/p-TSA-exposed animals showed locomotor behavioral alterations compatible with hypoactivity. A significant increase in the turn angle with a concomitant reduction in meander was also verified at higher concentrations. Taken together, these results emphasize the adverse effects of PPy/p-TSA on zebrafish development and behavior. Some effects of PPy/p-TSA exposure were dose-dependent, and indicate specific adverse effects of PPy/p-TSA on zebrafish development and behavior.
In recent years, the use of commercial nanoparticles in different industry and health fields has increased exponentially. However, the uncontrolled application of nanoparticles might present a potential risk to the environment and health. Toxicity of these nanoparticles is usually evaluated by a fast screening assay in zebrafish (Danio rerio). The use of this vertebrate animal model has grown due to its small size, great adaptability, high fertilization rate and fast external development of transparent embryos. In this review, we describe the toxicity of different micro- and nanoparticles (carbon nanotubes, dendrimers, emulsions, liposomes, metal nanoparticles, and solid lipid nanoparticles) associated to their biophysical properties using this model. The main biophysical properties studied are size, charge and surface potential due to their impact on the environment and health effects. The review also discusses the correlation of the effects of the different nanoparticles on zebrafish. Special focus is made on morphological abnormalities, altered development and abnormal behavior. The last part of the review debates changes that should be made in future directions in order to improve the use of the zebrafish model to assess nanotoxicity.
It is well known that surfactant-suspended carbon nanotube (CNT) samples can be purified by centrifugation to decrease agglomerates and increase individually-dispersed CNTs. However, centrifugation is not always part of protocols to prepare CNT samples used in biomedical applications. Herein, using carboxylated multi-walled CNTs (cMWCNTs) suspended in water without a surfactant, we developed a Boehm titrimetric method for the analysis of centrifuged cMWCNT suspensions and used it to show that the surface acidity of oxidized carbon materials in aqueous cMWCNT suspensions was enriched by ∼40% by a single low-speed centrifugation step. This significant difference in surface acidity between un-centrifuged and centrifuged cMWCNT suspensions has not been previously appreciated and is important because the degree of surface acidity is known to affect the interactions of cMWCNTs with biological systems.
Nanoparticles (NPs) are the basis of a range of emerging technologies used for a variety of industrial, biomedical, and environmental applications. As manufactured NP production increases, so too does the concern about their release into the environment and potentially harmful effects. Creating nanomaterials that have minimal negative environmental impact will heavily influence the sustainability of nanomaterials as a technology. In order to create such NPs, the mechanisms that govern NP toxicity need to be better elucidated. One aspect of NP structure that may influence toxicity is the identity and charge of ligand molecules used to functionalize the NP surface. These surface chemistries have the potential to increase or decrease negative biological impacts, yet their impacts are poorly understood. In this study, the toxicity of three types of functionalized ~4–5 nm gold NPs (AuNPs), polyallylamine hydrochloride (PAH–AuNPs), citrate (Cit–AuNPs) and mercaptopropionic acid (MPA–AuNPs) as well as cetyltrimethylammonium bromide-functionalized gold nanorods (CTAB–AuNRs) were evaluated in the toxicological model species, Daphnia magna. In order to get the most detailed information on NP toxicity in D. magna, both acute and chronic toxicity assays were performed. Acute exposure toxicity assays show that overall the negatively-charged AuNPs tested are orders of magnitude less toxic than the positively-charged AuNPs. However, chronic exposure assays show that both positively and negatively-charged particles impact reproduction but potentially through different mechanisms and dependent upon functional group. In addition, while select ligands used in NP functionalization (such as CTAB) that are toxic on their own can contribute to observed NP toxicity, our acute toxicity assays indicate that minimally toxic ligands (such as PAH) can also cause significant toxicity when conjugated to NPs. This research demonstrates that surface chemistry plays a pivotal role in NP toxicity and that surface chemistry has the potential to affect the sustainability of these materials. Nano impact Understanding the impacts of engineered NP exposure on aquatic organisms is essential to predict the environmental implications of nanotechnology, however issues with nanomaterial synthesis and characterization often plague these studies. In this study the acute and chronic toxicity of well characterized gold nanoparticles functionalized with ligands of differing charges were investigated in Daphnia magna. We found that AuNP toxicity was highly dependent on both NP charge and ligand identity where positively charged nanomaterials were more toxic and certain ligands were only toxic when associated with the nanomaterial. Select negatively charged nanomaterials also impacted reproduction. This experiment illustrates the need for well-characterized nanomaterials to determine the impacts of nanomaterial properties on toxicity to inform the safe and sustainable development of nanomaterials.
Significance
Two of the rigorous disciplines that have emerged over the last 20 y to empower sustainability science are industrial ecology and green chemistry. Robust assessment tools of industrial ecology identify the greatest opportunities to mitigate human health and environmental impacts resulting from human activity. Green chemistry designs and develops chemicals, materials, and processes that, throughout the life cycle, minimize hazard and maximize efficiency. This process often entails synthesizing new molecules while maintaining function and minimizing adverse outcomes, particularly toxicity. There is an urgent need to develop accurate and economical screening tools that predict potential toxicity and inform the design of safer alternatives. A computational approach is presented for the rational design of molecules for reduced acute aquatic toxicity.
Nanoparticles are increasingly used for biomedical purposes. Many different diagnostic and therapeutic applications are envisioned for nanoparticles, but there are often also serious concerns regarding their safety. Given the fact that numerous new nanomaterials are being developed every day, and that not much is known about the long-term toxicological impact of exposure to nanoparticles, there is an urgent need to establish efficient methods for nanotoxicity testing. The zebrafish (Danio rerio) embryo assay has recently emerged as an interesting 'intermediate' method for in vivo nanotoxicity screening, enabling (semi-) high-throughput analyses in a system significantly more complex than cultured cells, but at the same time also less 'invasive' and less expensive than large-scale biocompatibility studies in mice or rats. The zebrafish embryo assay is relatively well-established in the environmental sciences, but it has not yet gained wide notice in the nanomedicine field. Using prototypic polymeric drug carriers, gold-based nanodiagnostics and nanotherapeutics, and iron oxide-based nanodiagnostics, we here show that toxicity testing using zebrafish embryos is easy, efficient and informative, and faithfully reflects, yet significantly extends, cell-based toxicity testing. We therefore expect that the zebrafish embryo assay will become a popular future tool for in vivo nanotoxicity screening.
Carbon nanotubes (CNTs) are currently one of the most important classes of nanomaterials with unique properties sparking off numerous applications in many fields, including electronics, material science and medicine. However, applications of CNTs in medicine and other biological fields are hampered by their insolubility in aqueous media and concerns regarding toxicity. In this study, seven types of CNTs, including two single-walled, one double-walled, and four multi-walled, were evaluated for possible toxicological effects. Soluble CNTs were prepared by treatment with a mixture of acids (D2SO4 and DNO3), washed with Milli-Q water and oven dried. Transmission electron microscopy, thermal gravimetric analysis, and other techniques were used to characterise the prepared CNTs. CNT toxicity was assessed using the embryonic zebrafish. Results showed that none of the CNTs studied caused significant adverse developmental effects. These results support the potential safe use of CNTs as components of indwelling medical devices and drug delivery tools.
The routine rational design of commercial chemicals with minimal toxicological hazard to humans and the environment is a key goal of green chemistry. The development of such a design strategy requires an understanding of the interrelationships between physical–chemical properties, structure, mechanisms and modes of action. This study develops property-based guidelines for the design of chemicals with reduced chronic aquatic toxicity to multiple standardized species and endpoints by exploring properties associated with bioavailability, narcotic toxicity and reactive modes of action, such as electrophilic interactions. Two simple properties emerge as key parameters that distinguish chemicals in the Low EPA level of concern to three aquatic species from those in the High level of concern – octanol–water partition coefficient, (log Po–w) and ΔE (LUMO–HOMO energy gap). Physicochemical properties were predicted using Schrodinger's QikProp, while frontier orbital energies were determined based on AM1 and DFT calculations using Gaussian03. Experimental toxicity data used consisted of chronic toxicity thresholds (NOEC) for Daphnia magna reproduction (317 compounds, 504 h-assay) and Oryzias latipes (Japanese medaka, 122 compounds in 336, 504 and 672 h assays) survival, and Pseudokirchneriella subcapitata, a green algae model (392 compounds). Results indicate that 92% of compounds of Low chronic concern have log Po–w values < 2 and ΔE > 9 eV. Chronically safe compounds to P. subcapitata meet similar criteria – 80% have log Po–w values < 3 and ΔE greater than 9 eV. Our work proposes design guidelines that can be used to significantly increase the probability that a chemical will have low chronic toxicity, based on the endpoints evaluated, to the three diverse aquatic species studied, and potentially to other aquatic species.
Worldwide commercial interest in carbon nanotubes (CNTs) is reflected in a production capacity that presently exceeds several
thousand tons per year. Currently, bulk CNT powders are incorporated in diverse commercial products ranging from rechargeable
batteries, automotive parts, and sporting goods to boat hulls and water filters. Advances in CNT synthesis, purification,
and chemical modification are enabling integration of CNTs in thin-film electronics and large-area coatings. Although not
yet providing compelling mechanical strength or electrical or thermal conductivities for many applications, CNT yarns and
sheets already have promising performance for applications including supercapacitors, actuators, and lightweight electromagnetic
shields.
Many potential applications in nanotechnology envisage the use of better-dispersed and functionalized preparations of carbon nanotubes. Single-walled carbon nanotubes (SWCNTs) were treated with 1:1 mixtures of concentrated nitric and sulfuric acids for 3 min in a microwave oven under 20 psi pressure followed by extensive dialysis to remove the acids. This treatment resulted in acid functionalized SWCNTs (AF-SWCNTs) that had high negative charge (Zeta potential −40 to −60 mV) and were well dispersed (98% of the particles <150 nm) in aqueous suspensions. In vitro and in vivo toxic effects of SWCNTs and AF-SWCNTs were compared. AF-SWCNTs exerted a strong cytotoxic effect on LA4 mouse lung epithelial cells in culture that could be blocked by prior treatment of the nanotubes with poly L-lysine which neutralized the electric charge and promoted re-agglomeration. AF-SWCNT, but not the unmodified SWCNT preparations, strongly inhibited cell cycling of LA4 cells. Both SWCNTs and AF-SWCNTS were however equally effective in inducing apoptotic responses in LA4 cells as examined using an Annexin V binding assay. Oro-pharyngeal aspiration of AF-SWCNT preparation induced a strong acute inflammatory response in the lungs of CD1 mice, compared to control SWCNTs which caused only a marginal effect. Taken together the results indicate that unlike pristine SWCNTs, acid-functionalized SWCNT preparations exert strong toxic effects in vitro and in vivo and these effects can be reversed by neutralizing their surface charge.
There is currently a large difference of opinion in nanotoxicology studies of nanomaterials. There is concern about why some studies have indicated that there is strong toxicity, while others have not. In this study, the length of carbon nanotubes greatly affected their toxicity in zebrafish embryos. Multiwalled carbon nanotubes (MWCNTs) were sonicated in a nitric acid solution for 24 hours and 48 hours. The modified MWCNTs were tested in early developing zebrafish embryo. MWCNTs prepared with the longer sonication time resulted in severe developmental toxicity; however, the shorter sonication time did not induce any obvious toxicity in the tested developing zebrafish embryos. The cellular and molecular changes of the affected zebrafish embryos were studied and the observed phenotypes scored. This study suggests that length plays an important role in the in vivo toxicity of functionalized CNTs. This study will help in furthering the understanding on current differences in toxicity studies of nanomaterials.
Production processes for carbon nanotubes often produce mixtures of solid morphologies that are mechanically entangled or that self-associate into aggregates. Entangled or aggregated nanoparticles often need to be dispersed into fluid suspensions in order to develop materials that have unique mechanical characteristics or transport properties. This paper reviews the effects of milling, ultrasonication, high shear flow, elongational flow, functionalization, and surfactant and dispersant systems on morphology of carbon nanotubes and their interactions in the fluid phase. Multiwalled carbon nanotubes (MWNTs) have been used as an example model system for experimental work because they have been available in engineering-scale quantities and can be dispersed reproducibly in a variety of solvents and polymers. Their size scales, $30–50 nm in average diameter and $5–50 microns in length, permit MWNT dispersions to be investigated using transmission electron microscopy, scanning electron microscopy, and in some cases, light microscopy.
Carbon nanotubes are unique tubular structures of nanometer diameter and large length/diameter ratio. The nanotubes may consist of one up to tens and hundreds of concentric shells of carbons with adjacent shells separation of ∼0.34 nm. The carbon network of the shells is closely related to the honeycomb arrangement of the carbon atoms in the graphite sheets. The amazing mechanical and electronic properties of the nanotubes stem in their quasi-one-dimensional (1D) structure and the graphite-like arrangement of the carbon atoms in the shells. Thus, the nanotubes have high Young’s modulus and tensile strength, which makes them preferable for composite materials with improved mechanical properties. The nanotubes can be metallic or semiconducting depending on their structural parameters. This opens the ways for application of the nanotubes as central elements in electronic devices including field-effect transistors (FET), single-electron transistors and rectifying diodes. Possibilities for using of the nanotubes as high-capacity hydrogen storage media were also considered. This report is intended to summarize some of the major achievements in the field of the carbon nanotube research both experimental and theoretical in connection with the possible industrial applications of the nanotubes.
The potential of the developing zebrafish model for toxicology and drug discovery is limited by inefficient approaches to manipulating and chemically exposing zebrafish embryos-namely, manual placement of embryos into 96- or 384-well plates and exposure of embryos while still in the chorion, a barrier of poorly characterized permeability enclosing the developing embryo. We report the automated dechorionation of 1600 embryos at once at 4 h postfertilization (hpf) and placement of the dechorionated embryos into 96-well plates for exposure by 6 hpf. The process removed ≥95% of the embryos from their chorions with 2% embryo mortality by 24 hpf, and 2% of the embryos malformed at 120 hpf. The robotic embryo placement allocated 6-hpf embryos to 94.7% ± 4.2% of the wells in multiple 96-well trials. The rate of embryo mortality was 2.8% (43 of 1536) from robotic handling, the rate of missed wells was 1.2% (18 of 1536), and the frequency of multipicks was <0.1%. Embryo malformations observed at 24 hpf occurred nearly twice as frequently from robotic handling (16 of 864; 1.9%) as from manual pipetting (9 of 864; 1%). There was no statistical difference between the success of performing the embryo placement robotically or manually.
We highlight the heterogeneity and electro-catalysis of multi-walled carbon nanotubes which is shown to be dependant on batch to batch variation via the use of cyclic voltammetry, X-ray photoelectron spectroscopy and transmission electron microscopy. Batch to batch variation is often an overlooked parameter which may limit their use in electrochemistry, and in particular, in the development and realisation of commercial electroanalytical sensors and therefore needs to be considered.
Abstract Embryonic zebrafish were used to assess the impact of solution ion concentrations on agglomeration and resulting in vivo biological responses of gold nanoparticles (AuNPs). The minimum ion concentration necessary to support embryonic development was determined. Surprisingly, zebrafish exhibit no adverse outcomes when raised in nearly ion-free media. During a rapid throughput screening of AuNPs, 1.2-nm 3-mercaptopropionic acid-functionalized AuNPs (1.2-nm 3-MPA-AuNPs) rapidly agglomerate in exposure solutions. When embryos were exposed to 1.2-nm 3-MPA-AuNPs dispersed in low ionic media, both morbidity and mortality were induced, but when suspended in high ionic media, there was little to no biological response. We demonstrated that the media ionic strength greatly affects agglomeration rates and biological responses. Most importantly, the insensitivity of the zebrafish embryo to external ions indicates that it is possible, and necessary, to adjust the exposure media conditions to optimize NP dispersion prior to assessment.
The embryonic zebrafish model offers the power of whole-animal investigations (e.g., intact organism, functional homeostatic feedback mechanisms, and intercellular signaling) with the convenience of cell culture (e.g., cost- and time-efficient, minimal infrastructure, small quantities of nanomaterial solutions required). The model system overcomes many of the current limitations in rapid to high-throughput screening of drugs/compounds and casts a broad net to evaluate integrated system effects rapidly. Additionally, it is an ideal platform to follow up with targeted studies aimed at the mechanisms of toxic action. Exposures are carried out in 96-well plates so minimal solution volumes are required for the assessments. Numerous morphological, developmental, and behavioral endpoints can be evaluated noninvasively due to the transparent nature of the embryos.
The amino multi-walled carbon nanotubes (AMWNT) are fabricated taking carboxylic MWNTs as raw materials by acylchlorides, amidation and Hoffman degradation. The product reacts with adipic acid-hexamethylene diamine salts by in situ polymerization. Transmission Electronic Microscopy (TEM), Fourier Transform Infrared Spectroscope (FTIR), Raman Spectroscope, Thermogravimetric Analysis (TG) and X-ray Photoelectron Spectroscopy (XPS) are used to characterize the structure and properties of AMWNT and nanocomposite. The results show that: Amino group is linked to the surface of MWNTs and approximately 91 of every 1 000 carbon atoms on the surface of MWNTs are transformed into amino groups; however, the thermal stability of AMWNT is inferior to that of MWNTs; poly (adipic acid-hexamethylene diamine) functionalized AMWNT nanocomposites are fabricated successfully by in situ polymerization of AMWNT and adipic acid-hexamethylene diamine salts and it illustrates that the amino groups on MWNT are polycondensation reactive.
A new global test statistic for models with continuous covariates and binary response is introduced. The test statistic is based on nonparametric kernel methods. Explicit expressions are given for the mean and variance of the test statistic. Asymptotic properties are considered and approximate corrections due to parameter estimation are presented. Properties of the test statistic are studied by simulation. The goodness-of-fit method is illustrated on data from a Dutch follow-up study on preterm infants. Recommendations for practitioners are given.
Because of their unique physical, chemical, electrical, and mechanical properties, carbon nanotubes (CNTs) have attracted a great deal of research interest and have many potential applications. As large-scale production and application of CNTs increases, the general population is more likely to be exposed to CNTs either directly or indirectly, which has prompted considerable attention about human health and safety issues related to CNTs. Although considerable experimental data related to CNT toxicity at the molecular, cellular, and whole animal levels have been published, the results are often conflicting. Therefore, a systematic understanding of CNT toxicity is needed but has not yet been developed.
Basic toxicological information is lacking for the majority of industrial chemicals. In addition to increasing empirical toxicity data through additional testing, prospective computational approaches that drug development aim to serve as a rational basis for the design of chemicals with reduced toxicity. Recent work by our research team has resulted in the derivation of a “rule of two,” wherein chemicals with logP < 2 and ▵E > 9eV are predicted to be 4–5 times less likely to elicit acute or chronic toxicity to model aquatic organisms. The present study examines potential reduction of aquatic toxicity hazards from industrial chemicals if these two molecular design guidelines were employed. Probabilistic hazard assessment approaches were used to model the likelihood of encountering industrial chemicals exceeding toxicological categories of concern both with and without the “rule of two”. Modeling predicted that utilization of these molecular design guidelines for logP and ▵E would appreciably decrease the number of chemicals that would be designated to be of ‘high’ and ‘very high’ concern for acute and chronic toxicity to standard model aquatic organisms and endpoints as defined by the US Environmental Protection Agency. For example, 14.5% of chemicals were categorized as having high and very high acute toxicity to the fathead minnow model, while only 3.3% of chemicals conforming to the design guidelines were predicted to be in these categories. Considerations of specific chemical classes (e.g., aldehydes), chemical attributes (e.g., ionization) and adverse outcome pathways in representative species (e.g., receptor mediated responses) could be used to derive future property guidelines for broader classes of contaminants. Environ Toxicol Chem © 2014 SETAC
Multi-walled carbon nanotubes (MWNTs) are utilized in a number of sectors as a result of their favorable electronic properties. In addition, MWNT antimicrobial properties can be exploited or considered a potential liability depending on their intended application and handling. The ability to tailor electrochemical and antimicrobial properties using economical and conventional treatment processes introduces the potential to significantly enhance product performance. Oxygen functional groups are known to influence several MWNT properties, including redox activity. Here, MWNTs were functionalized with oxygen groups using standard acid treatments followed by selective reduction via annealing. Chemical derivatization coupled to X-ray photoelectron spectroscopy was utilized to quantify specific surface oxygen group concentration after variable treatment conditions, which were then correlated to observed trends in electrochemical and antimicrobial activities. These activities were evaluated as the potential for MWNTs to participate in the oxygen reduction reaction and to have the ability to promote the oxidation of glutathione. The compiled results strongly suggest that the reduction of surface carboxyl groups and the redox activity of carbonyl groups promote enhanced MWNT reactivity and elucidate the opportunity to design functional MWNTs for enhanced performance in their intended electrochemical or antimicrobial application.
Extended abstract of a paper presented at Microscopy and Microanalysis 2005 in Honolulu, Hawaii, USA, July 31--August 4, 2005.
A method is proposed to estimate the point of zero charge (pzc) of pure compounds which can be described accurately by the surface ionization model of amphoteric oxides. It is demonstrated that under the limiting conditions of “infinite” mass/volume ratio, the pH of the system will approach . Experimental values of the pH of the oxides of titanium, aluminum, a silicon suspended in a closed aqueous system exhibited the existence of a constant pH at high mass fractions. This limiting pH is found to be a reasonable estimate for the point of zero charge of each oxide.
The potential applications as well as the environmental and human health implications of carbon nanomaterials (CNMs) are well represented in the literature. There has been a recent focus on how specific physicochemical properties influence carbon nanotube (CNT) function as well as cytotoxicity. The ultimate goal is a better understanding of the causal relationship between fundamental physiochemical properties and cytotoxic mechanism in order to both advance functional design and to minimize unintended consequences of CNTs. This study provides characterization data on a series of multi-walled carbon nanotubes (MWNTs) that underwent acid treatment followed by annealing at increasing temperatures, ranging from 400 - 900 °C. These results show that MWNTs can be imparted with the same toxicity as single-walled carbon nanotubes (SWNTs) by acid treatment and annealing. Further, we were able to correlate this toxicity to the chemical reactivity of the MWNT suggesting that it is a chemical rather than physical hazard. This informs the design of MWNT to be less hazardous or enables their implementation in antimicrobial applications. Given the reduced cost and ready dispersivity of MWNT as compared to SWNT, there is a significant opportunity to pursue the use of MWNT in novel applications previously thought reserved for SWNT.
Nanomaterials possess unusually high surface area-to-volume ratios, and surface-determined physicochemical properties. It is essential to understand their surface-dependent toxicity in order to rationally design biocompatible nanomaterials for a wide variety of applications. In this study, we have functionalized the surfaces of silver nanoparticles (Ag NPs, 11.7 ± 2.7 nm in diameters) with three biocompatible peptides (CALNNK, CALNNS, CALNNE) to prepare positively (Ag-CALNNK NPs+ζ), negatively (Ag-CALNNS NPs-2ζ), and more negatively charged NPs (Ag-CALNNE NPs-4ζ), respectively. Each peptide differs in a single amino acid at its C-terminus, which minimizes the effects of peptide sequences and serves as a model molecule to create positive, neutral and negative charges on the surface of the NPs at pH 4-10. We have studied their charge-dependent transport into early-developing (cleavage-stage) zebrafish embryos and their effects on embryonic development using dark-field optical microscopy and spectroscopy (DFOMS). We found that all three Ag-peptide NPs passively diffused into the embryos via their chorionic pore canals, and stayed inside the embryos throughout their entire development (120 h), showing charge-independent diffusion modes and charge-dependent diffusion coefficients. Notably, the NPs create charge-dependent toxic effects on embryonic development, showing that the Ag-CALNNK NPs+ζ (positively charged) are the most biocompatible while the Ag-CALNNE NPs-4ζ (more negatively charged) are the most toxic. By comparing with our previous studies of the same sized citrated Ag and Au NPs, the Ag-peptide NPs are much more biocompatible than the citrated Ag NPs, and nearly as biocompatible as the Au NPs, showing the dependence of nanotoxicity upon the surface charges, surface functional groups and chemical compositions of the NPs. This study also demonstrates powerful applications of single NP plasmonic spectroscopy for quantitative analysis of single NPs in vivo and in tissues, and reveals the possibility of rational design of biocompatible NPs.
Activated carbons have a disordered graphitic structure, which has been described as compared to to wrinkled paper sheets. The presence of heteroatoms (such as O, N, H, S, etc) bound to the edges of the graphene layers originates a variety of surface functional groups. Oxygenated functionalities have been most extensively studied, since they are formed spontaneously by exposure of the carbon material to the atmosphere; however, nitrogen, sulfur and phosphorous groups can also be found. The nature and concentration of surface functional groups may be modified by suitable thermal or chemical treatments. Treatments in the gas or liquid phase can be used to increase the concentration of surface groups, while heating under inert atmosphere may be used to selectively remove some of those functionalities. A variety of experimental techniques has been used to characterise functional groups, such as chemical titration methods, temperature-programmed desorption, X-ray photoelectron spectroscopy and infra-red spectroscopy methods. The results obtained by temperature-programmed desorption agree quantitatively with the elemental and proximate analyses of the oxidized materials, and qualitatively with the observations by infra-red spectroscopy. Some applications of functionalised activated carbons in adsorption and catalysis for several reactions are mentioned.
To assure a responsible and sustainable growth of nanotechnology, the environmental health and safety (EHS) aspect of engineered nanomaterials and nano-related products needs to be addressed at a rate commensurate with the expansion of nanotechnology. Zebrafish has been demonstrated as a correlative in vivo vertebrate model for such task, and the current advances of using zebrafish for nano EHS studies are summarized here. In addition to morphological and histopathological observations, the accessibility of gene manipulation would greatly empower such a model for detailed mechanistic studies of any nanoparticles of interest. The potential for establishing high-throughput screening platforms to facilitate the nano EHS studies is highlighted, and a discussion is presented on how toxicogenomics approaches represent a future direction to guide the identification of toxicity pathways.
This paper describes the issues relating to the measurement of nanoparticle size, shape and dispersion when evaluating the toxicity of nanoparticles. Complete characterization of these materials includes much more than size, size distribution and shape; nonetheless, these attributes are usually the essential foundation. The measurement of particle size, particularly at scales of 100 nm or less, can be challenging under the best of conditions. Measurements that are routine in the laboratory setting become even more difficult when made under the physiological conditions relevant to toxicity studies, where the environment of the particles can be quite complex. Passive and active cellular responses, as well as the presence of a variety of nano-scale biological structures, often complicate the collection and interpretation of size and shape data. In this paper, we highlight several of the common issues faced when characterizing nanoparticles for toxicity testing and suggest general protocols to address these problems.
This review explores the state-of-the-art applications of various kinds
of carbon nanotubes. We will address the uniqueness of nanotubes that
makes them better than their competitors for specific applications. We will
discuss several examples of the already existing commercial uses of nanotubes
and then point out feasible nanotube applications for the near term (within
ten years) and the long term (beyond ten years). In our discussions of the
applications, we will distinguish between the various kinds of nanotubes
in play today, ranging from multiwall nanotubes having different degrees
of perfection to the near-perfect molecular single-wall nanotubes. The last
decade of research in this field points to several possible applications for
these materials; electronic devices and interconnects, field emission devices,
electrochemical devices, such as supercapacitors and batteries, nanoscale sensors,
electromechanical actuators, separation membranes, filled polymer composites,
and drug-delivery systems are some of the possible applications that have
been demonstrated in the laboratories. We further discuss the status of this
field and point out the value-added applications that exist today versus the
revolutionary applications that will ensue in the distant future. The opportunities,
challenges and the major bottlenecks, including large-scale manufacturing for
nanotube material, will be identified as we define the applications space for
nanotubes. We will also consider some of the recent concerns regarding health,
environment as well as handling and safety protocols for carbon nanotubes.
The production of engineered nanomaterials (ENMs) is a sci-entific breakthrough in material design and the development of new consumer products. While the successful implementation of nanotechnology is important for the growth of the global economy, we also need to consider the possible environmental health and safety (EHS) impact as a result of the novel physicochemical properties that could generate hazardous biological outcomes. In order to assess ENM hazard, reliable and reproducible screening approaches are needed to test the basic materials as well as nanoenabled products. A platform is required to investigate the potentially endless number of biophysicochemical interactions at the nano/bio interface, in response to which we have developed a predictive toxicological approach. We define a predictive toxicological approach as the use of mechanisms-based high-throughput screening in vitro to make predictions about the physicochemical properties of ENMs that may lead to the generation of pathology or disease outcomes in vivo. The in vivo results are used to validate and improve the in vitro high-throughput screening (HTS) and to establish structure-activity relationships (SARs) that allow hazard ranking and modeling by an appropriate combination of in vitro and in vivo testing. This notion is in agreement with the landmark 2007 report from the US National Academy of Sciences, "Toxicity Testing in the 21st Century: A Vision and a Strategy" ( http://www.nap.edu/catalog.php?record_id=11970 ), which advocates increased efficiency of toxicity testing by transitioning from qualitative, descriptive animal testing to quantitative, mechanistic, and pathway-based toxicity testing in human cells or cell lines using high-throughput approaches. Accordingly, we have implemented HTS approaches to screen compositional and combinatorial ENM libraries to develop hazard ranking and structure-activity relationships that can be used for predicting in vivo injury outcomes. This predictive approach allows the bulk of the screening analysis and high-volume data generation to be carried out in vitro, following which limited, but critical, validation studies are carried out in animals or whole organisms. Risk reduction in the exposed human or environmental populations can then focus on limiting or avoiding exposures that trigger these toxicological responses as well as implementing safer design of potentially hazardous ENMs. In this Account, we review the tools required for establishing predictive toxicology paradigms to assess inhalation and environmental toxicological scenarios through the use of compositional and combinatorial ENM libraries, mechanism-based HTS assays, hazard ranking, and development of nano-SARs. We will discuss the major injury paradigms that have emerged based on specific ENM properties, as well as describing the safer design of ZnO nanoparticles based on characterization of dissolution chemistry as a major predictor of toxicity.
The thermal stability and the reducibility of oxygen-containing functional groups on the surface of nitric acid-treated multiwalled carbon nanotubes (CNTs) have been studied using temperature-programmed desorption and reduction (TPD and TPR) and high-resolution X-ray photoelectron spectroscopy (XPS). The thermal treatments up to 720 degrees C were carried out in the XPS setup, either under ultrahigh vacuum (UHV) or in diluted hydrogen. Deconvoluted XP spectra were used for the quantitative determination of the amount of the different functional groups on the CNT surfaces as a function of the pretreatment. The number of the oxygen atoms per unit surface area was obtained from the oxygen to carbon (O/C) ratio derived from the corresponding peak areas in the XP spectra. The results obtained by XPS agree quantitatively with the observations by TPD and TPR. The acid treatment not only introduced carboxyl, carbonyl, and phenol groups on the surface but also generated ether-type oxygen groups between the graphitic layers as indicated by the oxygen balance. Generally, the presence of hydrogen decreased the thermal stability of the oxygen-containing functional groups. Both XPS and TPR provided evidence for the reduction of carboxylic groups to phenolic groups at 300 degrees C in hydrogen. Heating in hydrogen was found to be more effective in removing the oxygen-containing functional groups compared to heating in UHV but did not allow either to remove all oxygen species even at 720 degrees C.
The addition of surface functional groups to single-walled carbon nanotubes (SWNTs) is realized as an opportunity to achieve enhanced functionality in the intended application. At the same time, several functionalized SWNTs (fSWNTs), compared to SWNTs, have been shown to exhibit decreased cytotoxicity. Therefore, this unique class of emerging nanomaterials offers the potential enhancement of SWNT applications and potentially simultaneous reduction of their negative human health and environmental impacts depending on the specific functionalization. Here, the percent cell viability loss of Escherichia coli K12 resulting from the interaction with nine fSWNTs, n-propylamine, phenylhydrazine, hydroxyl, phenydicarboxy, phenyl, sulfonic acid, n-butyl, diphenylcyclopropyl, and hydrazine SWNT, is presented. The functional groups range in molecular size, chemical composition, and physicochemical properties. While physiochemical characteristics of the fSWNTs did not correlate, either singularly or in combination, with the observed trend in cell viability, results from combined light scattering techniques (both dynamic and static) elucidate that the percent loss of cell viability can be correlated to fSWNT aggregate size distribution, or dispersity, as well as morphology. Specifically, when the aggregate size polydispersity, quantified as the width of the distribution curve, and the aggregate compactness, quantified by the fractal dimension, are taken together, we find that highly compact and narrowly distributed aggregate size are characteristics of fSWNTs that result in reduced cytotoxicity. The results presented here suggest that surface functionalization has an indirect effect on the bacterial cytotoxicity of SWNTs through the impact on aggregation state, both dispersity and morphology.
The nature of basic sites on carbon surfaces is a controversial issue within Carbon Science. Traditionally, oxygen-containing groups like: γ pyrone-type, chromene, diketone or quinone groups, on the one hand, and delocalized π-electrons of the basal planes, on the other, are assumed to have a basic nature. However, there is no consensus about neither the strength as bases of these sites, nor the extent of their contribution to the overall carbon basicity. Researchers are divided between those that support basic-oxygen-containing groups as main responsible of carbon basicity and those that attribute the overall basicity of a carbon to the delocalized π-electrons of the basal planes. In this work we will discuss the virtues and drawbacks of the different hypotheses about basic carbon sites in view of experimental and theoretical results.
The proposed mechanisms for O2 reduction on various catalysts are discussed, taking into account the possible role of superoxide radicals, hydogen peroxide and adsorbed dioxygen. Particular attention is focused on O2 reduction on carbon and graphite (both with and without surface modifications), the anomalous temperature dependence of the Tafel slope for O2 reduction on Pt, transition metal macrocycles and heat treated macrocycles. The latter offer considerable promise as O2 reduction catalysts combining high activity with good stability.
Using scattering methods, we determine the morphology of carbon nanotube suspensions over length scales from 1 nm to 50 μm. We find no evidence of rod-like character at any length. Rather, a network structure of aggregated tubes, similar to that seen in dry samples, is found. These observations have significant implications regarding the use of single-walled nanotubes as a composite reinforcing filler since the network structure has significantly lower modulus than fully dispersed tubes. We also show that it is possible to isolate a rod-like fraction from the aggregated suspension using intense sonication, providing a potential route to fully dispersed nanotubes.
A NORIT activated carbon was modified by different chemical and thermal treatments (including oxidation in the gas and liquid phases) in order to obtain materials with different surface properties. Several techniques were used to characterize these materials including nitrogen adsorption, chemical and thermal analyses, XPS, TPD and DRIFTS. The results obtained by TPD agree quantitatively with the elemental and proximate analyses of the oxidized materials, and qualitatively with the observations by DRIFTS. A simple deconvolution method is proposed to analyse the TPD spectra, allowing for the quantitative determination of the amount of each functional group on the surface. A multiple gaussian function has been shown to fit the data adequately, the parameters obtained for each fit matching very well the features observed in the experimentally determined TPD spectra.It is shown that gas phase oxidation of the carbon increases mainly the concentration of hydroxyl and carbonyl surface groups, while oxidations in the liquid phase increase especially the concentration of carboxylic acids.
Direct injection of long multiwalled carbon nanotubes into the abdominal cavity of mice produces asbestos-like pathogenic behaviour. What does this finding mean for nanotube safety?
The challenge of optimizing both performance and safety in nanomaterials hinges on our ability to resolve which structural features lead to desired properties. It has been difficult to draw meaningful conclusions about biological impacts from many studies of nanomaterials due to the lack of nanomaterial characterization, unknown purity, and/or alteration of the nanomaterials by the biological environment. To investigate the relative influence of core size, surface chemistry, and charge on nanomaterial toxicity, we tested the biological response of whole animals exposed to a matrix of nine structurally diverse, precision-engineered gold nanoparticles (AuNPs) of high purity and known composition. Members of the matrix include three core sizes and four unique surface coatings that include positively and negatively charged headgroups. Mortality, malformations, uptake, and elimination of AuNPs were all dependent on these parameters, showing the need for tightly controlled experimental design and nanomaterial characterization. Results presented herein illustrate the value of an integrated approach to identify design rules that minimize potential hazard.
Nanotoxicology studies require investigations of several physico-chemical aspects of the particle/body fluid interaction, here described by reviewing recent literature in the light of new experimental data. Current characterization mostly covers morphology and metric-related characteristics (form, chemical composition, specific surface area, primary particle size and size distribution), and is mandatory in any experimental study. To unveil toxicity mechanisms, several other physico-chemical properties relevant to (geno) toxicity need to be assessed, typically the release or quenching of radical/ROS (Reactive Oxygen Species), the presence of active metal ions, evidence of structural defects. Major tasks for physical chemists working on nanoparticles-induced genotoxicity are described with some examples: (i), Tailored preparation of the same material in different sizes; (ii) particle modification changing a single property at a time; and (iii) identification of appropriate reference materials. Phenomena occurring during the contact between nanoparticles and cellular media or biological fluids (dispersion, agglomeration/aggregation, protein adsorption) are discussed in relation to the surface properties of the nanoparticles considered.
Single-walled carbon nanotubes (SWNTs) have been previously observed to be strong antimicrobial agents, and SWNT coatings can significantly reduce biofilm formation. However, the SWNT antimicrobial mechanism is not fully understood. Previous studies on SWNT cytotoxicity have concluded that membrane stress (i.e., direct SWNT-bacteria contact resulting in membrane perturbation and the release of intracellular contents) was the primary cause of cell death. Gene expression studies have indicated oxidative stress may be active, as well. Here, it is demonstrated for the first time how SWNT electronic structure (i.e., metallic versus semiconducting) is a key factor regulating SWNT antimicrobial activity. Experiments were performed with well-characterized SWNTs of similar length and diameter but varying fraction of metallic nanotubes. Loss of Escherichia coli viability was observed to increase with an increasing fraction of metallic SWNTs. Time-dependent cytotoxicity measurements indicated that in all cases the majority of the SWNT antimicrobial action occurs shortly after (<15 min) bacteria-SWNT contact. The SWNT toxicity mechanism was investigated by in vitro SWNT-mediated oxidation of glutathione, a common intracellular thiol that serves as an antioxidant and redox state mediator. The extent of glutathione oxidation was observed to increase with increasing fraction of metallic SWNTs, indicating an elevated role of oxidative stress. Scanning electron microscopy images of E. coli in contact with the SWNTs demonstrated electronic structure-dependent morphological changes consistent with cytotoxicity and glutathione oxidation results. A three-step SWNT antimicrobial mechanism is proposed involving (i) initial SWNT-bacteria contact, (ii) perturbation of the cell membrane, and (iii) electronic structure-dependent bacterial oxidation.
This critical review of the available human health safety data, relating to carbon nanotubes (CNTs), was conducted in order to assess the risks associated with CNT exposure. Determining the toxicity related to CNT exploitation is of great relevance and importance due to the increased potential for human exposure to CNTs within occupational, environmental and consumer settings. When this information is combined with knowledge on the likely exposure levels of humans to CNTs, it will enable risk assessments to be conducted to assess the risks posed to human health. CNTs are a diverse group of materials and vary with regards to their wall number (single and multi-walled CNTs are evident), length, composition, and surface chemistry. The attributes of CNTs that were identified as being most likely to drive the observed toxicity have been considered, and include CNT length, metal content, tendency to aggregate/agglomerate and surface chemistry. Of particular importance, is the contribution of the fibre paradigm to CNT toxicity, whereby the length of CNTs appears to be critical to their toxic potential. Mechanistic processes that are critical to CNT toxicity will also be discussed, with the findings insinuating that CNTs can exert an oxidative response that stimulates inflammatory, genotoxic and cytotoxic consequences. Consequently, it may transpire that a common mechanism is responsible for driving CNT toxicity, despite the fact that CNTs are a diverse population of materials. The similarity of the structure of CNTs to that of asbestos has prompted concern surrounding the exposure of humans, and so the applicability of the fibre paradigm to CNTs will be evaluated. It is also necessary to determine the systemic availability of CNTs following exposure, to determine where potential targets of toxicity are, and to thereby direct in vitro investigations within the most appropriate target cells. CNTs are therefore a group of materials whose useful exploitable properties prompts their increased production and utilization within diverse applications, so that ensuring their safety is of vital importance.
The ever-increasing use of engineered nanomaterials will lead to heightened levels of these materials in the environment. The present review aims to provide a comprehensive overview of current knowledge regarding nanoparticle transport and aggregation in aquatic environments. Nanoparticle aggregation and deposition behavior will dictate particle transport potential and thus the environmental fate and potential ecotoxicological impacts of these materials. In this review, colloidal forces governing nanoparticle deposition and aggregation are outlined. Essential equations used to assess particle-particle and particle-surface interactions, along with Hamaker constants for specific nanoparticles and the attributes exclusive to nanoscale particle interactions, are described. Theoretical and experimental approaches for evaluating nanoparticle aggregation and deposition are presented, and the major findings of laboratory studies examining these processes are also summarized. Finally, we describe some of the challenges encountered when attempting to quantify the transport of nanoparticles in aquatic environments.
Nanotechnology is a rapidly growing industry of global economic importance, exploiting the novel characteristics of materials manufactured at the nanoscale. The properties of engineered nanoparticles (ENPs) that make them useful in a wide range of industrial applications, however, have led to concerns regarding their potential impact on human and environmental health. The aquatic environment is particularly at risk of exposure to ENPs, as it acts as a sink for most environmental contaminants. This paper critically evaluates what is currently known about sources and discharge of ENPs to the aquatic environment and how the physicochemical characteristics of ENPs affect their fate and behaviour and thus availability for uptake into aquatic organisms, and assesses reported toxicological effects. Having reviewed the ecotoxicological information, the conclusion is that whilst there are data indicating some nanoparticles have the potential to induce harm in exposed aquatic organisms, there is insufficient evidence for harm, for known/modelled environmental concentrations for almost all ENPs considered. This conclusion, however, must be balanced by the fact that there are significant gaps in our understanding on the fate and behaviour of ENPs in the aquatic environment. Greater confidence in the assessments on ENP impacts in aquatic systems to enable effective comparisons across studies urgently requires more standardised approaches for ENP hazard identification, and critically, more thorough characterisations on the exposed particles. There is also an urgent need for the advancement of tools and techniques that can accurately quantify and visualise uptake of nanoparticles into biological tissues.
To further our understanding on the antibacterial activity of single-walled carbon nanotubes (SWCNTs), high purity SWCNTs with average diameter of 0.83 nm and (7,5) chirality as dominate (n,m) structure were dispersed in a biocompatible surfactant solution. Ultraviolet-visible-near-infrared radiation absorption spectroscopy was employed to monitor the aggregation of SWCNTs. The results demonstrated that individually dispersed SWCNTs were more toxic than SWCNT aggregates toward bacteria (gram-negative Escherichia coli, Pseudomonas aeruginosa, and gram-positive Staphylococcus aureus, Bacillus subtilis). Individually dispersed SWCNTs can be visualized as numerous moving "nano darts" in the solution, constantly attacking the bacteria; thereby, degrading the bacterial cell integrity and causing the cell death. Controlled experimental results suggested that inhibiting cell growth and oxidative stress were not the major causes responsible for the death of cells. Furthermore, the detrimental effects of Co metal residues (up to 1 mug/mL) on SWCNT samples can be ruled out. Atomic force microscope study conducted in suspension proved that the death rates of bacteria were strongly correlated with their mechanical properties; soft cells were more vulnerable to SWCNT piercing. The antibacterial activity of SWCNTs can be remarkably improved by enhancing the SWCNT physical puncture on bacteria in the following ways: (1) dispersing SWCNTs individually to sharpen the nano darts; (2) increasing SWCNT concentration to raise the population density of nano darts; and (3) elevating the shaking speed of incubation to speed up the nano darts. This study elucidated several factors controlling the antibacterial activity of pristine SWCNTs and it provided an insight in developing strategies that can maximize the SWCNT application potentials while minimizing the health and environment risks.