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In vitro cell models offer a unique opportunity for conducting toxicology research, and the human lung adenocarcinoma cell line A549 is commonly used for toxicology testing strategies. It is essential to determine whether the response of these cells grown in different laboratories is consistent. In this study, A549 cells were grown under both submerged and air-liquid interface (ALI) conditions following an identical cell seeding protocol in two independent laboratories. The cells were switched to the ALI after four days of submerged growth, and their behaviour was compared to submerged conditions. The membrane integrity, cell viability, morphology, and (pro-)inflammatory response upon positive control stimuli were assessed at days 3, 5, and 7 under submerged conditions and at days 5, 7, and 10 at the ALI. Due to the high variability of the results between the two laboratories, the experiment was subsequently repeated using identical reagents at one specific time point and condition (day 5 at the ALI). Despite some variability, the results were more comparable, proving that the original protocol necessitated improvements. In conclusion, the use of detailed protocols and consumables from the same providers, special training of personnel for cell handling, and endpoint analysis are critical to obtain reproducible results across independent laboratories.
Hana Barosova; Kirsty Meldrum; Bedia Begum Karakocak; Sandor Balog; Shareen H. Doak; Alke Petri-Fink; Martin J.D. Clift; Barbara Rothen-Rutishauser. Inter-laboratory variability of A549 epithelial cells grown under submerged and air-liquid interface conditions. Toxicology in Vitro 2021, 75, 105178 .
AMA StyleHana Barosova, Kirsty Meldrum, Bedia Begum Karakocak, Sandor Balog, Shareen H. Doak, Alke Petri-Fink, Martin J.D. Clift, Barbara Rothen-Rutishauser. Inter-laboratory variability of A549 epithelial cells grown under submerged and air-liquid interface conditions. Toxicology in Vitro. 2021; 75 ():105178.
Chicago/Turabian StyleHana Barosova; Kirsty Meldrum; Bedia Begum Karakocak; Sandor Balog; Shareen H. Doak; Alke Petri-Fink; Martin J.D. Clift; Barbara Rothen-Rutishauser. 2021. "Inter-laboratory variability of A549 epithelial cells grown under submerged and air-liquid interface conditions." Toxicology in Vitro 75, no. : 105178.
Martin J. D. Clift; Shareen H. Doak. Advanced In Vitro Models for Replacement of Animal Experiments. Small 2021, 17, 2101474 .
AMA StyleMartin J. D. Clift, Shareen H. Doak. Advanced In Vitro Models for Replacement of Animal Experiments. Small. 2021; 17 (15):2101474.
Chicago/Turabian StyleMartin J. D. Clift; Shareen H. Doak. 2021. "Advanced In Vitro Models for Replacement of Animal Experiments." Small 17, no. 15: 2101474.
Background Toxicological evaluation of engineered nanomaterials (ENMs) is essential for occupational health and safety, particularly where bulk manufactured ENMs such as few-layer graphene (FLG) are concerned. Additionally, there is a necessity to develop advanced in vitro models when testing ENMs to provide a physiologically relevant alternative to invasive animal experimentation. The aim of this study was to determine the genotoxicity of non-functionalised (neutral), amine- and carboxyl-functionalised FLG upon both human-transformed type-I (TT1) alveolar epithelial cell monocultures, as well as co-cultures of TT1 and differentiated THP-1 monocytes (d.THP-1 (macrophages)). Results In monocultures, TT1 and d.THP-1 macrophages showed a statistically significant (p < 0.05) cytotoxic response with each ENM following 24-h exposures. Monoculture genotoxicity measured by the in vitro cytokinesis blocked micronucleus (CBMN) assay revealed significant (p < 0.05) micronuclei induction at 8 µg/ml for amine- and carboxyl-FLG. Transmission electron microscopy (TEM) revealed ENMs were internalised by TT1 cells within membrane-bound vesicles. In the co-cultures, ENMs induced genotoxicity in the absence of cytotoxic effects. Co-cultures pre-exposed to 1.5 mM N-acetylcysteine (NAC), showed baseline levels of micronuclei induction, indicating that the genotoxicity observed was driven by oxidative stress. Conclusions Therefore, FLG genotoxicity when examined in monocultures, results in primary-indirect DNA damage; whereas co-cultured cells reveal secondary mechanisms of DNA damage.
Michael J. Burgum; Martin J. D. Clift; Stephen J. Evans; Nicole Hondow; Afshin Tarat; Gareth J. Jenkins; Shareen H. Doak. Few-layer graphene induces both primary and secondary genotoxicity in epithelial barrier models in vitro. Journal of Nanobiotechnology 2021, 19, 1 -15.
AMA StyleMichael J. Burgum, Martin J. D. Clift, Stephen J. Evans, Nicole Hondow, Afshin Tarat, Gareth J. Jenkins, Shareen H. Doak. Few-layer graphene induces both primary and secondary genotoxicity in epithelial barrier models in vitro. Journal of Nanobiotechnology. 2021; 19 (1):1-15.
Chicago/Turabian StyleMichael J. Burgum; Martin J. D. Clift; Stephen J. Evans; Nicole Hondow; Afshin Tarat; Gareth J. Jenkins; Shareen H. Doak. 2021. "Few-layer graphene induces both primary and secondary genotoxicity in epithelial barrier models in vitro." Journal of Nanobiotechnology 19, no. 1: 1-15.
Summary Immunotherapy has yielded impressive results, but only for a minority of patients with cancer. Therefore, new approaches that potentiate immunotherapy are a pressing medical need. Ferroptosis is a newly described type of programmed cell death driven by iron-dependent phospholipid peroxidation via Fenton chemistry. Here, we developed iron oxide-loaded nanovaccines (IONVs), which, chemically programmed to integrate iron catalysis, drug delivery, and tracking exploiting the characteristics of the tumor microenvironment (TME), improves immunotherapy and activation of ferroptosis. The IONVs trigger danger signals and use molecular disassembly and reversible covalent bonds for targeted antigen delivery and improved immunostimulatory capacity and catalytic iron for targeting tumor cell ferroptosis. IONV- and antibody-mediated TME modulation interfaced with imaging was important toward achieving complete eradication of aggressive and established tumors, eliciting long-lived protective antitumor immunity with no toxicities. This work establishes the feasibility of using nanoparticle iron catalytic activity as a versatile and effective feature for enhancing immunotherapy.
Ane Ruiz-De-Angulo; Marc Bilbao-Asensio; James Cronin; Stephen J. Evans; Martin J.D. Clift; Jordi Llop; Irene V.J. Feiner; Rhiannon Beadman; Kepa Zamacola Bascarán; Juan C. Mareque-Rivas. Chemically Programmed Vaccines: Iron Catalysis in Nanoparticles Enhances Combination Immunotherapy and Immunotherapy-Promoted Tumor Ferroptosis. iScience 2020, 23, 101499 .
AMA StyleAne Ruiz-De-Angulo, Marc Bilbao-Asensio, James Cronin, Stephen J. Evans, Martin J.D. Clift, Jordi Llop, Irene V.J. Feiner, Rhiannon Beadman, Kepa Zamacola Bascarán, Juan C. Mareque-Rivas. Chemically Programmed Vaccines: Iron Catalysis in Nanoparticles Enhances Combination Immunotherapy and Immunotherapy-Promoted Tumor Ferroptosis. iScience. 2020; 23 (9):101499.
Chicago/Turabian StyleAne Ruiz-De-Angulo; Marc Bilbao-Asensio; James Cronin; Stephen J. Evans; Martin J.D. Clift; Jordi Llop; Irene V.J. Feiner; Rhiannon Beadman; Kepa Zamacola Bascarán; Juan C. Mareque-Rivas. 2020. "Chemically Programmed Vaccines: Iron Catalysis in Nanoparticles Enhances Combination Immunotherapy and Immunotherapy-Promoted Tumor Ferroptosis." iScience 23, no. 9: 101499.
To elucidate the impact of human exposure to engineered nanomaterials, advanced in vitro models are a valid non‐animal alternative. Despite significant gains over the last decade, implementation of these approaches remains limited. This work discusses the current state‐of‐the‐art and how future developments can lead to advanced in vitro models better supporting nano‐hazard assessment.
Martin J. D. Clift; Gareth J. S. Jenkins; Shareen H. Doak. An Alternative Perspective towards Reducing the Risk of Engineered Nanomaterials to Human Health. Small 2020, 16, e2002002 .
AMA StyleMartin J. D. Clift, Gareth J. S. Jenkins, Shareen H. Doak. An Alternative Perspective towards Reducing the Risk of Engineered Nanomaterials to Human Health. Small. 2020; 16 (36):e2002002.
Chicago/Turabian StyleMartin J. D. Clift; Gareth J. S. Jenkins; Shareen H. Doak. 2020. "An Alternative Perspective towards Reducing the Risk of Engineered Nanomaterials to Human Health." Small 16, no. 36: e2002002.
Human exposure to engineered nanomaterials (ENMs) is inevitable due to the plethora of applications they are being manufactured for and integrated within. ENMs demonstrate plentiful advantages in terms of industrial approaches, as well as from a consumer perspective. However, despite such positives, doubts remain over the human health implications of ENM exposure. In light of the increased research focus upon the potential effects of ENM exposure to human health in recent decades, questions still remain regarding the safety of these highly advanced, precision-tuned physical entities. The risk of short-term, high-dose exposure to humans is considered relatively low, although this has formed the direction of the hazard-assessment community since the turn of the 21st century. However, the possibility of humans being exposed repeatedly over a long period of time to low-dose ENMs of varying physico-chemical characteristics is of significant concern, and thus the attentions of industry, government, academic and consumer agencies are only now beginning to consider this. Notably, when considering the human health implications of such low-dose, long-term, repeated exposure scenarios the impact of ENMs upon the human immune system is a primary importance. However, there remains a real need to understand the impact of ENMs upon the human immune system, especially the innate immune system, at all stages of life, given exposure to nano-sized particles begins before birth, i.e. of the fetus. Therefore, the purpose of this perspective is to summarise what is currently known regarding ENM exposure of different components of the innate immune system and identify knowledge gaps that should be addressed if we are to fully deduce the impact of ENM exposure on immune function.
James G. Cronin; Nicholas Jones; Catherine A. Thornton; Gareth J. S. Jenkins; Shareen H. Doak; Martin James David Clift. Nanomaterials and Innate Immunity: A Perspective of the Current Status in Nanosafety. Chemical Research in Toxicology 2020, 33, 1061 -1073.
AMA StyleJames G. Cronin, Nicholas Jones, Catherine A. Thornton, Gareth J. S. Jenkins, Shareen H. Doak, Martin James David Clift. Nanomaterials and Innate Immunity: A Perspective of the Current Status in Nanosafety. Chemical Research in Toxicology. 2020; 33 (5):1061-1073.
Chicago/Turabian StyleJames G. Cronin; Nicholas Jones; Catherine A. Thornton; Gareth J. S. Jenkins; Shareen H. Doak; Martin James David Clift. 2020. "Nanomaterials and Innate Immunity: A Perspective of the Current Status in Nanosafety." Chemical Research in Toxicology 33, no. 5: 1061-1073.
It is my absolute pleasure to take up the position of Editor-in-Chief (EiC) of
Martin J. D. Clift. Fibrous Material Science: Extensive and Persistent. Fibers 2020, 8, 16 .
AMA StyleMartin J. D. Clift. Fibrous Material Science: Extensive and Persistent. Fibers. 2020; 8 (2):16.
Chicago/Turabian StyleMartin J. D. Clift. 2020. "Fibrous Material Science: Extensive and Persistent." Fibers 8, no. 2: 16.
The overt hazard of carbon nanotubes (CNTs) is often assessed using in vitro methods, but determining a dose–response relationship is still a challenge due to the analytical difficulty of quantifying the dose delivered to cells. An approach to accurately quantify CNT doses for submerged in vitro adherent cell culture systems using UV-VIS-near-infrared (NIR) spectroscopy is provided here. Two types of multi-walled CNTs (MWCNTs), Mitsui-7 and Nanocyl, which are dispersed in protein rich cell culture media, are studied as tested materials. Post 48 h of CNT incubation, the cellular fractions are subjected to microwave-assisted acid digestion/oxidation treatment, which eliminates biological matrix interference and improves CNT colloidal stability. The retrieved oxidized CNTs are analyzed and quantified using UV-VIS-NIR spectroscopy. In vitro imaging and quantification data in the presence of human lung epithelial cells (A549) confirm that up to 85% of Mitsui-7 and 48% for Nanocyl sediment interact (either through internalization or adherence) with cells during the 48 h of incubation. This finding is further confirmed using a sedimentation approach to estimate the delivered dose by measuring the depletion profile of the CNTs.
Dedy Septiadi; Laura Rodriguez-Lorenzo; Sandor Balog; Miguel Spuch-Calvar; Giovanni Spiaggia; Patricia Taladriz-Blanco; Hana Barosova; Savvina Chortarea; Martin J. D. Clift; Justin Teeguarden; Monita Sharma; Alke Petri-Fink; Barbara Rothen-Rutishauser. Quantification of Carbon Nanotube Doses in Adherent Cell Culture Assays Using UV-VIS-NIR Spectroscopy. Nanomaterials 2019, 9, 1765 .
AMA StyleDedy Septiadi, Laura Rodriguez-Lorenzo, Sandor Balog, Miguel Spuch-Calvar, Giovanni Spiaggia, Patricia Taladriz-Blanco, Hana Barosova, Savvina Chortarea, Martin J. D. Clift, Justin Teeguarden, Monita Sharma, Alke Petri-Fink, Barbara Rothen-Rutishauser. Quantification of Carbon Nanotube Doses in Adherent Cell Culture Assays Using UV-VIS-NIR Spectroscopy. Nanomaterials. 2019; 9 (12):1765.
Chicago/Turabian StyleDedy Septiadi; Laura Rodriguez-Lorenzo; Sandor Balog; Miguel Spuch-Calvar; Giovanni Spiaggia; Patricia Taladriz-Blanco; Hana Barosova; Savvina Chortarea; Martin J. D. Clift; Justin Teeguarden; Monita Sharma; Alke Petri-Fink; Barbara Rothen-Rutishauser. 2019. "Quantification of Carbon Nanotube Doses in Adherent Cell Culture Assays Using UV-VIS-NIR Spectroscopy." Nanomaterials 9, no. 12: 1765.
Volcanic plumes are complex environments composed of gases and ash particles, where chemical and physical processes occur at different temperature and compositional regimes. Commonly, soluble sulphate- and chloride-bearing salts are formed on ash as gases interact with ash surfaces. Exposure to respirable volcanic ash following an eruption is potentially a significant health concern. The impact of such gas-ash interactions on ash toxicity is wholly un-investigated. Here, we study, for the first time, whether the interaction of volcanic particles with sulphur dioxide (SO2) gas, and the resulting presence of sulphate salt deposits on particle surfaces, influences toxicity to the respiratory system, using an advanced in vitro approach. To emplace surface sulphate salts on particles, via replication of the physicochemical reactions that occur between pristine ash surfaces and volcanic gas, analogue substrates (powdered synthetic volcanic glass and natural pumice) were exposed to SO2 at 500 °C, in a novel Advanced Gas-Ash Reactor, resulting in salt-laden particles. The solubility of surface salt deposits was then assessed by leaching in water and geochemical modelling. A human multicellular lung model was exposed to aerosolised salt-laden and pristine (salt-free) particles, and incubated for 24 h. Cell cultures were subsequently assessed for biological endpoints, including cytotoxicity (lactate dehydrogenase release), oxidative stress (oxidative stress-related gene expression; heme oxygenase 1 and NAD(P)H dehydrogenase [quinone] 1) and its (pro-)inflammatory response (tumour necrosis factor α, interleukin 8 and interleukin 1β at gene and protein levels). In the lung cell model no significant effects were observed between the pristine and SO2-exposed particles, indicating that the surface salt deposits, and the underlying alterations to the substrate, do not cause acute adverse effects in vitro. Based on the leachate data, the majority of the sulphate salts from the ash surfaces are likely to dissolve in the lungs prior to cellular uptake. The findings of this study indicate that interaction of volcanic ash with SO2 during ash generation and transport does not significantly affect the respiratory toxicity of volcanic ash in vitro. Therefore, sulphate salts are unlikely a dominant factor controlling variability in in vitro toxicity assessments observed during previous eruption response efforts.
Ines Tomašek; David E. Damby; Claire J. Horwell; Paul M. Ayris; Pierre Delmelle; Christopher J. Ottley; Pablo Cubillas; Ana S. Casas; Christoph Bisig; Alke Petri-Fink; Donald B. Dingwell; Martin Clift; Barbara Drasler; Barbara Rothen-Rutishauser. Assessment of the potential for in-plume sulphur dioxide gas-ash interactions to influence the respiratory toxicity of volcanic ash. Environmental Research 2019, 179, 108798 .
AMA StyleInes Tomašek, David E. Damby, Claire J. Horwell, Paul M. Ayris, Pierre Delmelle, Christopher J. Ottley, Pablo Cubillas, Ana S. Casas, Christoph Bisig, Alke Petri-Fink, Donald B. Dingwell, Martin Clift, Barbara Drasler, Barbara Rothen-Rutishauser. Assessment of the potential for in-plume sulphur dioxide gas-ash interactions to influence the respiratory toxicity of volcanic ash. Environmental Research. 2019; 179 ():108798.
Chicago/Turabian StyleInes Tomašek; David E. Damby; Claire J. Horwell; Paul M. Ayris; Pierre Delmelle; Christopher J. Ottley; Pablo Cubillas; Ana S. Casas; Christoph Bisig; Alke Petri-Fink; Donald B. Dingwell; Martin Clift; Barbara Drasler; Barbara Rothen-Rutishauser. 2019. "Assessment of the potential for in-plume sulphur dioxide gas-ash interactions to influence the respiratory toxicity of volcanic ash." Environmental Research 179, no. : 108798.
Gold nanoparticles (GNPs) are intended for use within a variety of biomedical applications due to their physicochemical properties. Although, in general, biocompatibility of GNPs with immune cells such as macrophages and dendritic cells is well established, the impact of GNPs on B lymphocyte immune function remains to be determined. Since B lymphocytes play an important role in health and disease, the suitability of GNPs as a B cell-targeting tool is of high relevance. Thus, we provide information on the interactions of GNPs with B lymphocytes. Herein, we exposed freshly isolated human B lymphocytes to a set of well-characterized and biomedically relevant GNPs with distinct surface (polyethylene glycol (PEG), PEG/poly(vinyl alcohol) (PEG/PVA)) and shape (spheres, rods) characteristics. Polymer-coated GNPs poorly interacted with B lymphocytes, in contrast to uncoated GNPs. Importantly, none of the GNPs significantly affected cell viability, even at the highest concentration of 20 μg/mL over a 24 h suspension exposure period. Furthermore, none of the nanosphere formulations affected the expression of activation markers (CD69, CD86, MHC II) of the naive B lymphocytes, nor did they cause an increase in the secretion of pro-inflammatory cytokines ( i.e. , IL-6, IL-1β). However, the absence of polymer coating on the sphere GNPs and the rod shape caused a decrease in IL-6 cytokine production by activated B lymphocytes, suggesting a functional impairment. With these findings, the present study contributes imperative knowledge toward the safe-by-design approaches being conducted to benefit the development of nanomaterials, specifically those as theranostic tools.
Sandra Hočevar; Ana Milosevic; Laura Rodriguez-Lorenzo; Liliane Ackermann-Hirschi; Ines Mottas; Alke Petri-Fink; Barbara Rothen-Rutishauser; Carole Bourquin; Martin James David Clift. Polymer-Coated Gold Nanospheres Do Not Impair the Innate Immune Function of Human B Lymphocytes in Vitro. ACS Nano 2019, 13, 6790 -6800.
AMA StyleSandra Hočevar, Ana Milosevic, Laura Rodriguez-Lorenzo, Liliane Ackermann-Hirschi, Ines Mottas, Alke Petri-Fink, Barbara Rothen-Rutishauser, Carole Bourquin, Martin James David Clift. Polymer-Coated Gold Nanospheres Do Not Impair the Innate Immune Function of Human B Lymphocytes in Vitro. ACS Nano. 2019; 13 (6):6790-6800.
Chicago/Turabian StyleSandra Hočevar; Ana Milosevic; Laura Rodriguez-Lorenzo; Liliane Ackermann-Hirschi; Ines Mottas; Alke Petri-Fink; Barbara Rothen-Rutishauser; Carole Bourquin; Martin James David Clift. 2019. "Polymer-Coated Gold Nanospheres Do Not Impair the Innate Immune Function of Human B Lymphocytes in Vitro." ACS Nano 13, no. 6: 6790-6800.
In response to the significant increase in nanotechnology over the last three decades, and the plethora of engineered nanomaterials (ENMs) now becoming available, understanding as to how nano-sized particles may impact upon human health has become a dominating area of research worldwide since the late 1990’s (Stone et al. in Environmental Health Perspectives, 2017) [1]. Whilst approaches constantly adapt to the increasing number and variety of ENMs produced for a plethora of different applications, the quantity of alternative physico-chemical characteristics, a key factor in the potential hazard of ENMs (Bouwmeester et al. in Nanotoxicology 5:1–11, 2011) [2], is further increasing in number and type.
Stephen Evans; Gareth J. Jenkins; Shareen H. Doak; Martin J. D. Clift. Cellular Defense Mechanisms Following Nanomaterial Exposure: A Focus on Oxidative Stress and Cytotoxicity. 2D Nanoelectronics 2019, 243 -254.
AMA StyleStephen Evans, Gareth J. Jenkins, Shareen H. Doak, Martin J. D. Clift. Cellular Defense Mechanisms Following Nanomaterial Exposure: A Focus on Oxidative Stress and Cytotoxicity. 2D Nanoelectronics. 2019; ():243-254.
Chicago/Turabian StyleStephen Evans; Gareth J. Jenkins; Shareen H. Doak; Martin J. D. Clift. 2019. "Cellular Defense Mechanisms Following Nanomaterial Exposure: A Focus on Oxidative Stress and Cytotoxicity." 2D Nanoelectronics , no. : 243-254.
Introduction: The expanding use of multiwalled carbon nanotubes (MWCNTs) in various consumer and industrial products has raised concerns regarding the potential health risks following the inhalation of this nanomaterial. Recent studies indicate that MWCNT exposure can cause deleterious lung effects. Pulmonary fibrosis is one of the diseases associated with the inhalation of classical fiber-shaped materials (e.g., asbestos), and recently MWCNTs.Materials and Methods: Herein, the presented work investigated early signs of fibrosis in key human lung cell types implicated directly (fibroblasts) or indirectly (alveolar epithelial cells and macrophages) in the pathogenesis of lung fibrosis, upon acute (24 hours) and prolonged (96 hours) exposure to different concentrations (5–20 μg/mL) of long, rigid Mitsui-7 MWCNTs. These results were compared to those inflicted upon the same cell types following exposure to tangled nanofibers, that is, Nanocyl-7000, and a positive particle control, crystalline quartz (i.e., Min-U-Sil).Results: Mitsui-7 interacted with all cell types tested, in particular, single nanotubes were readily internalized by each cell type. Exposure to Mitsui-7 resulted in a proinflammatory response in macrophages at 24 hours (interleukin-1β release). However, only prolonged Mitsui-7 exposure induced a significant release of profibrotic mediators (transforming growth factor-β, platelet derived-growth factor, and osteopontin) in all tested cell cultures and concentrations, highlighting the importance of prolonged exposure studies in nanosafety assessment. This elevated release of profibrotic markers was not accompanied by an increased collagen production or cell proliferation in fibroblasts in the tested time frame.Conclusion: Overall, prolonged exposure to human-relevant CNT concentrations appears to be a highly suitable approach to predict profibrotic response in vitro.
Savvina Chortarea; Fikad Zerimariam; Hana Barosova; Dedy Septiadi; Martin J.D. Clift; Alke Fink; Barbara Rothen-Rutishauser. Profibrotic Activity of Multiwalled Carbon Nanotubes Upon Prolonged Exposures in Different Human Lung Cell Types. Applied In Vitro Toxicology 2019, 5, 47 -61.
AMA StyleSavvina Chortarea, Fikad Zerimariam, Hana Barosova, Dedy Septiadi, Martin J.D. Clift, Alke Fink, Barbara Rothen-Rutishauser. Profibrotic Activity of Multiwalled Carbon Nanotubes Upon Prolonged Exposures in Different Human Lung Cell Types. Applied In Vitro Toxicology. 2019; 5 (1):47-61.
Chicago/Turabian StyleSavvina Chortarea; Fikad Zerimariam; Hana Barosova; Dedy Septiadi; Martin J.D. Clift; Alke Fink; Barbara Rothen-Rutishauser. 2019. "Profibrotic Activity of Multiwalled Carbon Nanotubes Upon Prolonged Exposures in Different Human Lung Cell Types." Applied In Vitro Toxicology 5, no. 1: 47-61.
It is well established that toxicological evaluation of engineered nanomaterials (NMs) is vital to ensure the health and safety of those exposed to them. Further, there is a distinct need for the development of advanced physiologically relevant in vitro techniques for NM hazard prediction due to the limited predictive power of current in vitro models and the unsustainability of conducting nano-safety evaluations in vivo. Thus, the purpose of this study was to develop alternative in vitro approaches to assess the potential of NMs to induce genotoxicity by secondary mechanisms. This was first undertaken by a conditioned media-based technique, whereby cell culture media was transferred from differentiated THP-1 (dTHP-1) macrophages treated with γ-Fe2O3 or Fe3O4 superparamagnetic iron oxide nanoparticles (SPIONs) to the bronchial cell line 16HBE14o−. Secondly construction and SPION treatment of a co-culture model comprising of 16HBE14o− cells and dTHP-1 macrophages. For both of these approaches no cytotoxicity was detected and chromosomal damage was evaluated by the in vitro micronucleus assay. Genotoxicity assessment was also performed using 16HBE14o− monocultures, which demonstrated only γ-Fe2O3 nanoparticles to be capable of inducing chromosomal damage. In contrast, immune cell conditioned media and dual cell co-culture SPION treatments showed both SPION types to be genotoxic to 16HBE14o− cells due to secondary genotoxicity promoted by SPION-immune cell interaction. The findings of the present study demonstrate that the approach of using single in vitro cell test systems precludes the ability to consider secondary genotoxic mechanisms. Consequently, the use of multi-cell type models is preferable as they better mimic the in vivo environment and thus offer the potential to enhance understanding and detection of a wider breadth of potential damage induced by NMs.
Stephen J. Evans; Martin J. D. Clift; Neenu Singh; John W. Wills; Nicole Hondow; Thomas S. Wilkinson; Michael J. Burgum; Andy P. Brown; Gareth J. Jenkins; Shareen H. Doak. In vitro detection of in vitro secondary mechanisms of genotoxicity induced by engineered nanomaterials. Particle and Fibre Toxicology 2019, 16, 1 -14.
AMA StyleStephen J. Evans, Martin J. D. Clift, Neenu Singh, John W. Wills, Nicole Hondow, Thomas S. Wilkinson, Michael J. Burgum, Andy P. Brown, Gareth J. Jenkins, Shareen H. Doak. In vitro detection of in vitro secondary mechanisms of genotoxicity induced by engineered nanomaterials. Particle and Fibre Toxicology. 2019; 16 (1):1-14.
Chicago/Turabian StyleStephen J. Evans; Martin J. D. Clift; Neenu Singh; John W. Wills; Nicole Hondow; Thomas S. Wilkinson; Michael J. Burgum; Andy P. Brown; Gareth J. Jenkins; Shareen H. Doak. 2019. "In vitro detection of in vitro secondary mechanisms of genotoxicity induced by engineered nanomaterials." Particle and Fibre Toxicology 16, no. 1: 1-14.
Marta Alonso-Nocelo; Ramon Alvarez-Puebla; Tomás Bauleth-Ramos; Mattias Björnmalm; Belén López Bouzo; Michael J. Burgum; Semih Calamak; Gizem Calibasi Kocal; Ai-Zheng Chen; Ciro Chiappini; Martin J.D. Clift; Ana F. Cruz; Daxiang Cui; Jiwei Cui; María De La Fuente; Utkan Demirci; Shareen H. Doak; Naside G. Durmus; Menekse Ermis; Stephen J. Evans; Kelong Fan; Michelle E. Farkas; Patrícia Figueiredo; Nuno A. Fonseca; Ana C. Gregório; Luca Guerrini; Sinan Guven; Kimberly Hamad-Schifferli; Jingcheng Hao; Joseph Hardie; Tayyaba Hasan; Nesrin Hasirci; Vasif Hasirci; Ting He; Jouni Hirvonen; Chih-Chia Huang; Yan Huang; Peng Huang; ShuaiDong Huo; Roshni Iyer; Gareth J. Jenkins; Ying Jiang; Ranjith K. Kankala; Chien-Wei Lee; Yue Li; Fan Li; Xing-Jie Liang; Eliana M. Lima; Jing Lin; Tzu-Ming Liu; Gang Liu; Rui M. Lopes; Davide A. Martella; Livia P. Mendes; João Nuno Moreira; Vera Moura; Kytai T. Nguyen; Mary Okesola; Dona Padanilam; Adriele Prina-Mello; Eduardo G. Rico; Imran Rizvi; Cristina Rodriguez-Quijada; Vincent M. Rotello; Juan Ruiz-Bañobre; Hélder A. Santos; Bruno Sarmento; Sérgio Simões; Tuanwei Sun; Vladimir P. Torchilin; Ângela Valério-Fernandes; Abi Judit Vázquez-Ríos; Shi-Bin Wang; Yu-Chi Wang; Ling Wang; Zhe Wang; Junqing Wang; Joseph Wolf; Xiyun Yan; Yu S. Zhang; Daria Zhukova. Contributors. Handbook of Nanomaterials for Cancer Theranostics 2018, 1 .
AMA StyleMarta Alonso-Nocelo, Ramon Alvarez-Puebla, Tomás Bauleth-Ramos, Mattias Björnmalm, Belén López Bouzo, Michael J. Burgum, Semih Calamak, Gizem Calibasi Kocal, Ai-Zheng Chen, Ciro Chiappini, Martin J.D. Clift, Ana F. Cruz, Daxiang Cui, Jiwei Cui, María De La Fuente, Utkan Demirci, Shareen H. Doak, Naside G. Durmus, Menekse Ermis, Stephen J. Evans, Kelong Fan, Michelle E. Farkas, Patrícia Figueiredo, Nuno A. Fonseca, Ana C. Gregório, Luca Guerrini, Sinan Guven, Kimberly Hamad-Schifferli, Jingcheng Hao, Joseph Hardie, Tayyaba Hasan, Nesrin Hasirci, Vasif Hasirci, Ting He, Jouni Hirvonen, Chih-Chia Huang, Yan Huang, Peng Huang, ShuaiDong Huo, Roshni Iyer, Gareth J. Jenkins, Ying Jiang, Ranjith K. Kankala, Chien-Wei Lee, Yue Li, Fan Li, Xing-Jie Liang, Eliana M. Lima, Jing Lin, Tzu-Ming Liu, Gang Liu, Rui M. Lopes, Davide A. Martella, Livia P. Mendes, João Nuno Moreira, Vera Moura, Kytai T. Nguyen, Mary Okesola, Dona Padanilam, Adriele Prina-Mello, Eduardo G. Rico, Imran Rizvi, Cristina Rodriguez-Quijada, Vincent M. Rotello, Juan Ruiz-Bañobre, Hélder A. Santos, Bruno Sarmento, Sérgio Simões, Tuanwei Sun, Vladimir P. Torchilin, Ângela Valério-Fernandes, Abi Judit Vázquez-Ríos, Shi-Bin Wang, Yu-Chi Wang, Ling Wang, Zhe Wang, Junqing Wang, Joseph Wolf, Xiyun Yan, Yu S. Zhang, Daria Zhukova. Contributors. Handbook of Nanomaterials for Cancer Theranostics. 2018; ():1.
Chicago/Turabian StyleMarta Alonso-Nocelo; Ramon Alvarez-Puebla; Tomás Bauleth-Ramos; Mattias Björnmalm; Belén López Bouzo; Michael J. Burgum; Semih Calamak; Gizem Calibasi Kocal; Ai-Zheng Chen; Ciro Chiappini; Martin J.D. Clift; Ana F. Cruz; Daxiang Cui; Jiwei Cui; María De La Fuente; Utkan Demirci; Shareen H. Doak; Naside G. Durmus; Menekse Ermis; Stephen J. Evans; Kelong Fan; Michelle E. Farkas; Patrícia Figueiredo; Nuno A. Fonseca; Ana C. Gregório; Luca Guerrini; Sinan Guven; Kimberly Hamad-Schifferli; Jingcheng Hao; Joseph Hardie; Tayyaba Hasan; Nesrin Hasirci; Vasif Hasirci; Ting He; Jouni Hirvonen; Chih-Chia Huang; Yan Huang; Peng Huang; ShuaiDong Huo; Roshni Iyer; Gareth J. Jenkins; Ying Jiang; Ranjith K. Kankala; Chien-Wei Lee; Yue Li; Fan Li; Xing-Jie Liang; Eliana M. Lima; Jing Lin; Tzu-Ming Liu; Gang Liu; Rui M. Lopes; Davide A. Martella; Livia P. Mendes; João Nuno Moreira; Vera Moura; Kytai T. Nguyen; Mary Okesola; Dona Padanilam; Adriele Prina-Mello; Eduardo G. Rico; Imran Rizvi; Cristina Rodriguez-Quijada; Vincent M. Rotello; Juan Ruiz-Bañobre; Hélder A. Santos; Bruno Sarmento; Sérgio Simões; Tuanwei Sun; Vladimir P. Torchilin; Ângela Valério-Fernandes; Abi Judit Vázquez-Ríos; Shi-Bin Wang; Yu-Chi Wang; Ling Wang; Zhe Wang; Junqing Wang; Joseph Wolf; Xiyun Yan; Yu S. Zhang; Daria Zhukova. 2018. "Contributors." Handbook of Nanomaterials for Cancer Theranostics , no. : 1.
The research field of nanotechnology promises to deliver copious advantages to the scientific, technological, and industrial divisions, globally. Most notable, and in focus in this chapter, is the contribution of nanotechnology to the medical sector where engineered nanoparticles (ENPs) and nanomaterials (ENMs) can be beneficially applied to monitor, diagnose, and potentially treat human health. Despite heightened interest from industrial and consumer markets pertaining to the significant advantages proposed through ENM medical applications. There remains a substantial concern as to the adverse environmental and human health implications of novel ENMs, particularly within nanomedicine, the clinical application of nanotechnology. Nanotheranostics, now an established science concerned with diagnosing and treating specific adverse human health conditions, utilizes a host of novel ENMs. Initially these ENMs require extensive physicochemical characterization coupled with far-reaching biologically relevant testing encompassing complex in vitro (co-culture) cell models, in vivo and human trials before clinical approval and ultimate use. This chapter will provide an overview of the considerations as to the biocompatibility and toxicological impact of novel nanotheranostics building upon the foundation of metal and carbon-based ENMs as well as quantum dots (QDs) which hold tremendous potential owing to their extremely small size and biological marker capabilities.
Michael J. Burgum; Stephen J. Evans; Gareth J. Jenkins; Shareen H. Doak; Martin J.D. Clift. Considerations for the Human Health Implications of Nanotheranostics. Handbook of Nanomaterials for Cancer Theranostics 2018, 279 -303.
AMA StyleMichael J. Burgum, Stephen J. Evans, Gareth J. Jenkins, Shareen H. Doak, Martin J.D. Clift. Considerations for the Human Health Implications of Nanotheranostics. Handbook of Nanomaterials for Cancer Theranostics. 2018; ():279-303.
Chicago/Turabian StyleMichael J. Burgum; Stephen J. Evans; Gareth J. Jenkins; Shareen H. Doak; Martin J.D. Clift. 2018. "Considerations for the Human Health Implications of Nanotheranostics." Handbook of Nanomaterials for Cancer Theranostics , no. : 279-303.
Communities resident in urban areas located near active volcanoes can experience volcanic ash exposures during, and following, an eruption, in addition to sustained exposures to high concentrations of anthropogenic air pollutants (e.g., vehicle exhaust emissions). Inhalation of anthropogenic pollution is known to cause the onset of, or exacerbate, respiratory and cardiovascular diseases. It is further postulated similar exposure to volcanic ash can also affect such disease states. Understanding of the impact of combined exposure of volcanic ash and anthropogenic pollution to human health, however, remains limited. The aim of this study was to assess the biological impact of combined exposure to respirable volcanic ash (from Soufrière Hills volcano (SHV), Montserrat and Chaitén volcano (ChV), Chile; representing different magmatic compositions and eruption styles) and freshly-generated complete exhaust from a gasoline vehicle. A multicellular human lung model (an epithelial cell-layer composed of A549 alveolar type II-like cells complemented with human blood monocyte-derived macrophages and dendritic cells cultured at the air-liquid interface) was exposed to diluted exhaust (1:10) continuously for 6 h, followed by immediate exposure to the ash as a dry powder (0.54 ± 0.19 μg/cm2 and 0.39 ± 0.09 μg/cm2 for SHV and ChV ash, respectively). After an 18 h incubation, cells were exposed again for 6 h to diluted exhaust, and a final 18 h incubation (at 37 °C and 5% CO2). Cell cultures were then assessed for cytotoxic, oxidative stress and (pro-)inflammatory responses. Results indicate that, at all tested (sub-lethal) concentrations, co-exposures with both ash samples induced no significant expression of genes associated with oxidative stress (HMOX1, NQO1) or production of (pro-)inflammatory markers (IL-1β, IL-8, TNF-α) at the gene and protein levels. In summary, considering the employed experimental conditions, combined exposure of volcanic ash and gasoline vehicle exhaust has a limited short-term biological impact to an advanced lung cell in vitro model.
Ines Tomašek; Claire J. Horwell; Christoph Bisig; David E. Damby; Pierre Comte; Jan Czerwinski; Alke Petri-Fink; Martin J.D. Clift; Barbara Drasler; Barbara Rothen-Rutishauser. Respiratory hazard assessment of combined exposure to complete gasoline exhaust and respirable volcanic ash in a multicellular human lung model at the air-liquid interface. Environmental Pollution 2018, 238, 977 -987.
AMA StyleInes Tomašek, Claire J. Horwell, Christoph Bisig, David E. Damby, Pierre Comte, Jan Czerwinski, Alke Petri-Fink, Martin J.D. Clift, Barbara Drasler, Barbara Rothen-Rutishauser. Respiratory hazard assessment of combined exposure to complete gasoline exhaust and respirable volcanic ash in a multicellular human lung model at the air-liquid interface. Environmental Pollution. 2018; 238 ():977-987.
Chicago/Turabian StyleInes Tomašek; Claire J. Horwell; Christoph Bisig; David E. Damby; Pierre Comte; Jan Czerwinski; Alke Petri-Fink; Martin J.D. Clift; Barbara Drasler; Barbara Rothen-Rutishauser. 2018. "Respiratory hazard assessment of combined exposure to complete gasoline exhaust and respirable volcanic ash in a multicellular human lung model at the air-liquid interface." Environmental Pollution 238, no. : 977-987.
Wear particles from automotive friction brake pads of various sizes, morphology, and chemical composition are significant contributors towards particulate matter. Knowledge concerning the potential adverse effects following inhalation exposure to brake wear debris is limited. Our aim was, therefore, to generate brake wear particles released from commercial low-metallic and non-asbestos organic automotive brake pads used in mid-size passenger cars by a full-scale brake dynamometer with an environmental chamber simulating urban driving and to deduce their potential hazard in vitro. The collected fractions were analysed using scanning electron microscopy via energy-dispersive X-ray spectroscopy (SEM–EDS) and Raman microspectroscopy. The biological impact of the samples was investigated using a human 3D multicellular model consisting of human epithelial cells (A549) and human primary immune cells (macrophages and dendritic cells) mimicking the human epithelial tissue barrier. The viability, morphology, oxidative stress, and (pro-)inflammatory response of the cells were assessed following 24 h exposure to ~ 12, ~ 24, and ~ 48 µg/cm2 of non-airborne samples and to ~ 3.7 µg/cm2 of different brake wear size fractions (2–4, 1–2, and 0.25–1 µm) applying a pseudo-air–liquid interface approach. Brake wear debris with low-metallic formula does not induce any adverse biological effects to the in vitro lung multicellular model. Brake wear particles from non-asbestos organic formulated pads, however, induced increased (pro-)inflammatory mediator release from the same in vitro system. The latter finding can be attributed to the different particle compositions, specifically the presence of anatase.
Hana Barosova; Savvina Chortarea; Pavlina Peikertova; Martin J. D. Clift; Alke Petri-Fink; Jana Kukutschova; Barbara Rothen-Rutishauser. Biological response of an in vitro human 3D lung cell model exposed to brake wear debris varies based on brake pad formulation. Archives of Toxicology 2018, 92, 2339 -2351.
AMA StyleHana Barosova, Savvina Chortarea, Pavlina Peikertova, Martin J. D. Clift, Alke Petri-Fink, Jana Kukutschova, Barbara Rothen-Rutishauser. Biological response of an in vitro human 3D lung cell model exposed to brake wear debris varies based on brake pad formulation. Archives of Toxicology. 2018; 92 (7):2339-2351.
Chicago/Turabian StyleHana Barosova; Savvina Chortarea; Pavlina Peikertova; Martin J. D. Clift; Alke Petri-Fink; Jana Kukutschova; Barbara Rothen-Rutishauser. 2018. "Biological response of an in vitro human 3D lung cell model exposed to brake wear debris varies based on brake pad formulation." Archives of Toxicology 92, no. 7: 2339-2351.
Reliable characterization of cellulose nanomaterials is critical for their utilization in various applications.
E. Johan Foster; Robert J. Moon; Umesh P. Agarwal; Michael J. Bortner; Julien Bras; Sandra Camarero-Espinosa; Kathleen J. Chan; Martin J. D. Clift; Emily D. Cranston; Stephen J. Eichhorn; Douglas M. Fox; Wadood Y. Hamad; Laurent Heux; Bruno Jean; Matthew Korey; World Nieh; Kimberly J. Ong; Michael S. Reid; Scott Renneckar; Rose Roberts; Jo Anne Shatkin; John Simonsen; Kelly Stinson-Bagby; Nandula Wanasekara; Jeffrey Youngblood. Current characterization methods for cellulose nanomaterials. Chemical Society Reviews 2018, 47, 2609 -2679.
AMA StyleE. Johan Foster, Robert J. Moon, Umesh P. Agarwal, Michael J. Bortner, Julien Bras, Sandra Camarero-Espinosa, Kathleen J. Chan, Martin J. D. Clift, Emily D. Cranston, Stephen J. Eichhorn, Douglas M. Fox, Wadood Y. Hamad, Laurent Heux, Bruno Jean, Matthew Korey, World Nieh, Kimberly J. Ong, Michael S. Reid, Scott Renneckar, Rose Roberts, Jo Anne Shatkin, John Simonsen, Kelly Stinson-Bagby, Nandula Wanasekara, Jeffrey Youngblood. Current characterization methods for cellulose nanomaterials. Chemical Society Reviews. 2018; 47 (8):2609-2679.
Chicago/Turabian StyleE. Johan Foster; Robert J. Moon; Umesh P. Agarwal; Michael J. Bortner; Julien Bras; Sandra Camarero-Espinosa; Kathleen J. Chan; Martin J. D. Clift; Emily D. Cranston; Stephen J. Eichhorn; Douglas M. Fox; Wadood Y. Hamad; Laurent Heux; Bruno Jean; Matthew Korey; World Nieh; Kimberly J. Ong; Michael S. Reid; Scott Renneckar; Rose Roberts; Jo Anne Shatkin; John Simonsen; Kelly Stinson-Bagby; Nandula Wanasekara; Jeffrey Youngblood. 2018. "Current characterization methods for cellulose nanomaterials." Chemical Society Reviews 47, no. 8: 2609-2679.
Nanomaterials convey numerous advantages, and the past decade has seen a considerable rise in their development and production for an expanse of applications. While the potential advantages of nanomaterials are clear, concerns over the impact of human and environmental exposure exist. Concerted, science-led efforts are required to understand the effects of nanomaterial exposure and ensure that protection goals are met. There is much on-going discussion regarding how best to assess nanomaterial risk, particularly considering the large number of tests that may be required. A plethora of forms may need to be tested for each nanomaterial, and risk assessed throughout the life cycle, meaning numerous acute and chronic toxicity studies could be required, which is neither practical nor utilises the current evidence-base. Hence, there are scientific, business, ethical and legislative drivers to re-consider the use of animal toxicity tests. An expert Working Group of regulators, academics and industry scientists were gathered by the UK's NC3Rs to discuss: i) opportunities being offered in the short, medium and long-terms to advance nanosafety, ii) how to align these advances with the application of the 3Rs in nanomaterial safety testing, and iii) shifting the focus of risk assessment from current hazard-based approaches towards exposure-driven approaches.
Natalie Burden; Karin Aschberger; Qasim Chaudhry; Martin J.D. Clift; Paul Fowler; Helinor Johnston; Robert Landsiedel; Joanna Rowland; Vicki Stone; Shareen H. Doak. Aligning nanotoxicology with the 3Rs: What is needed to realise the short, medium and long-term opportunities? Regulatory Toxicology and Pharmacology 2017, 91, 257 -266.
AMA StyleNatalie Burden, Karin Aschberger, Qasim Chaudhry, Martin J.D. Clift, Paul Fowler, Helinor Johnston, Robert Landsiedel, Joanna Rowland, Vicki Stone, Shareen H. Doak. Aligning nanotoxicology with the 3Rs: What is needed to realise the short, medium and long-term opportunities? Regulatory Toxicology and Pharmacology. 2017; 91 ():257-266.
Chicago/Turabian StyleNatalie Burden; Karin Aschberger; Qasim Chaudhry; Martin J.D. Clift; Paul Fowler; Helinor Johnston; Robert Landsiedel; Joanna Rowland; Vicki Stone; Shareen H. Doak. 2017. "Aligning nanotoxicology with the 3Rs: What is needed to realise the short, medium and long-term opportunities?" Regulatory Toxicology and Pharmacology 91, no. : 257-266.
Ali Kermanizadeh; Kim Jantzen; Astrid Skovmand; Ana C. D. Gouveia; Nicklas R. Jacobsen; Vicki Stone; Martin J. D. Clift. Overview of the Current Knowledge and Challenges Associated with Human Exposure to Nanomaterials. Biocatalysis and Nanotechnology 2017, 775 -809.
AMA StyleAli Kermanizadeh, Kim Jantzen, Astrid Skovmand, Ana C. D. Gouveia, Nicklas R. Jacobsen, Vicki Stone, Martin J. D. Clift. Overview of the Current Knowledge and Challenges Associated with Human Exposure to Nanomaterials. Biocatalysis and Nanotechnology. 2017; ():775-809.
Chicago/Turabian StyleAli Kermanizadeh; Kim Jantzen; Astrid Skovmand; Ana C. D. Gouveia; Nicklas R. Jacobsen; Vicki Stone; Martin J. D. Clift. 2017. "Overview of the Current Knowledge and Challenges Associated with Human Exposure to Nanomaterials." Biocatalysis and Nanotechnology , no. : 775-809.