Welcome to the BIORIMA Forum!
BIORIMA is developing an Integrated Risk Management Framework for Nano-BioMaterials used in medical devices and advanced therapeutic medicinal products. This forum is a discussion platform, where you, as an end-user or stakeholder, can directly engage with the project, exchange and share your views and ideas with our experts, or just give us your feedback on issues relevant for your business and work. How to use this forum: To send a post on the BIORIMA forum, you will need to register first by using the menu link “Register” below on the right. Once your registration is confirmed, you can click on one of the topics below and then post your feedback, comment or question directly by using the NEWTOPIC button. If you have any issues, please email Lesley Tobin: Lesleytobin@hotmail.com.
Bengt Fadeel a; Christoph Alexiou b a Nanomedicine & Nanosafety Laboratory (NNL), Division of Molecular Toxicology, Institute of Environmental Medicine, Karolinska Institutet, 171 77, Stockholm, Sweden b Department of Oto-Rhino-Laryngology, Head and Neck Surgery, Section for Experimental Oncology and Nanomedicine (SEON), University Hospital Erlangen, Else Kröner-Fresenius-Stiftung Professorship, 91054, Erlangen, Germany
Nanomedicine is at a crossroads: with relatively few success stories in terms of clinical translation despite more and more research on increasingly sophisticated nanomaterials, it is important to consider whether we are on the right track. Indeed, it is crucial that we address the fact that while considerable efforts are being made to overcome barriers to translation from the bench to the clinic, scientists are still struggling to decipher fundamental aspects of nanomaterial interactions with biological systems. We believe that a key to the successful adoption of nanomedicines in oncology and beyond lies in a deeper understanding of underlying biological processes and in decoding interactions between engineered nanomaterials and biological systems. Here we provide an overview of progress in nanomedicine during the past 5 years.
Arianna Marucco 1, Marion Prono 2, David Beal 2, Enrica Alasonati 3, Paola Fisicaro 3,Enrico Bergamaschi 4, Marie Carriere 2,*and Ivana Fenoglio 1,* 1 Department of Chemistry, University of Torino, 10125 Torino, Italy; firstname.lastname@example.org 2 Chimie Interface Biologie pour l’Environnement, la Santéet la Toxicologie (CIBEST),University Grenoble Alpes, CEA, CNRS, IRIG, SyMMES, F-38000 Grenoble, France;email@example.com (M.P.); firstname.lastname@example.org (D.B.) 3 Département Biomédicale et Chimie Inorganique, Laboratoire National de Métrologie et D’essais,F-75724 Paris, France; Enrica.Alasonati@lne.fr (E.A.); Paola.Fisicaro@lne.fr (P.F.) 4 Department of Public Health and Pediatrics, University of Torino, 10126 Torino, Italy;email@example.com*Correspondence: firstname.lastname@example.org (M.C.); email@example.com (I.F.)
Abstract: Background: Oral exposure to titanium dioxide (TiO2) is common since it is widely used in ood and pharmaceutical products. Concern on the safety of this substance has been recently raised, due to the presence of an ultrafine fraction in food-grade TiO2. Discrepancy exists among data reported in in vitro and in vivo studies on intestinal acute/chronic toxicity of TiO2. This might be due to the different biological identity of TiO2 in traditional in vitro test by respect in vivo conditions.
by Elisa Giubilato1 [OrcID] , Virginia Cazzagon1 [OrcID] , Mónica J. B. Amorim 2 [OrcID] , Magda Blosi 3, Jacques Bouillard 4, Hans Bouwmeester 5 [OrcID] , Anna Luisa Costa 3 [OrcID] , Bengt Fadeel 6, Teresa F. Fernandes 7, Carlos Fito 8 [OrcID] , Marina Hauser 9, Antonio Marcomini 1, Bernd Nowack 9 [OrcID] , Lisa Pizzol 10 [OrcID] , Leagh Powell 11, Adriele Prina-Mello 12 [OrcID] , Haralambos Sarimveis 13, Janeck James Scott-Fordsmand 14, Elena Semenzin 1 [OrcID] , Burkhard Stahlmecke 15 [OrcID] , Vicki Stone 11 OrcID] , Alexis Vignes 4 [OrcID] , Terry Wilkins 16, Alex Zabeo 10, Lang Tran 17 and Danail Hristozov 1,* 1 Department of Environmental Sciences, Informatics and Statistics, University Ca’ Foscari of Venice, Via Torino 155, 30172 Venice, Italy 2 Department of Biology and CESAM, University of Aveiro, 3810-193 Aveiro, Portugal 3 Institute of Science and Technology for Ceramics, National Research Council of Italy (CNR-ISTEC), Via Granarolo 64, 48018 Faenza, Italy 4 Institut National de l’Environnement industriel et des Risques, Parc Technologique ALATA, 60550 Verneuil-en-Halatte, France 5 Division of Toxicology, Wageningen University, 6708 WE Wageningen, The Netherlands 6 Division of Molecular Toxicology, Institute of Environmental Medicine, Karolinska Institutet, 171 77 Stockholm, Sweden 7 Institute of Life and Earth Sciences, School of Energy, Geoscience, Infrastructure and Society, Heriot-Watt University, Edinburgh EH14 4AS, UK 8 Instituto Tecnologico del Embalaje, Transporte y Logistica, 46980 Paterna-Valencia, Spain 9 Empa, Swiss Federal Laboratories for Materials Science and Technology, Lerchenfeldstrasse 5, 9014 St. Gallen, Switzerland 10 GreenDecision Srl, Via delle Industrie, 21/8, 30175 Venice, Italy 11 Institute of Biological Chemistry, Biophysics and Bioengineering, School of Engineering and Physical Sciences, Heriot-Watt University, Edinburgh EH14 4AS, UK 12 Trinity Translational Medicine Institute, Trinity College, The University of Dublin, Dublin 8, Ireland 13 School of Chemical Engineering, National Technical University of Athens, 15780 Athens, Greece 14 Department of Bioscience, Aarhus University, 8600 Silkeborg, Denmark 15 Institut für Energie und Umwelttechnik e.V., 47229 Duisburg, Germany 16 Nanomanufacturing Institute, School of Chemical and Process Engineering, University of Leeds, Leeds LS2 9JT, UK 17 Institute of Occupational Medicine, Research Avenue North, Riccarton, Edinburgh EH14 4AP, UK * Author to whom correspondence should be addressed. Materials 2020, 13(20), 4532; https://doi.org/10.3390/ma13204532
Abstract The convergence of nanotechnology and biotechnology has led to substantial advancements in nano-biomaterials (NBMs) used in medical devices (MD) and advanced therapy medicinal products (ATMP). However, there are concerns that applications of NBMs for medical diagnostics, therapeutics and regenerative medicine could also pose health and/or environmental risks since the current understanding of their safety is incomplete. A scientific strategy is therefore needed to assess all risks emerging along the life cycles of these products. To address this need, an overarching risk management framework (RMF) for NBMs used in MD and ATMP is presented in this paper, as a result of a collaborative effort of a team of experts within the EU Project BIORIMA and with relevant inputs from external stakeholders. The framework, in line with current regulatory requirements, is designed according to state-of-the-art approaches to risk assessment and management of both nanomaterials and biomaterials. The collection/generation of data for NBMs safety assessment is based on innovative integrated approaches to testing and assessment (IATA). The framework can support stakeholders (e.g., manufacturers, regulators, consultants) in systematically assessing not only patient safety but also occupational (including healthcare workers) and environmental risks along the life cycle of MD and ATMP. The outputs of the framework enable the user to identify suitable safe(r)-by-design alternatives and/or risk management measures and to compare the risks of NBMs to their (clinical) benefits, based on efficacy, quality and cost criteria, in order to inform robust risk management decision-making.
Evidence supports the advantages of inhalation over other drug-administration routes in the treatment of lung diseases, including cancer. Although data obtained from animal models and conventional in vitro cultures are informative, testing the efficacy of inhaled chemotherapeutic agents requires human-relevant preclinical tools. Such tools are currently unavailable. Here, we developed and characterized in vitro models for the efficacy testing of inhaled chemotherapeutic agents against non-small-cell lung cancer (NSCLC). These models recapitulated key elements of both the lung epithelium and the tumour tissue, namely the direct contact with the gas phase and the three-dimensional (3D) architecture. Our in vitro models were formed by growing, for the first time, human adenocarcinoma (A549) cells as multilayered mono-cultures at the Air-Liquid Interface (ALI). The in vitro models were tested for their response to four benchmarking chemotherapeutics, currently in use in clinics, demonstrating an increased resistance to these drugs as compared to sub-confluent monolayered 2D cell cultures. Chemoresistance was comparable to that detected in 3D hypoxic tumour spheroids. Being cultured in ALI conditions, the multilayered monocultures demonstrated to be compatible with testing drugs administered as a liquid aerosol by a clinical nebulizer, offering an advantage over 3D tumour spheroids. In conclusion, we demonstrated that our in vitro models provide new human-relevant tools allowing for the efficacy screening of inhaled anti-cancer drugs.
Georgia Wilson Jones, Marco P Monopoli, Luisa Campagnolo, Antonio Pietroiusti, Lang Tran & Bengt Fadeel
There is an urgent need for safe and effective approaches to combat COVID-19. Here, we asked whether lessons learned from nanotoxicology and nanomedicine could shed light on the current pandemic. SARS-CoV-2, the causative agent, may trigger a mild, self-limiting disease with respiratory symptoms, but patients may also succumb to a life-threatening systemic disease. The host response to the virus is equally complex and studies are now beginning to unravel the immunological correlates of COVID-19. Nanotechnology can be applied for the delivery of antiviral drugs or other repurposed drugs. Moreover, recent work has shown that synthetic nanoparticles wrapped with host-derived cellular membranes may prevent virus infection. We posit that nanoparticles decorated with ACE2, the receptor for SARS-CoV-2, could be exploited as decoys to intercept the virus before it infects cells in the respiratory tract. However, close attention should be paid to biocompatibility before such nano-decoys are deployed in the clinic.
MarinaHauserBerndNowack Empa, Swiss Federal Laboratories for Materials Science and Technology, Lerchenfeldstrasse 5, 9014 St. Gallen, Switzerland
Nanobiomaterials (NBMs) are currently being tested in numerous biomedical applications, and their use is expected to grow rapidly in the near future. Many different types of nanomaterials are employed for a wide variety of different applications. Silver nanoparticles (nano-Ag) have been investigated for their antibacterial, antifungal, and osteoinductive properties to be used in catheters, wound healing, dental applications, and bone healing. Polymeric nanoparticles such as poly(lactic-co-glycolic acid) (PLGA) are mainly studied for their ability to deliver cancer drugs as the body metabolizes them into simple compounds. However, most of these applications are still in the development stage and unavailable on the market, meaning that information on possible consumption, material flows, and concentrations in the environment is lacking. We thus modeled a realistic scenario involving several nano-Ag and PLGA applications which are already in use or likely to reach the market soon. We assumed their full market penetration in Europe in order to explore the prospective flows of NBMs and their environmental concentrations. The potential flows of three application-specific composite materials were also examined for one precise application each: Fe3O4PEG-PLGA used in drug delivery, MgHA-collagen used for bone tissue engineering, and PLLA-Ag applied in wound healing. Mean annual consumption in Europe, considering all realistic and probable applications of the respective NBMs, was estimated to be 5,650 kg of nano-Ag and 48,000 kg of PLGA. Mean annual consumption of the three application-specific materials under the full market penetration scenario was estimated to be 4,000 kg of Fe3O4PEG-PLGA, 58 kg of MgHA-collagen, and 24,300 kg of PLLA-Ag. A probabilistic material-flow model was used to quantify flows of the NBMs studied from production, through use, and on to end-of-life in the environment. The highest possible worst-case predicted environmental concentration (wc-PEC) were found to occur in sewage sludge, with 0.2 µg/kg of nano-Ag, 400 µg/kg of PLGA, 33 µg/kg of Fe3O4PEG-PLGA, 0.007 µg/kg of MgHA-collagen, and 2.9 µg/kg of PLLA-Ag. PLGA exhibited the highest concentration in all environmental compartments except natural and urban soil, where nano-Ag showed the highest concentration. The results showed that the distribution of NBMs into different environmental and technical compartments is strongly dependent on their type of application.
Dania Movia 1 , Solene Bruni-Favier 1 , Adriele Prina-Mello 1 2 1 Laboratory for Biological Characterisation of Advanced Materials (LBCAM), Department of Clinical Medicine, Trinity Translational Medicine Institute, Trinity College, The University of Dublin, Dublin, Ireland. 2 AMBER Centre, CRANN Institute, Trinity College, The University of Dublin, Dublin, Ireland. PMID: 32582672 PMCID: PMC7284111 DOI: 10.3389/fbioe.2020.00549
When assessing the risk and hazard of a non-pharmaceutical compound, the first step is determining acute toxicity, including toxicity following inhalation. Inhalation is a major exposure route for humans, and the respiratory epithelium is the first tissue that inhaled substances directly interact with. Acute inhalation toxicity testing for regulatory purposes is currently performed only in rats and/or mice according to OECD TG403, TG436, and TG433 test guidelines. Such tests are biased by the differences in the respiratory tract architecture and function across species, making it difficult to draw conclusions on the potential hazard of inhaled compounds in humans. Research efforts have been therefore focused on developing alternative, human-relevant models, with emphasis on the creation of advanced In vitro models. To date, there is no In vitro model that has been accepted by regulatory agencies as a stand-alone replacement for inhalation toxicity testing in animals. Here, we provide a brief introduction to current OECD test guidelines for acute inhalation toxicity, the interspecies differences affecting the predictive value of such tests, and the current regulatory efforts to advance alternative approaches to animal-based inhalation toxicity studies. We then list the steps that should allow overcoming the current challenges in validating In vitro alternatives for the successful replacement of animal-based inhalation toxicity studies. These steps are inclusive and descriptive, and should be detailed when adopting in house-produced 3D cell models for inhalation tests. Hence, we provide a checklist of key parameters that should be reported in any future scientific publications for reproducibility and transparency.
M. J. B. Amorim, M. L. Fernández-Cruz, K. Hund-Rinke & J. J. Scott-Fordsmand Environmental Sciences Europe volume 32, Article number: 101 (2020)
The European Medicines Agency (EMA) regards the potential risks of human medicinal products to the environment and their impacts are assessed, as well as management to limit this impact. Hazard assessment of novel materials, which differ from conventional chemicals, e.g. nanobiomaterials, poses testing challenges and represents a work-in-progress with much focus on the optimization of required methodologies. For this work-in-progress, we here highlight where changes/updates are required in relation to the main elements for international testing based on OECD guidelines, supported by knowledge from the nanotoxicity area. The outline describes two major sections, nanobiomaterials and environmental hazards, including its challenges and learned lessons, with recommendations for implementation in OECD guidelines. Finally, the way forward via a testing strategy is described.
Bengt Fadeel* Nanosafety and Nanomedicine Laboratory, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden
George Whitesides remarked, in his excellent perspective on the “right” size in nanobiotechnology, that “there already exists a highly developed science concerned with biologically relevant nanostructures: this science is called chemistry” (Whitesides, 2003). To this, one may add that there also exists a scientific discipline dealing with host responses to foreign objects on the nano- and microscale—it is called immunology (Shvedova et al., 2010). Whitesides goes on to explain that “biology also provides unparalleled examples of functional nanostructures to excite the imagination of nanotechnologists of all persuasions” (Whitesides, 2003). Indeed, as pointed out by Bruce Alberts in another visionary perspective, “the entire cell can be viewed as a factory that contains an elaborate network of interlocking assembly lines, each of which is composed of a set of large protein machines” (Alberts, 1998). These protein “machines” are oftentimes of nanoscale dimensions (van den Heuvel and Dekker, 2007).
Nanomedicine holds tremendous promise, yet despite the huge number of basic and preclinical studies, few nanomedicines have reached the clinic (Chan, 2017). Perhaps we have underestimated the complexity of biological systems, and that of human disease? Perhaps, as pointed out in a recent review, we need to view organs and cells in the body as complicit in the actions of nanomedicines: the chemistry of a material is altered upon contact with a biological system, and these changes determine its fate and function in the body (Chan, 2017). The reciprocal nature of so-called nano-bio interactions could be exploited for therapeutic gain if the underlying mechanisms are understood. However, the same features that may prove useful in the context of a disease may also turn out to be involved in the unwanted effects of a nanomaterial; toxicology and medicine may, in some respects, be viewed as two sides of the same coin.
Marianna I. Kotzabasaki, ORCID logo *a Iason Sotiropoulos ORCID logo a and Haralambos Sarimveis ORCID logo *a Author affiliations * Corresponding authors a School of Chemical Engineering, National Technical University of Athens, 9 Heroon Polytechneiou Street, Zografou Campus, Athens, Greece E-mail: firstname.lastname@example.org, email@example.com, firstname.lastname@example.org Fax: +302107723138 Tel: +302107723236 Abstract
The use of in silico approaches for the prediction of biomedical properties of nano-biomaterials (NBMs) can play a significant role in guiding and reducing wetlab experiments. Computational methods, such as data mining and machine learning techniques, can increase the efficiency and reduce the time and cost required for hazard and risk assesment and for designing new safer NBMs. A major obstacle in developing accurate and well-validated in silico models such as Nano Quantitative Structure–Activity Relationships (Nano-QSARs) is that although the volume of data published in the literature is increasing, the data are fragmented in many different publications and are not sufficiently curated for modelling purposes. Moreover, NBMs exhibit high complexity and heterogeneity in their structures, making data collection and curation and QSAR model development more challenging compared to traditional small molecules. The aim of this study was to construct and fully validate a Nano-QSAR model for the prediction of toxicological properties of superparamagnetic iron oxide nanoparticles (SPIONs), focusing on their application as Magnetic Resonance Imaging (MRI) contrast agents for non-invasive stem cell labelling and tracking. To achieve this goal, we first performed an extensive search through the literature for collecting and curating relevant data and we developed a dataset containing both physicochemical and toxicological properties of SPIONs. The data were analysed next, using Automated machine learning (Auto-ML) approaches for optimising the development and validation of nanotoxicity classification QSAR models of SPIONs. Further analysis of relative attribute importances revealed that physicochemical properties such as the size and the magnetic core are the dominant attributes correlated to the toxicity of SPIONs. Our results suggest that as more systematic information from NBM experimental tests becomes available, computational tools could play an important role in supporting the safety-by-design (SbD) concept in regenerative medicine and disease therapeutics.
Dania Movia, Despina Bazou & Adriele Prina-Mello BMC Cancer volume 19, Article number: 854 (2019) Cite this article
Abstract Background Lung cancer is the leading cause of cancer-related deaths worldwide. This study focuses on its most common form, Non-Small-Cell Lung Cancer (NSCLC). No cure exists for advanced NSCLC, and patient prognosis is extremely poor. Efforts are currently being made to develop effective inhaled NSCLC therapies. However, at present, reliable preclinical models to support the development of inhaled anti-cancer drugs do not exist. This is due to the oversimplified nature of currently available in vitro models, and the significant interspecies differences between animals and humans.
1Dania Movia*, 2,3 Maroua Benhaddada, 2Jolanda Spadavecchia, 1,4Adriele Prina-Mello*1 LBCAM, Department of Clinical Medicine, Trinity Translational Medicine Institute, Trinity College Dublin, Dublin, Ireland 2 CNRS, UMR 7244, NBD-CSPBAT, Laboratoire de Chimie, Structures et Propriétés de Biomatériaux et d’Agents Thérapeutiques Université Sorbonne Paris Nord, Bobigny, France 3 TORSKAL nanoscience, Sainte Clotilde, La Réuinon, France 4 AMBER Centre, CRANN Institute, Trinity College Dublin, Dublin, Ireland
Keywords Gold nanoparticle 1 ; external stimuli; physical stimuli; physically triggered nanomedicine. Quote this article as: Movia D, Benhaddada M, Jolanda Spadavecchia J, Prina - Mello A, Latest advances in combining gold nanomaterials with physical stimuli towards new responsive therapeutic and diagnostic strategies, Precis. Nanomed. 2020 Apr il;3(2):495 - 524 , https://doi.org/ 10.33218/001c.12650 Abstract Nanomedicine aims at enhancing treatment efficiency and/or improving diagnostic sensitivity by better controlling several critical parameters, such as tissue targeting and off target toxicity. More recently, advanced nanomedicine products have been developed to achieve spatially and temporally controlled therapy and diagnosis. This review focuses on gold nanomaterials (AuNMs) and alloy/hybrid AuNMs that can be used in stimuli-responsive strategies for therapeutic and diagnostic applications. Endogenous and/or exogenous stimuli can be used as a trigger for such systems. Herein, we focus on those activated by exogenous stimuli. Our review starts from one specific externally activated product, Aurolase®, which recently underwent clinical studies. Further we continue describing a specific physically triggered category, for which the exogeneous stimulus applied induces a structural transformation or modification that is essential for their therapeutic and/or diagnostic action. Gold nanomaterials are grouped both by the nature of the function they exert (therapeutic or diagnostic) and the stimuli class.
Full paper available here: https://precisionnanomedicine.com/articl...stic-strategies Corresponding authors: Email: email@example.com; firstname.lastname@example.org; Full postal address: Lab 0.74, Trinity Translational Medicine Institute, Trinity Centre for Health Sciences, James’s Street, D8, Dublin, Ireland.
Abstract Length and aspect ratio represent important toxicity determinants of fibrous nanomaterials. We have previously shown that anatase TiO2nanofibers (TiO2 NF) cause a dose-dependent decrease of cell viability as well as the loss of epithelial barrier integrity in polarized airway cell monolayers. Herein we have investigated the impact of fiber shortening, obtained by ball-milling, on the biological effects of TiO2 NF. Long TiO2NF (L-TiO2 NF) were more cytotoxic than their shortened counterparts (S-TiO2 NF) towards alveolar A549 cells and bronchial 16HBE cells. Moreover, L-TiO2 NF affected the trans-epithelial electrical resistance of 16HBE monolayers. This effect was associated with altered distribution of tight-junction proteins and also mitigated by fiber shortening. Macrophages efficiently internalized S-TiO2 NF but not L-TiO2 NF, which caused cell stretching and deformation. In macrophages S-TiO2 NF enhanced the expression of pro-inflammatory genes, NO production and cytokine secretion, which was significantly inhibited by the phagocytosis inhibitor cytochalasin D. In vivo experiments indicated length-dependent toxicity in both the lungs and peritoneal cavity of mice, leading to significant increase in markers of inflammation in animals treated with L-TiO2 NF. It is concluded that fiber shortening mitigates NF detrimental effects on cell viability and epithelial barrier competence. As far as inflammation is concerned, shortening enhances phagocytosis and macrophage activation in vitro but prevents the increase of inflammatory cytokines upon in vivo exposure. These data suggest that fiber shortening may represent an effective safe-by-design strategy for mitigating TiO2 NF toxic effects both in vitro and in vivo.
Massimiliano G.Bianchi 1 Ovidio Bussolati 1 Martina Chiu 1 GiuseppeTaurino 1 Enrico Bergamasch i2 1 Laboratory of General Pathology, Department of Medicine and Surgery, University of Parma, Parma, Italy 2 Department of Public Health Science and Pediatrics, University of Turin, Turin, Italy
A growing number of engineered nanomaterials (ENMs) are produced and marketed. Increasing human exposure is, therefore, expected in the next years and, in parallel, increased concerns on potential health impact will be raised with particular reference to workers engaged in ENM production, handling, or disposal. Moreover, ENMs are also present in products widely present on the market, such as food additives or cosmetics, so that potential effects on human health could involve a larger population. However, until now, no adverse health effect in humans has been clearly demonstrated to be ENM-specific. Although the huge amount of data on ENM biological effects, obtained using in vitro models and experimental animals, cannot be used to demonstrate ENM-related adverse outcomes in humans, they have produced valuable information on the complex and dynamic interactions between ENM and living systems. At the light of these developments, lack of documented health effects should not be taken as an absolute evidence of absence of ENM-related risks, but, rather, as a powerful drive to increase research efforts toward a robust preventive evaluation of ENM potential toxicity before their entry the market.
P. Weyell,a H.-D. Kurland,b T. Hülser,c J. Grabow,b F. A. Müllerb and D. Kralisch ORCID logo *a Author affiliations
* Corresponding authors
a Friedrich Schiller University Jena, Pharmaceutical Technology and Biopharmacy, Lessingstraße 8, 07743 Jena, Germany E-mail: email@example.com Fax: +49 3641 949942 Tel: +49 3641 949951
b Friedrich Schiller University Jena, Otto Schott Institute of Materials Research (OSIM), Löbdergraben 32, 07743 Jena, Germany
c Institut für Energie- und Umwelttechnik e.V. (IUTA), Bliersheimer Straße 58-60, 47229 Duisburg, Germany Abstract
Laser vaporisation is a promising technology for the industrial manufacturing of spherical, oxidic nanoparticles, including crystalline, less-agglomerated ferromagnetic maghemite (γ-Fe2O3) and superparamagnetic γ-Fe2O3/amorphous SiO2 composite nanoparticles. These can be utilised in medical applications such as contrast agents in magnetic resonance imaging (MRI) and may replace common contrast agents such as gadolinium chelate complexes. Nano-specific risk assessment and life cycle assessment have been used in parallel in order to critically assess benefits and shortcomings of this technological approach and to find the key parameters for process optimisation. Potential risks in occupational safety were found to be low, but the energy demand of the laser system is crucial in terms of environmental impact potential. However, process optimisation options in process efficiency, laser source and reuse of waste heat were identified, leading to a decrease of the overall cumulated energy demand up to 94%. Flame spray pyrolysis was included in the comparative study as an alternative approach for gas phase synthesis of oxidic nanoparticles. Both technologies and the resulting nanoenabled products were found to be environmentally beneficial compared to the preparation of the standard MRI contrast agent Gadovist®.
Monique C. P. Mendonça 1,2,*,†, Natália P. Rodrigues 2,†, Marcelo B. de Jesus 1 [OrcID] and Mónica J. B. Amorim 2,* [OrcID] 1Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas, Campinas, São Paulo 13083-970, Brazil 2Department of Biology, CESAM, University of Aveiro, Aveiro 3810-193, Portugal *Authors to whom correspondence should be addressed. †These authors contributed equally to this work.
Abstract Graphene-based nanomaterials (GBNs) possess unique physicochemical properties, allowing a wide range of applications in physical, chemical, and biomedical fields. Although GBNs are broadly used, information about their adverse effects on ecosystem health, especially in the terrestrial environment, is limited. Therefore, this study aims to assess the toxicity of two commonly used derivatives of GBNs, graphene oxide (GO) and reduced graphene oxide (rGO), in the soil invertebrate Enchytraeus crypticus using a reduced full life cycle test. At higher exposure concentrations, GO induced high mortality and severe impairment in the reproduction rate, while rGO showed little adverse effect up to 1000 mg/kg. Collectively, our body of results suggests that the degree of oxidation of GO correlates with their toxic effects on E. crypticus, which argues against generalization on GBNs ecotoxicity. Identifying the key factors affecting the toxicity of GBNs, including ecotoxicity, is urgent for the design of safe GBNs for commercial purposes.
Marina Hauser and Bernd Nowack* Empa, Swiss Federal Laboratories for Materials Science and Technology, St. Gallen, Switzerland
The growth in development and use of nanobiomaterials (NBMs) has raised questions regarding their possible distribution in the environment. Because most NBMs are not yet available on the market and exposure monitoring is thus not possible, prospective exposure modeling is the method of choice to get information on their future environmental exposure. An important input for such models is the fraction of the NBM excreted after their application to humans. The aim of this study was to analyze the current literature on excretion of NBMs using a meta-analysis. Published pharmacokinetic data from in vivo animal experiments was collected and compiled in a database, including information on the material characteristics. An evaluation of the data showed that there is no correlation between the excretion (in % of injected dose, ID) and the material type, the dose, the zeta potential or the size of the particles. However, the excretion is dependent on the type of administration with orally administered NBMs being excreted to a larger extent than intravenously administered ones. A statistically significant difference was found for IV vs. oral and oral vs. inhalation. The database provided by this work can be used for future studies to parameterize the transfer of NBMs from humans to wastewater. Generic probability distributions of excretion for oral and IV-administration are provided to enable excretion modeling of NBMs without data for a specific NBM.
Abstract Inorganic materials are receiving significant interest in medicine given their usefulness for therapeutic applications such as targeted drug delivery, carriers of active pharmaceutical and medical imaging. However, the poor knowledge of the side effects related to their use is an obstacle to their clinical translation. For the molecular drug development, safe-by-design has become as a novel pharmaceutical strategy that allows a reduction of the costs and an acceleration of the translation of research to market. In the case of materials, the application of such approaches is hampered by a poor knowledge of how the physical and chemical properties of the material trigger biological response. Hemocompatibility is a crucial factor for those materials that are intended for medical applications. In particular, the formation of agglomerates is a serious side effect that may induce occlusion of blood vessels and thrombotic events. Additionally, nanoparticles can interfere with the coagulation cascades where they have been reported to induce both pro- and anti-coagulant properties where their properties like size, shape and surface charge have been see to be critical parameters. Here, we developed two sets of tailored carbon and silica nano/submicron-particles with three different sizes (100-500 nm) with the purpose of investigating the role of surface curvature and chemistry on platelet aggregation, activation and adhesion. We show that that large carbon nanoparticles, but not small carbon nanoparticles or silica nanoparticles, have a strong tendency to form aggregates both in plasma and blood, as a consequence of the formation of a protein corona and not of platelets activation. Substantial differences were found in the composition of the protein corona depending upon the chemical nature of the nanoparticles, while the surface curvature plays a minor role. On the other hand, coagulation proteins were abundant in the corona of both silica and carbon nanoparticles. The results presented herein suggest that vessel occlusion and formation of thrombi in vivo may occur through independent mode of action (MoA), differently affected by the physico-chemical properties of the materials.
Monique C.P.Mendonça ab1 Natália P.Rodrigues b1 Janeck J.Scott-Fordsmand c Marcelo Bispo de Jesus a Mónica J.B.Amorim b aDepartment of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas, Campinas, São Paulo, 13083-970, Brazil bDepartment of Biology, CESAM, University of Aveiro, Aveiro, 3810-193, Portugal cDepartment of Bioscience, Aarhus University, Silkeborg, DK-8600, Denmark
Abstract The widespread production and use of silver nanomaterials (AgNMs) in consumer and medical products have been raising environmental concerns. Once in the environment, the soil is one of the major sinks of AgNMs due to e.g. sewage sludge applications, and invertebrates are directly exposed. In this study, we investigate the potential of N-acetylcysteine (NAC) to reduce the toxic effects of Ag NM300 K (and AgNO3) on the soil invertebrate Enchytraeus crypticus. Ag NM300 K induces mortality, reproduction impairment, and avoidance. The addition of NAC to the soil showed a remarkable reduction in the toxicity of Ag, indicating that NAC can act as a detoxifying agent for terrestrial organisms exposed to Ag materials. That the reduction in toxicity likely is caused by thiol groups, was confirmed by GSH and GSSH studies. Identifying the mechanisms and hence alternatives that allow the recovery of contaminated soils is an important mitigation measure to promote environmental safety and reduce the associated risks to human health. Further, it may inform on strategies to implement in safe-by-design industry development.
Sandeep Keshavan, Paolo Calligari, Lorenzo Stella, Laura Fusco, Lucia Gemma Delogu & Bengt Fadeel Cell Death & Disease volume 10, Article number: 569 (2019)
Abstract Neutrophils are key components of the innate arm of the immune system and represent the frontline of host defense against intruding pathogens. However, neutrophils can also cause damage to the host. Nanomaterials are being developed for a multitude of different purposes and these minute materials may find their way into the body through deliberate or inadvertent exposure; understanding nanomaterial interactions with the immune system is therefore of critical importance. However, whereas numerous studies have focused on macrophages, less attention is devoted to nanomaterial interactions with neutrophils, the most abundant leukocytes in the blood. We discuss the impact of engineered nanomaterials on neutrophils and how neutrophils, in turn, may digest certain carbon-based materials such as carbon nanotubes and graphene oxide. We also discuss the role of the corona of proteins adsorbed onto the surface of nanomaterials and whether nanomaterials are sensed as pathogens by cells of the immune system.