Preliminary Toxicological Analysis in a Safe-by-Design and Adverse Outcome Pathway-Driven Approach on Different Silver Nanoparticles: Assessment of Acute Responses in A549 Cells

Silver nanoparticles (Ag NPs) are among the most widely used metal-based nanomaterials (NMs) and their applications in different products, also as antibacterial additives, are increasing. In the present manuscript, according to an adverse outcome pathway (AOP) approach, we tested two safe-by-design (SbD) newly developed Ag NPs coated with hydroxyethyl cellulose (HEC), namely AgHEC powder and AgHEC solution. These novel Ag NPs were compared to two reference Ag NPs (naked and coated with polyvinylpyrrolidone—PVP). Cell viability, inflammatory response, reactive oxygen species, oxidative DNA damage, cell cycle, and cell–particle interactions were analyzed in the alveolar in vitro model, A549 cells. The results show a different toxicity pattern of the novel Ag NPs compared to reference NPs and that between the two novel NPs, the AgHEC solution is the one with the lower toxicity and to be further developed within the SbD framework.

[1]  Yiru Niu,et al.  In vitro review of nanoparticles attacking macrophages: Interaction and cell death. , 2022, Life sciences.

[2]  S. Parapini,et al.  Eco design for Ag-based solutions against SARS-CoV-2 and E. coli , 2022, Environmental Science: Nano.

[3]  M. Eskandani,et al.  Recent advances in γH2AX biomarker-based genotoxicity assays: A marker of DNA damage and repair. , 2021, DNA repair.

[4]  Arandi Ginane Bezerra Junior,et al.  Toxicological effects of silver nanoparticles and cadmium chloride in macrophage cell line (RAW 264.7): An in vitro approach. , 2021, Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements.

[5]  F. Cassee,et al.  Safe by design (SbD) and nanotechnology: a much-discussed topic with a prudence? , 2021, Particle and fibre toxicology.

[6]  M. Garcés,et al.  Current understanding of nanoparticle toxicity mechanisms and interactions with biological systems , 2021, New Journal of Chemistry.

[7]  Nelson Caro,et al.  Silver Nanoparticles and Their Antibacterial Applications , 2021, International journal of molecular sciences.

[8]  M. Peana,et al.  An updated overview on metal nanoparticles toxicity. , 2021, Seminars in cancer biology.

[9]  S. Nabavi,et al.  Reactive oxygen species modulators in pulmonary medicine. , 2021, Current opinion in pharmacology.

[10]  T. Douki,et al.  Toxicity and chemical transformation of silver nanoparticles in A549 lung cells: dose-rate-dependent genotoxic impact , 2021, Environmental Science: Nano.

[11]  E. Demir.  A review on nanotoxicity and nanogenotoxicity of different shapes of nanomaterials , 2020, Journal of applied toxicology : JAT.

[12]  J. Boratýnski,et al.  Hydroxyethylcellulose as a methotrexate carrier in anticancer therapy , 2020, Investigational New Drugs.

[13]  U. Vogel,et al.  Adverse outcome pathways as a tool for the design of testing strategies to support the safety assessment of emerging advanced materials at the nanoscale , 2020, Particle and Fibre Toxicology.

[14]  L. Delgado-Roche,et al.  Oxidative Stress as Key Player in Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) Infection , 2020, Archives of Medical Research.

[15]  Manfred Zinn,et al.  A Methodological Safe-by-Design Approach for the Development of Nanomedicines , 2020, Frontiers in Bioengineering and Biotechnology.

[16]  Nicholas K. Geitner,et al.  Caveats to the use of MTT, neutral red, Hoechst and Resazurin to measure silver nanoparticle cytotoxicity. , 2020, Chemico-biological interactions.

[17]  N. Durán,et al.  Silver nanoparticles: Toxicity in model organisms as an overview of its hazard for human health and the environment. , 2019, Journal of hazardous materials.

[18]  M. Selman,et al.  The leading role of epithelial cells in the pathogenesis of idiopathic pulmonary fibrosis. , 2019, Cellular signalling.

[19]  M. Bottone,et al.  Pulmonary and hepatic effects after low dose exposure to nanosilver: Early and long-lasting histological and ultrastructural alterations in rat , 2019, Toxicology reports.

[20]  M. Blosi,et al.  Innovative synthesis of nanostructured composite materials by a spray-freeze drying process: Efficient catalysts and photocatalysts preparation , 2019, Catalysis Today.

[21]  A. Pugazhendhi,et al.  Synthesis of Silver Nanoparticles and their Biomedical Applications - A Comprehensive Review. , 2019, Current pharmaceutical design.

[22]  A. Khademhosseini,et al.  Recent advances in nanoengineering cellulose for cargo delivery. , 2019, Journal of controlled release : official journal of the Controlled Release Society.

[23]  E. Rahimpour,et al.  Effect of silver nanoparticles in the induction of apoptosis on human hepatocellular carcinoma (HepG2) cell line. , 2018, Materials science & engineering. C, Materials for biological applications.

[24]  S. Gurunathan,et al.  Nanoparticle-Mediated Combination Therapy: Two-in-One Approach for Cancer , 2018, International journal of molecular sciences.

[25]  H. Griffiths,et al.  The dual role of Reactive Oxygen Species in autoimmune and inflammatory diseases: evidence from preclinical models , 2018, Free radical biology & medicine.

[26]  Alexandru Mihai Grumezescu,et al.  Biomedical Applications of Silver Nanoparticles: An Up-to-Date Overview , 2018, Nanomaterials.

[27]  D. Gardini,et al.  Nanosilver: An innovative paradigm to promote its safe and active use , 2018, NanoImpact.

[28]  Stephen W. Edwards,et al.  The Adverse Outcome Pathway: A Multifaceted Framework Supporting 21st Century Toxicology. , 2018, Current opinion in toxicology.

[29]  Adriele Prina-Mello,et al.  Silver nanoparticles as a medical device in healthcare settings: a five-step approach for candidate screening of coating agents , 2018, Royal Society Open Science.

[30]  Valeria De Matteis,et al.  Toxicity Assessment in the Nanoparticle Era. , 2018, Advances in experimental medicine and biology.

[31]  S. H. Bennekou,et al.  Adverse outcome pathways: opportunities, limitations and open questions , 2017, Archives of Toxicology.

[32]  A. T. Ogunjimi,et al.  Evaluation of distribution, redox parameters, and genotoxicity in Wistar rats co-exposed to silver and titanium dioxide nanoparticles , 2017, Journal of toxicology and environmental health. Part A.

[33]  Hayelom Dargo Beyene,et al.  Synthesis paradigm and applications of silver nanoparticles (AgNPs), a review , 2017, Sustainable Materials and Technologies.

[34]  V. Castranova,et al.  Role of epithelial‐mesenchymal transition (EMT) and fibroblast function in cerium oxide nanoparticles‐induced lung fibrosis , 2017, Toxicology and applied pharmacology.

[35]  Sharon Munn,et al.  The Adverse Outcome Pathway approach in nanotoxicology , 2017 .

[36]  Lei Dong,et al.  Specifically Formed Corona on Silica Nanoparticles Enhances Transforming Growth Factor β1 Activity in Triggering Lung Fibrosis. , 2017, ACS nano.

[37]  Anne Gourmelon,et al.  The Adverse Outcome Pathway Concept: A Basis for Developing Regulatory Decision-making Tools , 2016, Alternatives to laboratory animals : ATLA.

[38]  Xiaoxu Zhao,et al.  Coexposure to silver nanoparticles and ultraviolet A synergistically enhances the phosphorylation of histone H2AX. , 2016, Journal of photochemistry and photobiology. B, Biology.

[39]  Y. Hashimoto,et al.  A Review of Silver Nanoparticles: Synthesis Methods, Properties and Applications , 2015 .

[40]  J. Ravanat,et al.  Stress-induced DNA damage biomarkers: applications and limitations , 2015, Front. Chem..

[41]  Meiying Wang,et al.  NADPH Oxidase-Dependent NLRP3 Inflammasome Activation and its Important Role in Lung Fibrosis by Multiwalled Carbon Nanotubes. , 2015, Small.

[42]  S. Gurunathan,et al.  Oxidative stress mediated cytotoxicity of biologically synthesized silver nanoparticles in human lung epithelial adenocarcinoma cell line , 2014, Nanoscale Research Letters.

[43]  V. Kähäri,et al.  Matrix metalloproteinases in inflammation. , 2014, Biochimica et biophysica acta.

[44]  M. Camatini,et al.  Nickel oxide nanoparticles induce inflammation and genotoxic effect in lung epithelial cells. , 2014, Toxicology letters.

[45]  R Core Team,et al.  R: A language and environment for statistical computing. , 2014 .

[46]  M. Camatini,et al.  The modality of cell-particle interactions drives the toxicity of nanosized CuO and TiO₂ in human alveolar epithelial cells. , 2013, Toxicology letters.

[47]  H. Simon,et al.  Living and dying for inflammation: neutrophils, eosinophils, basophils. , 2013, Trends in immunology.

[48]  M. Teixeira,et al.  Resolution of inflammation: mechanisms and opportunity for drug development. , 2013, Pharmacology & therapeutics.

[49]  Bernd Nowack,et al.  120 years of nanosilver history: implications for policy makers. , 2011, Environmental science & technology.

[50]  Holger Moch,et al.  Nanoparticle cytotoxicity depends on intracellular solubility: comparison of stabilized copper metal and degradable copper oxide nanoparticles. , 2010, Toxicology letters.

[51]  V. Vishwakarma,et al.  Safety and Risk Associated with Nanoparticles - A Review , 2010 .

[52]  K. Hensley,et al.  Inhalation of environmental stressors & chronic inflammation: autoimmunity and neurodegeneration. , 2009, Mutation research.

[53]  P. Beard,et al.  H2AX Is Required for Cell Cycle Arrest via the p53/p21 Pathway , 2009, Molecular and Cellular Biology.

[54]  Naomi Lubick,et al.  Nanosilver toxicity: ions, nanoparticles--or both? , 2008, Environmental science & technology.

[55]  Z. Darżynkiewicz,et al.  ATM activation accompanies histone H2AX phosphorylation in A549 cells upon exposure to tobacco smoke , 2007, BMC Cell Biology.

[56]  V. Castranova.  Signaling pathways controlling the production of inflammatory mediators in response to crystalline silica exposure: role of reactive oxygen/nitrogen species. , 2004, Free radical biology & medicine.

[57]  Tzu-Hao Wang,et al.  Detection and treatment of mycoplasma contamination in cultured cells. , 2003, Chang Gung medical journal.