Assessment of the toxicity of silver nanoparticles in vitro: A mitochondrial perspective

The major toxicological concern associated with nanomaterials is the fact that some manufactured nanomaterials are redox active, and some particles transport across cell membranes, especially into mitochondria. Thus, evaluation of their toxicity upon acute exposure is essential. In this work, we evaluated the toxicity of silver nanoparticles (40 and 80 nm) and their effects in rat liver mitochondria bioenergetics.Wistar rat liver mitochondria demonstrate alterations in respiration and membrane potential capacities in the presence of either 40 or 80 nm silver nanoparticles. Our data demonstrated a statistically significant decrease in mitochondrial membrane potential, ADP-induced depolarization, and respiratory control ratio (RCR) upon exposure to silver nanoparticles.Our results show that silver nanoparticles cause impairment of mitochondrial function, due mainly to alterations of mitochondrial membrane permeability. This results in an uncoupling effect on the oxidative phosphorylation system. Thus, mitochondrial toxicity may have a central role in the toxicity resulting from exposure to silver nanoparticles.     

Neurotoxicity of nanoscale materials

Nanotechnology has been applied in consumer products and commercial applications, showing a significant impact on almost all industries and all areas of society. Significant evidence indicates that manufactured nanomaterials and combustion-derived nanomaterials elicit toxicity in humans exposed to these nanomaterials. The interaction of the engineered nanomaterials with the nervous system has received much attention in the nanotoxicology field. In this review, the biological effects of metal, metal oxide, and carbon-based nanomaterials on the nervous system are discussed from both in vitro and in vivo studies. The translocation of the nanoparticles through the blood–brain barrier or nose to brain via the olfactory bulb route, oxidative stress, and inflammatory mechanisms of nanomaterials are also reviewed.     

纳米材料诱导肺部疾病及其机制研究进展

随着纳米科技的飞速发展, 纳米材料凭借其独特的理化性能在材料、 工业、 环保、 军事、 医药等多个领域扮 演着重要的角色。纳米材料的生产和使用, 使其不可避免地进入生态系统, 人们可通过环境暴露、 职业暴露和医源 性暴露接触到纳米材料。呼吸系统是纳米材料进入人体的最主要途径。大量研究证实, 吸入的纳米材料主要通过 氧化应激、 炎症反应和离子紊乱等毒性机制对肺造成损伤, 诱导肉芽肿病变、 肺纤维化、 哮喘、 慢性阻塞性肺疾病, 甚 至肺癌等肺部疾病的发生。本文对纳米材料暴露与肺部疾病的关系及其肺毒性作用机制进行简要综述。     

纳米颗粒物对心血管系统的影响及其作用机制研究进展

随着纳米技术的快速发展和纳米材料的大量出现和广泛应用,人们接触纳米材料的机会大大增加。纳米材料将通过环境暴露、职业暴露以及医源性暴露作用于人类,对人类健康产生潜在危害。越来越多的流行病学研究证实,纳米颗粒暴露与心血管疾病的发生发展关系密切。因此,纳米颗粒心血管系统毒性的研究逐渐受到关注,目前国内外学者已经从细胞、动物和流行病等方面开展了大量研究工作,并取得了一定的进展。本文就国内外有关纳米颗粒物心血管系统毒性研究的进展作一简要的综述。     

Ultrahigh reactivity provokes nanotoxicity: explanation of oral toxicity of nano-copper particles

Recently, studies on the biological effects of nanomaterials show signs that some of the manufactured nanoparticles exhibit unexpected toxicity to living organisms. It has previously been reported that the copper particles possess size-depended toxicity. In this paper, we propose that the ultrahigh chemical reactivity of nano-copper results in the specific nanotoxicity which is fully proved by in vitro and in vivo experiment. Using chemical kinetics study (in vitro) and blood gas and plasma electrolytes analysis (in vivo), we found that high reactivity cause the big toxicological difference between small size (23.5 nm) and big size (17 microm). The result is also consistent with biochemistry assay, pathological examination and copper content measurement in renal tissue in vivo. For chemical reactive nanoparticles, metallic nano-copper for instance, both the particles themselves and the resulting product (copper ion) should be fully explored. The nano-copper particles may not compromise the mice directly, however, they lead to the accumulation of excessive alkalescent substance and heavy metal ions (copper ions) culminating the metabolic alkalosis and copper ion overload.     

Toxicity of nanomaterials; an undermined issue

Nanomaterials are employed in extensive variety of commercial products such as electronic components, cosmetics, food, sports equipment, biomedical applications, and medicine. With the increasing utilization of engineered nanomaterials, the potential exposure of human to nanoparticles is rapidly increasing. Nowadays when new nanomaterials with new applications are introduced, mostly good and positive effects are mentioned whereas possible hazards arising from nanosize of the compounds are undermined. Toxicology studies of nanomaterials demonstrate some adverse effects in some human organs such as central nerve system, immune system, and lung. There is lack of complete information about human toxicity and environmental waste of nanomaterials. We aimed to highlight current toxicological concerns of potentially useful nanomaterials which are now used in pharmaceutical and biomedical sciences.     

Introducing a new standardized nanomaterial environmental toxicity screening testing procedure,ISO/TS 20787: aquatic toxicity assessment of manufactured nanomaterials in saltwater Lakes using Artemia sp. nauplii

This paper introduces a new standardized testing procedure for nanomaterial environmental toxicity (International Organization for Standardization/Technical Specification (ISO/TS) 20787): ‘aquatic toxicity assessment of manufactured nanomaterials in saltwater lakes using Artemia sp. Nauplii’ intended to generate more reliable and repeatable aquatic toxicity data testing manufactured nanomaterials, using Artemia sp., to evaluate their possible ecotoxicity in saltwater lake ecosystems. The principles behind testing with Artemia sp. are reviewed and the paper gives an overview of research published between 2009 and 2018 in which manufactured nanomaterials were tested using Artemia sp.     

Cytotoxicity of carbon nanohorns in different human cells of the respiratory system

ABSTRACT

One of the new synthetic carbon-based nanomaterials is carbon nanohorns (CNH). A potential risk for employees of production processes is an unintentional intake of these nanomaterials via inhalation. Once taken up, nanoparticles might interact with cells of different tissues as well as with intercellular substances. These interactions may have far-reaching consequences for human health. Currently, many gaps in available information on the CNH toxicological profile remain. The aim of this study was to determine the cytotoxicity of CNH particles on human epithelial cells of the respiratory system with special consideration given to different particle sizes. In all cell lines, cell viability was reduced after 24 h of exposure up to 60% and metabolic activity as evidenced by mitochondrial activity was lowered to 9% at a concentration of 1 g/L. The three respiratory cell lines differed in their sensitivity. The most robust cells were the bronchial epithelial cells. Further, particle size fractions induced different adverse effect strength, whereby no correlation between particle size fraction and toxicity was found. These findings demonstrate the need for further information regarding the behavior and effect strength of nanomaterial. To avoid the production of new harmful materials, a more comprehensive integration of results from toxicity studies in the development processes of engineered nanomaterials is recommended not only from an occupational viewpoint but also from an environmental perspective.     

Nanoparticles in food. Epigenetic changes induced by nanomaterials and possible impact on health

Disturbed epigenetic mechanisms, which developmentally regulate gene expression via modifications to DNA, histone proteins, and chromatin, have been hypothesized to play a key role in many human diseases. Recently it was shown that engineered nanoparticles (NPs), that already have a wide range of applications in various fields including food production, could dramatically affect epigenetic processes, while their ability to induce diseases remains poorly understood. Besides the obvious benefits of the new technologies, it is critical to assess their health effects before proceeding with industrial production. In this article, after surveying the applications of NPs in food technology, we review recent advances in the understanding of epigenetic pathological effects of NPs, and discuss their possible health impact with the aim of avoiding potential health risks posed by the use of nanomaterials in foods and food-packaging.     

Bisphenol A and its analogs: Do their metabolites have endocrine activity?

Structural analogs of bisphenol A are commonly used as its alternatives in industrial and commercial applications. Nevertheless, the question arises whether the use of other bisphenols is justified as replacements for bisphenol A in mass production of plastic materials. To evaluate the influence of metabolic reactions on endocrine activities of bisphenols, we conducted a systematic review of the literature. Knowledge about the metabolic pathways and enzymes involved in metabolic biotransformations is essential for understanding and predicting mechanisms of toxicity. Bisphenols are metabolized predominantly by the glucuronidation reaction, which is considered their most important detoxification pathway, as based on current knowledge, glucuronides do not have activity on endocrine receptors. In contrast, several oxidative metabolites of bisphenols with enhanced endocrine activities are presented, and these findings indicate that oxidative metabolites of bisphenols can still have endocrine activities in humans.     

In vitro cytotoxicity of nanoparticles in mammalian germline stem cells.

Gametogenesis is a complex biological process that is particularly sensitive to environmental insults such as chemicals. Many chemicals have a negative impact on the germline, either by directly affecting the germ cells, or indirectly through their action on the somatic nursing cells. Ultimately, these effects can inhibit fertility, and they may have negative consequences for the development of the offspring. Recently, nanomaterials such as nanotubes, nanowires, fullerene derivatives (buckyballs), and quantum dots have received enormous national attention in the creation of new types of analytical tools for biotechnology and the life sciences. Despite the wide application of nanomaterials, there is a serious lack of information concerning their impact on human health and the environment. Thus, there are limited studies available on toxicity of nanoparticles for risk assessment of nanomaterials. The purpose of this study was to assess the suitability of a mouse spermatogonial stem cell line as a model to assess nanotoxicity in the male germline in vitro. The effects of different types of nanoparticles on these cells were evaluated by light microscopy, and by cell proliferation and standard cytotoxicity assays. Our results demonstrate a concentration-dependent toxicity for all types of particles tested, whereas the corresponding soluble salts had no significant effect. Silver nanoparticles were the most toxic while molybdenum trioxide (MoO(3)) nanoparticles were the least toxic. Our results suggest that this cell line provides a valuable model with which to assess the cytotoxicity of nanoparticles in the germ line in vitro.     

The ecotoxicology and chemistry of manufactured nanoparticles

The emerging literature on the ecotoxicity of nanoparticles and nanomaterials is summarised, then the fundamental physico-chemistry that governs particle behaviour is explained in an ecotoxicological context. Techniques for measuring nanoparticles in various biological and chemical matrices are also outlined. The emerging ecotoxicological literature shows toxic effects on fish and invertebrates, often at low mg l⁻¹ concentrations of nanoparticles. However, data on bacteria, plants, and terrestrial species are particularly lacking at present. Initial data suggest that at least some manufactured nanoparticles may interact with other contaminants, influencing their ecotoxicity. Particle behaviour is influenced by particle size, shape, surface charge, and the presence of other materials in the environment. Nanoparticles tend to aggregate in hard water and seawater, and are greatly influenced by the specific type of organic matter or other natural particles (colloids) present in freshwater. The state of dispersion will alter ecotoxicity, but many abiotic factors that influence this, such as pH, salinity, and the presence of organic matter remain to be systematically investigated as part of ecotoxicological studies. Concentrations of manufactured nanoparticles have rarely been measured in the environment to date. Various techniques are available to characterise nanoparticles for exposure and dosimetry, although each of these methods has advantages and disadvantages for the ecotoxicologist. We conclude with a consideration of implications for environmental risk assessment of manufactured nanoparticles.     

Toxicology of nanomaterials used in nanomedicine

With the development of nanotechnology, nanomaterials are being widely used in many industries as well as in medicine and pharmacology. Despite the many proposed advantages of nanomaterials, increasing concerns have been expressed on their potential adverse human health effects. In recent years, application of nanotechnology in medicine has been defined as nanomedicine. Techniques in nanomedicine make it possible to deliver therapeutic agents into targeted specific cells, cellular compartments, tissues, and organs by using nanoparticulate carriers. Because nanoparticles possess different physicochemical properties than their fine-sized analogues due to their extremely small size and large surface area, they need to be evaluated separately for toxicity and adverse health effects. In addition, in the field of nanomedicine, intravenous and subcutaneous injections of nanoparticulate carriers deliver exogenous nanoparticles directly into the human body without passing through the normal absorption process. These nanoparticulate carriers themselves may be responsible for toxicity and interaction with biological macromolecules within the human body. Second, insoluble nanoparticulate carriers may accumulate in human tissues or organs. Therefore, it is necessary to address the potential health and safety implications of nanomaterials used in nanomedicine. Toxicological studies for biosafety evaluation of these nanomaterials will be important for the continuous development of nanomedical science. This review summarizes the current knowledge on toxicology of nanomaterials, particularly on those used in nanomedicine.     

Toxicology of Nanomaterials Used in Nanomedicine

With the development of nanotechnology, nanomaterials are being widely used in many industries as well as in medicine and pharmacology. Despite the many proposed advantages of nanomaterials, increasing concerns have been expressed on their potential adverse human health effects. In recent years, application of nanotechnology in medicine has been defined as nanomedicine. Techniques in nanomedicine make it possible to deliver therapeutic agents into targeted specific cells, cellular compartments, tissues, and organs by using nanoparticulate carriers. Because nanoparticles possess different physicochemical properties than their fine-sized analogues due to their extremely small size and large surface area, they need to be evaluated separately for toxicity and adverse health effects. In addition, in the field of nanomedicine, intravenous and subcutaneous injections of nanoparticulate carriers deliver exogenous nanoparticles directly into the human body without passing through the normal absorption process. These nanoparticulate carriers themselves may be responsible for toxicity and interaction with biological macromolecules within the human body. Second, insoluble nanoparticulate carriers may accumulate in human tissues or organs. Therefore, it is necessary to address the potential health and safety implications of nanomaterials used in nanomedicine. Toxicological studies for biosafety evaluation of these nanomaterials will be important for the continuous development of nanomedical science. This review summarizes the current knowledge on toxicology of nanomaterials, particularly on those used in nanomedicine.     

Dispersion, fractionation and characterization of sub-100nm P25 TiO2 nanoparticles in aqueous media

Despite of the widespread use of manufactured nanomaterials and increasing concerns on their potential risk, only limited information is available on their physicochemical properties in toxicologically relavant aqueous media. Here, P25 TiO₂ (Evonik GmbH), one of the well-known and widely-used photocatalytic TiO₂, was dispersed and fractionated in aqueous media, and its physicochemical properties, especially for its sub-100 nm fraction, was carefullly studied. The colloidal properties of TiO₂ nanoparticles, such as ag]glomeration and sedimentation, were found strongly dependent on the physicochemical characteristics of nanoparticles (e.g., hydrodynamic size distribution, type of capping ligands and surface charge) as well as those of the aqueous media used (e.g., ionic strength and chemical compositions). This study has shown the importance of standardized dispersion and characterization protocol for toxicity tests, which is urgently needed for reliable, reproducible and impartial toxicity tests of manufactured nanomaterials.     

Application of nanomedicine in cardiovascular diseases and stroke

Nanomedicine is using nanotechnology in the medical application, which could range from medical use of nanomaterials in drug delivery and bio-imaging to development of nano-scale devices and sensors for diagnosis and therapy. Nanomedicine could also include methods to evaluate nanomaterials solely to ensure safe use through careful monitoring for potential toxicity. In this review, we will outline some of the potential uses of nanotechnology in different fields of medicine with special emphasis on cardiovascular diseases and stroke, based on pathophysiologic basis. We will also review some of the known nanomaterials that are already being utilized in diagnosis and treatment, commonly the FDA approved nanomaterials and others that have demonstrated to be promising in clinical applications.Finally, we will discuss the potential limitations of using nanotechnology in medical applications. Since nanomedicine is now emerging and still in development, this review is not intended as a comprehensive or conclusive overview of nanomedicine. Instead, we hope to provide examples of what are available currently, and to demonstrate the enormous potentials of nanomedicine in order to meet the unresolved needs and new challenges of medicine.     

Mutagenic effects of gold nanoparticles induce aberrant phenotypes in Drosophila melanogaster

The peculiar physical/chemical characteristics of engineered nanomaterials have led to a rapid increase of nanotechnology-based applications in many fields. However, before exploiting their huge and wide potential, it is necessary to assess their effects upon interaction with living systems. In this context, the screening of nanomaterials to evaluate their possible toxicity and understand the underlying mechanisms currently represents a crucial opportunity to prevent severe harmful effects in the next future. In this work we show the in vivo toxicity of gold nanoparticles (Au NPs) in Drosophila melanogaster, highlighting significant genotoxic effects and, thus, revealing an unsettling aspect of the long-term outcome of the exposure to this nanomaterial. After the treatment with Au NPs, we observed dramatic phenotypic modifications in the subsequent generations of Drosophila, demonstrating their capability to induce mutagenic effects that may be transmitted to the descendants. Noteworthy, we were able to obtain the first nanomaterial-mutated organism, named NM-mut. Although these results sound alarming, they underline the importance of systematic and reliable toxicology characterizations of nanomaterials and the necessity of significant efforts by the nanoscience community in designing and testing suitable nanoscale surface engineering/coating to develop biocompatible nanomaterials with no hazardous effects for human health and environment. FROM THE CLINICAL EDITOR: While the clinical application of nanomedicine is still in its infancy, the rapid evolution of this field will undoubtedly result in a growing number of clinical trials and eventually in human applications. The interactions of nanoparticles with living organisms determine their toxicity and long-term safety, which must be properly understood prior to large-scale applications are considered. The paper by Dr. Pompa's team is the first ever demonstration of mutagenesis resulting in clearly observable phenotypic alterations and the generation of nano-mutants as a result of exposure to citrate-surfaced gold nanoparticles in drosophila. These groundbreaking results are alarming, but represent a true milestone in nanomedicine and serve as a a reminder and warning about the critical importance of "safety first" in biomedical science.     

Biopharmaceutics and therapeutic potential of engineered nanomaterials

Engineered nanomaterials are at the leading edge of the rapidly developing nanosciences and are founding an important class of new materials with specific physicochemical properties different from bulk materials with the same compositions. The potential for nanomaterials is rapidly expanding with novel applications constantly being explored in different areas. The unique size-dependent properties of nanomaterials make them very attractive for pharmaceutical applications. Investigations of physical, chemical and biological properties of engineered nanomaterials have yielded valuable information. Cytotoxic effects of certain engineered nanomaterials towards malignant cells form the basis for one aspect of nanomedicine. It is inferred that size, three dimensional shape, hydrophobicity and electronic configurations make them an appealing subject in medicinal chemistry. Their unique structure coupled with immense scope for derivatization forms a base for exciting developments in therapeutics. This review article addresses the fate of absorption, distribution, metabolism and excretion (ADME) of engineered nanoparticles in vitro and in vivo. It updates the distinctive methodology used for studying the biopharmaceutics of nanoparticles. This review addresses the future potential and safety concerns and genotoxicity of nanoparticle formulations in general. It particularly emphasizes the effects of nanoparticles on metabolic enzymes as well as the parenteral or inhalation administration routes of nanoparticle formulations. This paper illustrates the potential of nanomedicine by discussing biopharmaceutics of fullerene derivatives and their suitability for diagnostic and therapeutic purposes. Future direction is discussed as well.     

Applying quantitative structure–activity relationship approaches to nanotoxicology: Current status and future potential

The potential (eco)toxicological hazard posed by engineered nanoparticles is a major scientific and societal concern since several industrial sectors (e.g. electronics, biomedicine, and cosmetics) are exploiting the innovative properties of nanostructures resulting in their large-scale production. Many consumer products contain nanomaterials and, given their complex life-cycle, it is essential to anticipate their (eco)toxicological properties in a fast and inexpensive way in order to mitigate adverse effects on human health and the environment. In this context, the application of the structure–toxicity paradigm to nanomaterials represents a promising approach. Indeed, according to this paradigm, it is possible to predict toxicological effects induced by chemicals on the basis of their structural similarity with chemicals for which toxicological endpoints have been previously measured. These structure–toxicity relationships can be quantitative or qualitative in nature and they can predict toxicological effects directly from the physicochemical properties of the entities (e.g. nanoparticles) of interest. Therefore, this approach can aid in prioritizing resources in toxicological investigations while reducing the ethical and monetary costs that are related to animal testing. The purpose of this review is to provide a summary of recent key advances in the field of QSAR modelling of nanomaterial toxicity, to identify the major gaps in research required to accelerate the use of quantitative structure–activity relationship (QSAR) methods, and to provide a roadmap for future research needed to achieve QSAR models useful for regulatory purposes.