Nanotoxicology: a perspective and discussion of whether or not in vitro testing is a valid alternative

Despite the many proposed advantages related to nanotechnology, there are increasing concerns as to the potential adverse human health and environmental effects that the production of, and subsequent exposure to nanoparticles (NPs) might pose. In regard to human health, these concerns are founded upon the plethora of knowledge gained from research relating to the effects observed following exposure to environmental air pollution. It is known that increased exposure to environmental air pollution can cause reduced respiratory health, as well as exacerbate pre-existing conditions such as cardiovascular disease and chronic obstructive pulmonary disease. Such disease states have also been associated with exposure to the NP component contained within environmental air pollution, raising concerns as to the effects of NP exposure. It is not only exposure to accidentally produced NPs however, which should be approached with caution. Over the past decades, NPs have been specifically engineered for a wide range of consumer, industrial and technological applications. Due to the inevitable exposure of NPs to humans, owing to their use in such applications, it is therefore imperative that an understanding of how NPs interact with the human body is gained. In vivo research poses a beneficial model for gaining immediate and direct knowledge of human exposure to such xenobiotics. This research outlook however, has numerous limitations. Increased research using in vitro models has therefore been performed, as these models provide an inexpensive and high-throughput alternative to in vivo research strategies. Despite such advantages, there are also various restrictions in regard to in vitro research. Therefore, the aim of this review, in addition to providing a short perspective upon the field of nanotoxicology, is to discuss (1) the advantages and disadvantages of in vitro research and (2) how in vitro research may provide essential information pertaining to the human health risks posed by NP exposur

Phenotypic characterization of human umbilical vein endothelial (ECV304) and urinary carcinoma (T24) cells: Endothelial versus epithelial features

Summary: ECV 304 cells reported as originating from human umbilical vein endothelial cells by spontaneous transformation have been used as a model cell line for endothelia over the last decade. Recently, deoxyribonucleic acid fingerprinting revealed an identical genotype for ECV 304 and T24 cells (urinary bladder carcinoma cell line). In order to resolve the apparent discrepancy between the identical genotype and the fact that ECV304 cells phenotypically show important endothelial characteristics, a comparative study was performed. Immortalized porcine brain microvascular endothelial cells/C1-2, and Madin Darby canine kidney cells were included as typical endothelial and epithelial cells, respectively. Various methods, such as confocal laser scanning microscopy, Western blot, and protein activity tests, were used to study the cell lines. ECV304 and T24 cells differ in criteria, such as growth behavior, cytoarchitecture, tight junction arrangement, transmembrane electrical resistance, and activity of γ-glutamyltransferase. Several endothelial markers (von Willebrand factor, uptake of low-density lipoprotein, vimentin) could clearly be identified in ECV304, but not in T24 cells. Desmoglein and cytokeratin, both known as epithelial markers, were found in ECV304 as well as T24 cells. However, differences were found for the two cell lines with respect to the type of cytokeratin: in ECV304 cells mainly cytokeratin 18 (45 kDa) is found, whereas in T24 cells cytokeratin 8 (52 kDa) is predominant. As we could demonstrate, the ECV 304 cell line exposes many endothelial features which, in view of the scarcity of suitable endothelial cell lines, still make it an attractive in vitro model for endotheli

Nanofibers: Friend or Foe?

Since the early 1990s nanofibers, particularly those of a carbonaceous content [1] have received heightened interest due to their advantageous physico-chemical characteristics (e.g., high strength, stiffness, semi-conductor, increased thermal conductivity and one of the highest Young’s modulus [2]).[...

Diesel exhaust: current knowledge of adverse effects and underlying cellular mechanisms

Diesel engine emissions are among the most prevalent anthropogenic pollutants worldwide, and with the growing popularity of diesel-fueled engines in the private transportation sector, they are becoming increasingly widespread in densely populated urban regions. However, a large number of toxicological studies clearly show that diesel engine emissions profoundly affect human health. Thus the interest in the molecular and cellular mechanisms underlying these effects is large, especially concerning the nature of the components of diesel exhaust responsible for the effects and how they could be eliminated from the exhaust. This review describes the fundamental properties of diesel exhaust as well as the human respiratory tract and concludes that adverse health effects of diesel exhaust not only emerge from its chemical composition, but also from the interplay between its physical properties, the physiological and cellular properties, and function of the human respiratory tract. Furthermore, the primary molecular and cellular mechanisms triggered by diesel exhaust exposure, as well as the fundamentals of the methods for toxicological testing of diesel exhaust toxicity, are described. The key aspects of adverse effects induced by diesel exhaust exposure described herein will be important for regulators to support or ban certain technologies or to legitimate incentives for the development of promising new technologies such as catalytic diesel particle filters

In vitro approaches to assess the hazard of nanomaterials

The rapid development of engineered nanomaterials demands for a fast and reliable assessment of their health hazard potential. A plethora of experimental approaches have been developed and are widely employed in conventional toxicological approaches. However, the specific properties of nanomaterials such as smaller size but larger surface area, and high catalytic reactivity and distinctive optical properties compared to their respective bulk entities, often disable a straightforward use of established in vitro approaches. Herein, we provide an overview of the current state-of the art nanomaterial hazard assessment strategies using in vitro approaches. This perspective has been developed based on a thorough review of over 200 studies employing such methods to assess the biological response upon exposure to a diverse array of nanomaterials. The majority of the studies under review has been, but not limited to, engaged in the European 7th Framework Programme for Research and Technological Development and published in the last five years. Based on the most widely used methods and/or the most relevant biological endpoints, we have provided some general recommendations on the use of the selected approaches which would the most closely mimic realistic exposure scenarios as well as enabling to yield fast, reliable and reproducible data on the nanomaterial-cell response in vitro. In addition, the applicability of the approaches to translate in vitro outcomes to leverage those of in vivo studies has been proposed. It is finally suggested that an improved comprehension of the approaches with its limitations used for nanomaterials' hazard assessment in vitro will improve the interpretation of the existing nanotoxicological data as well as underline the basic principles in understanding interactions of engineered nanomaterials at a cellular level; this all is imperative for their safe-by- design strategies, and should also enable subsequent regulatory approvals

Assessing meso- and microplastic pollution in the Ligurian and Tyrrhenian Seas

As the production of plastic products continues to increase, determining the fate of plastic waste in the environment is of high importance. Densely populated areas, such as Mediterranean coastlines, represent locations of high pollution risk for surrounding environments. Thus, this study aims to assess the abundance, size, and composition of floating meso- and microplastics collected during four weeks in 2018 in the Ligurian and Tyrrhenian Seas. The results show average meso- and microplastic particle concentrations of 28,376 ± 28,917 particles km−2, and an average mass of 268.61 ± 421.18 g km−2. The particle shape ratio was 65% fragments, 19% films, 10% lines, 4% foams, and 2% pellets. Microplastic particles comprised 65% of the sample. Analysis with attenuated total reflection Fourier transform infrared spectroscopy showed predominant polymer types included polyethylene, polypropylene, polystyrene, and polyamide. These data are an important starting point for long-term monitoring of plastic pollution levels within this region

Organometallic cobalamin anticancer derivatives for targeted prodrug delivery via transcobalamin-mediated uptake

Herein we report the synthesis of new water-soluble vitamin B12 prodrugs bearing metal complexes at the β-upper side of the cobalt center. A total of three derivatives with the general design {Co–C[triple bond, length as m-dash]C-bpy–M}, where M represents a cytotoxic metal complex, were prepared and tested for their cytotoxicity against MCF-7 breast cancer cells. The choice of the metal was oriented on the eminent Pt and promising Ru and Re species to demonstrate the general applicability of the approach. The recognition of the derivatives by transcobalamin was demonstrated by competitive displacement assays using rhodamine labeled B12. This compound further served to prepare a dual luminescent probe by orthogonal synthesis with M = ((HCCbpy)Ru(bpy)2)Cl2 and to perform in vitro assays. Cellular imaging experiments allowed us to observe the different compartmentalization of both dyes and thus prove that the species follow the natural cobalamin uptake as well as the self- triggered release of the β-upper complex

Nanomaterials and the human lung: what is known and what must be deciphered to realise their potential advantages?

Due to the constant expansion within the nanotechnology industry in the last decade, nanomaterials are omnipresent in society today. Nanotechnology-based products have numerous different applications ranging from electronic (e.g., advanced memory chips) to industrial (e.g., coatings or composites) to biomedical (e.g., drug delivery systems, diagnostics). Although these new nanomaterials can be found in many “everyday” products, their effects on the human body have still to be investigated in order to identify not only their risk, but also their potential benefits towards human health. Since the lung is commonly thought to be the main portal of entry into the human body for nanomaterials released within the environment, this review will attempt to summarise the current knowledge and understanding of how nanomaterials interact with the respiratory tract. Furthermore, the advantages and disadvantages of different experimental model systems that are commonly used to study this exposure route to the human body will be discussed