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Takáč P, Michalková R, Čižmáriková M, Bedlovičová Z, Balážová Ľ, Laca Megyesi Š, Mačeková Z, Takáčová G, Moreno-Borrallo A, Ruiz-Hernandez E, Isakov L, Takáč P. Do We Know Enough About the Safety Profile of Silver Nanoparticles in Oncology? A Focus on Novel Methods and Approaches. Int J Mol Sci 2025; 26:5344. [PMID: 40508153 PMCID: PMC12155435 DOI: 10.3390/ijms26115344] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2025] [Revised: 05/22/2025] [Accepted: 05/28/2025] [Indexed: 06/16/2025] Open
Abstract
Silver nanoparticles (AgNPs) have emerged as promising agents in cancer diagnostics and/or therapy, demonstrating a lot of possible pharmacological actions. However, understanding the pharmacokinetics and safety profiles of nanoparticles, which is crucial for their clinical application, still raises many questions. Studies indicate that AgNPs can accumulate in tumour tissues, improving drug delivery and specificity. However, their interaction with biological systems necessitates thorough safety evaluations. Classical methods for assessing AgNPs' safety include cytotoxicity assays, genotoxicity tests, and histopathological examinations. However, novel techniques are emerging, such as advanced imaging and biomarker analysis, offering more precise toxicity assessments. Prediction models, including computational simulations and in silico analyses, are being developed to forecast AgNPs' toxicity profiles. These models aim to reduce reliance on animal testing and expedite the evaluation process. To mitigate potential risks associated with nanoparticle-based therapies, strategies such as surface modification, controlled release systems, and targeted delivery are being explored. These methods aim to enhance therapeutic efficacy while minimizing adverse effects. The main aim of this review article is to describe AgNPs from the point of view of their pharmacokinetic/toxicokinetic profile in the light of modern knowledge. Special attention will be given to novel methods for assessing the safety and toxicity profiles of AgNPs, providing insights into their interactions with cancer therapies and their potential clinical applications.
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Affiliation(s)
- Peter Takáč
- Department of Pharmacology and Toxicology, University of Veterinary Medicine and Pharmacy in Košice, Komenského 73, 041 81 Košice, Slovakia
| | - Radka Michalková
- Department of Pharmacology, Faculty of Medicine, Pavol Jozef Šafárik University, 040 01 Košice, Slovakia
| | - Martina Čižmáriková
- Department of Pharmacology, Faculty of Medicine, Pavol Jozef Šafárik University, 040 01 Košice, Slovakia
| | - Zdenka Bedlovičová
- Department of Chemistry, Biochemistry and Biophysics, University of Veterinary Medicine and Pharmacy in Košice, Komenského 73, 041 81 Košice, Slovakia
| | - Ľudmila Balážová
- Department of Pharmaceutical Technology, Pharmacognosy and Botany, University of Veterinary Medicine and Pharmacy in Košice, 041 81 Košice, Slovakia
| | - Štefánia Laca Megyesi
- Department of Pharmacy and Social Pharmacy, University of Veterinary Medicine and Pharmacy in Košice, 041 81 Košice, Slovakia
| | - Zuzana Mačeková
- Department of Pharmacy and Social Pharmacy, University of Veterinary Medicine and Pharmacy in Košice, 041 81 Košice, Slovakia
| | - Gabriela Takáčová
- Department of Dermatovenerology, Faculty of Medicine, Pavol Jozef Šafárik University and L. Pasteur University Hospital in Košice, 040 01 Košice, Slovakia
| | - Almudena Moreno-Borrallo
- School of Pharmacy and Pharmaceutical Sciences, Trinity College Dublin, D02 YY50 Dublin, Ireland
| | - Eduardo Ruiz-Hernandez
- School of Pharmacy and Pharmaceutical Sciences, Trinity College Dublin, D02 YY50 Dublin, Ireland
| | - Luka Isakov
- BioSense Institute, University of Novi Sad, Dr. Zorana Đinđića 1, 21102 Novi Sad, Serbia
| | - Peter Takáč
- Department of Physical Medicine, Balneology and Medical Rehabilitation, Faculty of Medicine, Pavol Jozef Šafárik University and L. Pasteur University Hospital in Košice, 040 01 Košice, Slovakia
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Zacchini M. Bismuth interaction with plants: Uptake and transport, toxic effects, tolerance mechanisms - A review. CHEMOSPHERE 2024; 360:142414. [PMID: 38789054 DOI: 10.1016/j.chemosphere.2024.142414] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/04/2024] [Revised: 05/02/2024] [Accepted: 05/22/2024] [Indexed: 05/26/2024]
Abstract
Bismuth (Bi) is a minor metal whose abundance on Earth is estimated at 0.025 ppm. Known since ancient times for its medical properties, its use in many industrial applications has increased significantly in recent years due to its physical and chemical properties. Considered less toxic than other metals, Bi has been defined as a "green metal" and has been suggested as a replacement for lead in many industrial processes. Although the occurrence of Bi in the environment is predicted to increase, there is still a lack of information on its interaction with biota. Even though it is absorbed by many organisms, Bi has not been directly implicated in the regulation of fundamental metabolic processes. This review summarises the fragmentary knowledge on the interaction between Bi and plants. Toxic effects at the growth, physiological and biochemical levels have been described in Bi-treated plants, with varying degrees and consequences for plant vitality, mostly depending on the chemical formulation of Bi, the concentration of Bi, the growth medium, the time of exposure, and the experimental conditions (laboratory or outdoor conditions). Bismuth has been shown to be readily absorbed and translocated in plants, interfering with plant growth and development, photosynthetic processes, nutrient uptake and accumulation, and metal (especially iron) homeostasis. Like other metals, Bi can induce an oxidative stress state in plant cells, and genotoxic effects have been reported in Bi-treated plants. Tolerance responses to the excess presence of Bi have been poorly described and are mostly referred to as the activation of antioxidant defences involving enzymatic and non-enzymatic molecules. The goal of this review is to offer an overview of the present knowledge on the interaction of Bi and plants, highlighting the gaps to be filled to better understand the role of Bi in affecting key physiological processes in plants. This will help to assess the potential harm of this metal in the environment, where its occurrence is predicted to increase due to the growing demand for medicinal and industrial applications.
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Affiliation(s)
- Massimo Zacchini
- Research Institute on Terrestrial Ecosystems (IRET), National Research Council of Italy (CNR), Via Salaria Km 29.300, 00015, Monterotondo Scalo Roma, Italy; NBFC, National Biodiversity Future Center S.c.a.r.l., Piazza Marina 61 (c/o Palazzo Steri), 90133, Palermo, Italy.
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Grzesiakowska A, Kasprowicz MJ, Kuchta-Gładysz M, Rymuza K, Szeleszczuk O. Genotoxicity of physical silver nanoparticles, produced by the HVAD method, for Chinchilla lanigera genome. Sci Rep 2021; 11:18473. [PMID: 34531461 PMCID: PMC8446028 DOI: 10.1038/s41598-021-97926-9] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2021] [Accepted: 09/01/2021] [Indexed: 12/12/2022] Open
Abstract
Each year, growing demand for silver nanoparticles (AgNP) contributes to the search for alternative methods of their production. Stable AgNP with antibacterial properties, low toxicity to the environment and living organisms are especially valued. In the study presented here, an attempt was made to assess the toxicity of two AgNP solutions produced using the HVAD method to the Chinchilla lanigera genome. The AgNO3 solution was the indicator and reference for the harmfulness of AgNP. The study was carried out in vitro on bone marrow cells isolated from Chinchilla lanigera bones. The genotoxicity was assessed by comet assay, following the treatment of cells with three silver solutions: unstable and sodium citrate-stabilized silver nanoparticles, as well as silver nitrate at three concentrations (5, 10 and 20 µg/L), after 3, 6 and 24 h. Based on the percentage of the DNA content in the comet tail and the tail moment, an increase in cell DNA integrity disruption was demonstrated in all tested variants: of solution, exposure time and concentration, compared to the control sample. A statistically significant correlation was determined between the level of induced DNA breaks and the concentration of the active solutions and the duration of their activity. A solution of silver nanoparticles stabilized with sodium citrate was shown to have the most harmful effect on bone marrow cells. Silver nitrate demonstrated a level of toxicity similar to these particles. Further studies are necessary to directly compare the genotoxic properties of AgNP produced using the HVAD method and the chemical method under the same conditions.
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Affiliation(s)
- Anna Grzesiakowska
- Department of Animals Reproduction, Anatomy and Genomics, University of Agriculture in Krakow, Mickiewicza Av. 24/28, 30-059, Kraków, Poland.
| | - Marek Jan Kasprowicz
- Department of Soil Science and Agrophysics, University of Agriculture in Krakow, Mickiewicza Av. 21, 31-120, Kraków, Poland
| | - Marta Kuchta-Gładysz
- Department of Animals Reproduction, Anatomy and Genomics, University of Agriculture in Krakow, Mickiewicza Av. 24/28, 30-059, Kraków, Poland.
| | - Katarzyna Rymuza
- Faculty of Agrobioengineering and Animal Husbandry, Siedlce University of Natural Sciences and Humanities, ul. B. Prusa 14, 08-110, Siedlce, Poland
| | - Olga Szeleszczuk
- Department of Animals Reproduction, Anatomy and Genomics, University of Agriculture in Krakow, Mickiewicza Av. 24/28, 30-059, Kraków, Poland
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Cao H, Qin H, Li Y, Jandt KD. The Action-Networks of Nanosilver: Bridging the Gap between Material and Biology. Adv Healthc Mater 2021; 10:e2100619. [PMID: 34309242 PMCID: PMC11468843 DOI: 10.1002/adhm.202100619] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2021] [Revised: 06/03/2021] [Indexed: 01/06/2023]
Abstract
The emergence of nanosilver (silver in nanoscale shapes and their assemblies) benefits the landscape of modern healthcare; however, this brings about concerns over its safety issues associated with an ultrasmall size and high mobility. By reviewing previous reporting details about the synthesis and characterization of nanosilver and its biological responses, a gap between materials synthesis and their biomedical uses is characterized by the insufficient understanding of the interacting and interplaying nanoscale actions of silver. To improve reporting quality and advance clinical translations, it is suggested that researchers have a comprehensive recognition of the "Indications for use" before designing innovative nanosilver-based materials and an "Action-network" concept addressing the acting range and strength of those nanoscale actions is implemented. Although this discussion is specific to nanosilver, the idea of "Indications for use" centered design and synthesis is generally applicable to other biomedical nanomaterials.
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Affiliation(s)
- Huiliang Cao
- Lab of Low‐Dimensional Materials ChemistryKey Laboratory for Ultrafine Materials of Ministry of EducationEast China University of Science and TechnologyShanghai200237China
- Shanghai Engineering Research Center of Hierarchical NanomaterialsSchool of Materials Science and EngineeringEast China University of Science and TechnologyShanghai200237China
- Chair of Materials ScienceOtto Schott Institute of Materials ResearchFriedrich Schiller University JenaJena07743Germany
| | - Hui Qin
- Department of OrthopaedicsShanghai Jiaotong University Affiliated Sixth People's HospitalShanghai200233China
| | - Yongsheng Li
- Lab of Low‐Dimensional Materials ChemistryKey Laboratory for Ultrafine Materials of Ministry of EducationEast China University of Science and TechnologyShanghai200237China
- Shanghai Engineering Research Center of Hierarchical NanomaterialsSchool of Materials Science and EngineeringEast China University of Science and TechnologyShanghai200237China
| | - Klaus D. Jandt
- Chair of Materials ScienceOtto Schott Institute of Materials ResearchFriedrich Schiller University JenaJena07743Germany
- Jena Center for Soft Matter (JCSM)Friedrich Schiller University JenaJena07743Germany
- Jena School for Microbial Communication (JSMC)Neugasse 23Jena07743Germany
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Pourhoseini S, Enos RT, Murphy AE, Cai B, Lead JR. Characterization, bio-uptake and toxicity of polymer-coated silver nanoparticles and their interaction with human peripheral blood mononuclear cells. BEILSTEIN JOURNAL OF NANOTECHNOLOGY 2021; 12:282-294. [PMID: 33842185 PMCID: PMC8008093 DOI: 10.3762/bjnano.12.23] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 09/15/2020] [Accepted: 03/10/2021] [Indexed: 06/12/2023]
Abstract
Silver nanoparticles (AgNPs) are widely used in medical applications due to their antibacterial and antiviral properties. Despite the extensive study of AgNPs, their toxicity and their effect on human health is poorly understood, as a result of issues such as poor control of NP properties and lack of proper characterization. The aim of this study was to investigate the combined characterization, bio-uptake, and toxicity of well-characterized polyvinylpyrrolidone (PVP)-coated AgNPs in exposure media during exposure time using primary human cells (peripheral blood mononuclear cells (PBMCs)). AgNPs were synthesized in-house and characterized using a multimethod approach. Results indicated the transformation of NPs in RPMI medium with a change in size and polydispersity over 24 h of exposure due to dissolution and reprecipitation. No aggregation of NPs was observed in the RPMI medium over the exposure time (24 h). A dose-dependent relationship between PBMC uptake and Ag concentration was detected for both AgNP and AgNO3 treatment. There was approximately a two-fold increase in cellular Ag uptake in the AgNO3 vs the NP treatment. Cytotoxicity, using LDH and MTS assays and based on exposure concentrations was not significantly different when comparing NPs and Ag ions. Based on differential uptake, AgNPs were more toxic after normalizing toxicity to the amount of cellular Ag uptake. Our data highlights the importance of correct synthesis, characterization, and study of transformations to obtain a better understanding of NP uptake and toxicity. Statistical analysis indicated that there might be an individual variability in response to NPs, although more research is required.
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Affiliation(s)
- Sahar Pourhoseini
- Department of Ophthalmology, Baylor College of Medicine, Houston, Texas, 77030, United States
| | - Reilly T Enos
- Department of Pathology, Microbiology, and Immunology, School of Medicine, University of South Carolina, Columbia, SC, 29209, United States
| | - Angela E Murphy
- Department of Pathology, Microbiology, and Immunology, School of Medicine, University of South Carolina, Columbia, SC, 29209, United States
| | - Bo Cai
- Department of Epidemiology and Biostatistics, Arnold School of Public Health, University of South Carolina, Columbia, SC, 29208, United States
| | - Jamie R Lead
- Center for Environmental Nanoscience and Risk, Department of Environmental Health Sciences, Arnold School of Public Health, University of South Carolina, Columbia, SC, 29208, United States
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Kumaravel TS, Brabu B, Parthiban N, Murugan SS, Jha AN. 'Site of contact genotoxicity' assessment for implants - Potential use of single cell gel electrophoresis in biocompatibility testing of medical devices. Toxicol Lett 2021; 341:59-67. [PMID: 33548342 DOI: 10.1016/j.toxlet.2021.01.024] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2020] [Revised: 01/14/2021] [Accepted: 01/30/2021] [Indexed: 11/28/2022]
Abstract
Toxicological risk assessment of medical devices requires genotoxicity assessment as per ISO 10993, Part 3, which is designed to address gene mutations, clastogenicity and/or aneugenicity endpoints. 'Site of contact genotoxicity' is a potential genotoxic risk especially for medical implants, that is currently not addressed in biocompatibility standards. We therefore performed initial validation study on the use of alkaline single cell gel electrophoresis (comet assay) for detecting 'site of contact genotoxicity' of medical devices, using test items made of acrylic implants impregnated with ethyl methanesulphonate (EMS). Comet assay detected increased DNA migration at the site of implantation, but not in the liver. The same implants also failed to show any genotoxicity potentials, when tested on the standard test battery using Salmonella/microsome and chromosome aberration assays. The study suggested that some medical implants can cause 'site of contact genotoxicity', without producing systemic genotoxicity. In conclusion, comet assay will add new dimension to safety assessment of medical devices, and this assay can be added to the battery of genetic toxicology tests for evaluating biocompatibility of medical implants.
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Affiliation(s)
- T S Kumaravel
- GLR Laboratories (Europe) Pvt Ltd, Sharnbrook, MK44 1LZ, United Kingdom; GLR Laboratories Pvt Ltd, Chennai, 600068, India.
| | - B Brabu
- Department of Fiber Science & Apparel Design, College of Human Ecology, Cornell University, Ithaca, NY, 14853, USA
| | - N Parthiban
- GLR Laboratories Pvt Ltd, Chennai, 600068, India
| | - S S Murugan
- GLR Laboratories Pvt Ltd, Chennai, 600068, India
| | - A N Jha
- School of Biological and Marine Sciences, University of Plymouth, Plymouth, PL4 8AA, United Kingdom
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Development and characterization of thin film composite developed from poly (vinyl alcohol) (PVA)/polyethylene glycol (PEG)/norbixin (NBx)/hydroxyapatite. Colloid Polym Sci 2021. [DOI: 10.1007/s00396-020-04777-3] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
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Wang D, Dan M, Ji Y, Wu X, Wang X, Wen H. Roles of ROS and cell cycle arrest in the genotoxicity induced by gold nanorod core/silver shell nanostructure. NANOSCALE RESEARCH LETTERS 2020; 15:224. [PMID: 33284367 PMCID: PMC7721938 DOI: 10.1186/s11671-020-03455-1] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 10/09/2020] [Accepted: 11/27/2020] [Indexed: 06/12/2023]
Abstract
To understand the genotoxicity induced in the liver by silver nanoparticles (AgNPs) and silver ions, an engineered gold nanorod core/silver shell nanostructure (Au@Ag NR) and humanized hepatocyte HepaRG cells were used in this study. The involvement of oxidative stress and cell cycle arrest in the DNA and chromosome damage induced by 0.4-20 µg mL-1 Au@Ag NR were investigated by comet assay, γ-H2AX assay and micronucleus test. Further, the distribution of Au@Ag NR was analyzed. Our results demonstrated that both Ag+ and Au@Ag NR led to DNA cleavage and chromosome damage (clastogenicity) in HepaRG cells and that the Au@Ag NR retained in the nucleus may further release Ag+, aggravating the damages, which are mainly caused by cell cycle arrest and ROS formation. The results reveal the correlation between the intracellular accumulation, Ag+ ion release and the potential genotoxicity of AgNPs.
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Affiliation(s)
- Dan Wang
- Beijing Key Laboratory, National Center for Safety Evaluation of Drugs, National Institutes for Food and Drug Control, Beijing, 100176, People's Republic of China
- China Pharmaceutical University, Nanjing, 211198, People's Republic of China
| | - Mo Dan
- Beijing Key Laboratory, National Center for Safety Evaluation of Drugs, National Institutes for Food and Drug Control, Beijing, 100176, People's Republic of China
- The State Key Laboratory of New Pharmaceutical Preparations and Excipients, 226 Huanghe Road, Shijiazhuang, 050035, Hebei, People's Republic of China
| | - Yinglu Ji
- CAS Key Laboratory of Standardization and Measurement for Nanotechnology and CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing, 100190, People's Republic of China
| | - Xiaochun Wu
- CAS Key Laboratory of Standardization and Measurement for Nanotechnology and CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing, 100190, People's Republic of China.
| | - Xue Wang
- Beijing Key Laboratory, National Center for Safety Evaluation of Drugs, National Institutes for Food and Drug Control, Beijing, 100176, People's Republic of China.
- National Center for Safety Evaluation of Drugs, National Institutes for Food and Drug Control, Key Laboratory of Beijing for Nonclinical Safety Evaluation Research of Drugs, Beijing, 100176, People's Republic of China.
| | - Hairuo Wen
- Beijing Key Laboratory, National Center for Safety Evaluation of Drugs, National Institutes for Food and Drug Control, Beijing, 100176, People's Republic of China.
- National Center for Safety Evaluation of Drugs, National Institutes for Food and Drug Control, Key Laboratory of Beijing for Nonclinical Safety Evaluation Research of Drugs, Beijing, 100176, People's Republic of China.
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Hussain Z, Thu HE, Haider M, Khan S, Sohail M, Hussain F, Khan FM, Farooq MA, Shuid AN. A review of imperative concerns against clinical translation of nanomaterials: Unwanted biological interactions of nanomaterials cause serious nanotoxicity. J Drug Deliv Sci Technol 2020. [DOI: 10.1016/j.jddst.2020.101867] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/24/2022]
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Venkatesan K, Kailasam V, Padmanabhan S. Evaluation of titanium dioxide coating on surface roughness of nickel-titanium archwires and its influence on Streptococcus mutans adhesion and enamel mineralization: A prospective clinical study. Am J Orthod Dentofacial Orthop 2020; 158:199-208. [PMID: 32576426 DOI: 10.1016/j.ajodo.2019.07.019] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2019] [Revised: 07/01/2019] [Accepted: 07/01/2019] [Indexed: 11/29/2022]
Abstract
INTRODUCTION This research aimed to evaluate the effect of titanium dioxide (TiO2) coating on surface roughness (Ra) of nickel-titanium (NiTi) archwires and its influence on Streptococcus mutans (S mutans) adhesion and enamel mineralization at the end of 1 month in orthodontic patients and to evaluate the integrity of the TiO2 coating. METHODS Twelve patients undergoing orthodontic treatment with preadjusted edgewise appliance formed the sample for this prospective clinical study. Uncoated NiTi archwires and TiO2 nanoparticle coated NiTi archwires in as-received condition and after 1 month of intraoral use were subjected to Ra analysis using surface profilometry, and surface topography using scanning electron microscopy. S mutans adhesion was evaluated on the retrieved archwires using real-time polymerase chain reaction (PCR). Enamel mineral content in the arches related to the uncoated and coated archwires was evaluated using DIAGNOdent. RESULTS After 1 month of intraoral use, both coated and uncoated archwires exhibited a rougher surface with coated archwires demonstrating greater quantum of increase (control, P = 0.002; experimental, P = 0.002). S mutans adhesion was more in uncoated archwires (P = 0.0005). The TiO2 nanoparticle coating on the NiTi archwires showed delamination, deterioration and was lost by 60% at the end of 1 month. Laser fluorescence values did not show any significant difference (control, P = 0.182; experimental, P = 0.105). CONCLUSIONS TiO2 nanoparticle coating on NiTi archwires causes an initial reduction in roughness; however, at the end of 1 month, the benefit was lost. S mutans adhesion was lesser on the coated wires, which could be attributed to reduced initial Ra and antibacterial property of TiO2. Orthodontic archwire appears to have a limited role in enamel demineralization.
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Affiliation(s)
- Keerthi Venkatesan
- Department of Orthodontics and Dentofacial Orthopedics, Sri Ramachandra Institute of Higher Education and Research, Chennai, Tamil Nadu, India.
| | - Vignesh Kailasam
- Department of Orthodontics and Dentofacial Orthopedics, Sri Ramachandra Institute of Higher Education and Research, Chennai, Tamil Nadu, India
| | - Sridevi Padmanabhan
- Department of Orthodontics and Dentofacial Orthopedics, Sri Ramachandra Institute of Higher Education and Research, Chennai, Tamil Nadu, India
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Ali SH, Sulaiman GM, Al-Halbosiy MMF, Jabir MS, Hameed AH. Fabrication of hesperidin nanoparticles loaded by poly lactic co-Glycolic acid for improved therapeutic efficiency and cytotoxicity. ARTIFICIAL CELLS NANOMEDICINE AND BIOTECHNOLOGY 2019; 47:378-394. [PMID: 30691314 DOI: 10.1080/21691401.2018.1559175] [Citation(s) in RCA: 57] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/27/2022]
Abstract
Hesperidin, as a flavonone, is recognized as promising anti-inflammatory, antioxidant, and anticancer agent. Its poor bioavailability is crucial bottleneck for therapeutic efficacy. To enhance the stability and bioactive potentials, hesperidin -PLGA-Poloxamer 407 was successfully prepared to minimize or overcome problems associated with hesperidin absorption. The characteristics of nanohesperidin were testing by in vitro dissolution study, XRD, FTIR, PSA and SEM. Antioxidant effects of nanohesperidin were studied. The structure-activity relationship analysis with antioxidant pharmacophore has been performed by using density functional theory method and quantum chemical calculations. The structural properties were investigated using Becke three-parameter hybrid exchange and the Lee-Yang-Parr correction functional methods. Nanohesperidin was found to decrease the H2O2 activity-induced DNA instability. Blood compatibility on human erythrocytes was confirmed by haemolytic and in vitro toxicity assessments. The in vitro anticancer activity of nanohesperidin towards MCF-7 cells using various parameters was carried out. The nanohesperidin was found to exert cell growth arrest, activated DNA fragmentation and induced apoptotic cell death through caspase-3 and p53-dependent pathways. These findings showed that nanohesperidin play an important role in its anticancer effects, suggesting might be used for clinical trials and can represent driving formulation for novel chemotherapeutic agents.
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Affiliation(s)
- Saja H Ali
- a Biotechnology Division, Applied Science Department , University of Technology , Baghdad , Iraq
| | - Ghassan M Sulaiman
- a Biotechnology Division, Applied Science Department , University of Technology , Baghdad , Iraq
| | | | - Majid S Jabir
- a Biotechnology Division, Applied Science Department , University of Technology , Baghdad , Iraq
| | - Anaheed H Hameed
- a Biotechnology Division, Applied Science Department , University of Technology , Baghdad , Iraq
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Schulte P, Leso V, Niang M, Iavicoli I. Biological monitoring of workers exposed to engineered nanomaterials. Toxicol Lett 2018; 298:112-124. [PMID: 29920308 PMCID: PMC6239923 DOI: 10.1016/j.toxlet.2018.06.003] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2018] [Revised: 05/29/2018] [Accepted: 06/08/2018] [Indexed: 12/27/2022]
Abstract
As the number of nanomaterial workers increase there is need to consider whether biomonitoring of exposure should be used as a routine risk management tool. Currently, no biomonitoring of nanomaterials is mandated by authoritative or regulatory agencies. However, there is a growing knowledge base to support such biomonitoring, but further research is needed as are investigations of priorities for biomonitoring. That research should be focused on validation of biomarkers of exposure and effect. Some biomarkers of effect are generally nonspecific. These biomarkers need further interpretation before they should be used. Overall biomonitoring of nanomaterial workers may be important to supplement risk assessment and risk management efforts.
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Affiliation(s)
- P Schulte
- National Institute for Occupational Safety and Health, Centers for Disease Control and Prevention, 1090 Tusculum Avenue, MS C-14, Cincinnati, OH 45226, USA.
| | - V Leso
- Department of Public Health, University of Naples Federico II, Via S. Pansini 5, 80131 Naples, Italy
| | - M Niang
- University of Cincinnati, Cincinnati, OH, USA
| | - I Iavicoli
- Department of Public Health, University of Naples Federico II, Via S. Pansini 5, 80131 Naples, Italy
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Sutunkova MP, Privalova LI, Minigalieva IA, Gurvich VB, Panov VG, Katsnelson BA. The most important inferences from the Ekaterinburg nanotoxicology team's animal experiments assessing adverse health effects of metallic and metal oxide nanoparticles. Toxicol Rep 2018; 5:363-376. [PMID: 29854606 PMCID: PMC5977416 DOI: 10.1016/j.toxrep.2018.03.008] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2018] [Revised: 03/01/2018] [Accepted: 03/05/2018] [Indexed: 01/01/2023] Open
Abstract
During 2009-2017 we have studied nanoparticles of elemental silver or gold and of iron, copper, nickel, manganese, lead, zinc, aluminium and titanium oxides (Me-NPs) using, in most cases, a single low-dose intratracheal instillation 24 h before the bronchoalveolar lavage to obtain a fluid for cytological and biochemical assessment and, in all cases, repeated intraperitoneal injections in non-lethal doses to induce subchronic intoxications assessed by a lot of toxicodynamic and toxicokinetic features. We have also studied the same effects for a number of relevant combinations of these Me-NPs and have revealed some important patterns of their combined toxicity. Besides, we have carried out long-term inhalation experiments with Fe2O3, NiO and amorphous SiO2 nano-aerosols. We have demonstrated that Me-NPs are much more noxious as compared with their fine micrometric counterparts although the physiological mechanisms of their elimination from the lungs proved to be highly active. Even if water-insoluble, Me-NPs are significantly solubilized in some biological milieus in vitro and in vivo, which may explain some important peculiarities of their toxicity. At the same time, the in situ cytotoxicity, organ-systemic toxicity and in vivo genotoxicity of Me-NPs strongly depends on specific mechanisms characteristic of a particular metal. For some of the Me-NPs studied, we have proposed standards of presumably safe concentrations in workplace air. Along with this, we have proved that the adverse effects of Me-NPs could be significantly alleviated by background or preliminary administration of adequately composed combinations of some bioprotectors.
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Affiliation(s)
- Marina P. Sutunkova
- The Ekaterinburg Medical Research Center for Prophylaxis and Health Protection in Industrial Workers, Ekaterinburg, 620014, Russia
| | - Larisa I. Privalova
- The Ekaterinburg Medical Research Center for Prophylaxis and Health Protection in Industrial Workers, Ekaterinburg, 620014, Russia
| | - Ilzira A. Minigalieva
- The Ekaterinburg Medical Research Center for Prophylaxis and Health Protection in Industrial Workers, Ekaterinburg, 620014, Russia
| | - Vladimir B. Gurvich
- The Ekaterinburg Medical Research Center for Prophylaxis and Health Protection in Industrial Workers, Ekaterinburg, 620014, Russia
| | - Vladimir G. Panov
- Institute of Industrial Ecology of Ural Branch of Russian Academy of Science, Ekaterinburg, 620990, Russia
| | - Boris A. Katsnelson
- The Ekaterinburg Medical Research Center for Prophylaxis and Health Protection in Industrial Workers, Ekaterinburg, 620014, Russia
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14
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Schneider T, Westermann M, Glei M. In vitro uptake and toxicity studies of metal nanoparticles and metal oxide nanoparticles in human HT29 cells. Arch Toxicol 2017; 91:3517-3527. [PMID: 28466231 DOI: 10.1007/s00204-017-1976-z] [Citation(s) in RCA: 46] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2016] [Accepted: 04/26/2017] [Indexed: 11/25/2022]
Abstract
In this paper, we investigated the toxicological behavior of metal nanoparticles (gold, silver) and metal oxide nanoparticles (copper oxide, zinc oxide, titanium dioxide) in vitro in human colorectal adenocarcinoma cells (HT29). We analyzed the cellular uptake by ICP-MS and TEM, the influence on cell viability by MTT assay and trypan blue exclusion test, their effect on DNA damage and/or generation of oxidized bases by alkaline comet assay, and their potential to induce apoptosis by flow cytometry after 24-h nanoparticle treatment with concentrations between 2 and 10 µg/ml. We determined the amount of metal taken up by a single HT29 cell, ranging from 0.02 pg/cell up to 1.39 pg/cell. Cell viability assays showed a significantly decrease for metal oxide nanoparticles using trypan blue exclusion test and for all nanoparticles, except titanium dioxide, using MTT assay. Genotoxic effects after nanoparticle treatment were not observed for the tested concentrations. Apoptosis induction was significantly increased for silver nanoparticles (tested for two sizes) as well as for titanium dioxide and zinc oxide nanoparticles. Our results indicate potential health risks of oral NP uptake by food ingredients or food contamination, making further mechanistic investigations on cellular uptake and toxicity necessary.
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Affiliation(s)
- Thomas Schneider
- Department of Nutritional Toxicology, Institute of Nutrition, Friedrich Schiller University Jena, Dornburger Str. 24, Jena, Germany.
| | - Martin Westermann
- Electron Microscopy Center, University Hospital Jena, Ziegelmühlenweg 1, Jena, Germany
| | - Michael Glei
- Department of Nutritional Toxicology, Institute of Nutrition, Friedrich Schiller University Jena, Dornburger Str. 24, Jena, Germany
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15
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Katsnelson BA, Privalova LI, Sutunkova MP, Minigalieva IA, Gurvich VB, Shur VY, Shishkina EV, Makeyev OH, Valamina IE, Varaksin AN, Panov VG. Experimental Research into Metallic and Metal Oxide Nanoparticle Toxicity In Vivo. BIOACTIVITY OF ENGINEERED NANOPARTICLES 2017. [DOI: 10.1007/978-981-10-5864-6_11] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
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16
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Guo X, Li Y, Yan J, Ingle T, Jones MY, Mei N, Boudreau MD, Cunningham CK, Abbas M, Paredes AM, Zhou T, Moore MM, Howard PC, Chen T. Size- and coating-dependent cytotoxicity and genotoxicity of silver nanoparticles evaluated using in vitro standard assays. Nanotoxicology 2016; 10:1373-84. [PMID: 27441588 DOI: 10.1080/17435390.2016.1214764] [Citation(s) in RCA: 68] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/21/2022]
Abstract
The physicochemical characteristics of silver nanoparticles (AgNPs) may greatly alter their toxicological potential. To explore the effects of size and coating on the cytotoxicity and genotoxicity of AgNPs, six different types of AgNPs, having three different sizes and two different coatings, were investigated using the Ames test, mouse lymphoma assay (MLA) and in vitro micronucleus assay. The genotoxicities of silver acetate and silver nitrate were evaluated to compare the genotoxicity of nanosilver to that of ionic silver. The Ames test produced inconclusive results for all types of the silver materials due to the high toxicity of silver to the test bacteria and the lack of entry of the nanoparticles into the cells. Treatment of L5718Y cells with AgNPs and ionic silver resulted in concentration-dependent cytotoxicity, mutagenicity in the Tk gene and the induction of micronuclei from exposure to nearly every type of the silver materials. Treatment of TK6 cells with these silver materials also resulted in concentration-dependent cytotoxicity and significantly increased micronucleus frequency. With both the MLA and micronucleus assays, the smaller the AgNPs, the greater the cytotoxicity and genotoxicity. The coatings had less effect on the relative genotoxicity of AgNPs than the particle size. Loss of heterozygosity analysis of the induced Tk mutants indicated that the types of mutations induced by AgNPs were different from those of ionic silver. These results suggest that AgNPs induce cytotoxicity and genotoxicity in a size- and coating-dependent manner. Furthermore, while the MLA and in vitro micronucleus assay (in both types of cells) are useful to quantitatively measure the genotoxic potencies of AgNPs, the Ames test cannot.
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Affiliation(s)
| | - Yan Li
- a Division of Genetic and Molecular Toxicology
| | - Jian Yan
- a Division of Genetic and Molecular Toxicology
| | | | | | - Nan Mei
- a Division of Genetic and Molecular Toxicology
| | - Mary D Boudreau
- c Division of Biochemical Toxicology , National Center for Toxicological Research, U.S. Food and Drug Administration , Jefferson , AR , USA
| | | | - Mazhar Abbas
- a Division of Genetic and Molecular Toxicology .,d Institute of Molecular Biology and Biotechnology, The University of Lahore , Pakistan , and
| | | | - Tong Zhou
- e Center for Veterinary Medicine, U.S. Food and Drug Administration , Rockville , MD , USA
| | | | | | - Tao Chen
- a Division of Genetic and Molecular Toxicology
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17
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Rudramurthy GR, Swamy MK, Sinniah UR, Ghasemzadeh A. Nanoparticles: Alternatives Against Drug-Resistant Pathogenic Microbes. Molecules 2016; 21:E836. [PMID: 27355939 PMCID: PMC6273897 DOI: 10.3390/molecules21070836] [Citation(s) in RCA: 279] [Impact Index Per Article: 31.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2016] [Revised: 06/17/2016] [Accepted: 06/20/2016] [Indexed: 01/17/2023] Open
Abstract
Antimicrobial substances may be synthetic, semisynthetic, or of natural origin (i.e., from plants and animals). Antimicrobials are considered "miracle drugs" and can determine if an infected patient/animal recovers or dies. However, the misuse of antimicrobials has led to the development of multi-drug-resistant bacteria, which is one of the greatest challenges for healthcare practitioners and is a significant global threat. The major concern with the development of antimicrobial resistance is the spread of resistant organisms. The replacement of conventional antimicrobials by new technology to counteract antimicrobial resistance is ongoing. Nanotechnology-driven innovations provide hope for patients and practitioners in overcoming the problem of drug resistance. Nanomaterials have tremendous potential in both the medical and veterinary fields. Several nanostructures comprising metallic particles have been developed to counteract microbial pathogens. The effectiveness of nanoparticles (NPs) depends on the interaction between the microorganism and the NPs. The development of effective nanomaterials requires in-depth knowledge of the physicochemical properties of NPs and the biological aspects of microorganisms. However, the risks associated with using NPs in healthcare need to be addressed. The present review highlights the antimicrobial effects of various nanomaterials and their potential advantages, drawbacks, or side effects. In addition, this comprehensive information may be useful in the discovery of broad-spectrum antimicrobial drugs for use against multi-drug-resistant microbial pathogens in the near future.
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Affiliation(s)
| | - Mallappa Kumara Swamy
- Department of Crop Science, Faculty of Agriculture, Universiti Putra Malaysia, Serdang, Selangor, Darul Ehsan 43400, Malaysia.
| | - Uma Rani Sinniah
- Department of Crop Science, Faculty of Agriculture, Universiti Putra Malaysia, Serdang, Selangor, Darul Ehsan 43400, Malaysia.
| | - Ali Ghasemzadeh
- Department of Crop Science, Faculty of Agriculture, Universiti Putra Malaysia, Serdang, Selangor, Darul Ehsan 43400, Malaysia.
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18
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Karim Z, Khan MJ, Maskat MY, Adnan R. Immobilization of horseradish peroxidase on β-cyclodextrin-capped silver nanoparticles: Its future aspects in biosensor application. Prep Biochem Biotechnol 2016; 46:321-7. [DOI: 10.1080/10826068.2015.1031389] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/23/2022]
Affiliation(s)
- Zoheb Karim
- Division of Wood Science and Nanocomposite, Department of Material Science, Lulea University of Technology, Lulea, Sweden
| | - Mohd Jahir Khan
- School of Chemical Sciences and Food Technology, Faculty of Science and Technology, Universiti Kebangsaan Malaysia, Bangi, Selangor, Malaysia
- School of Biotechnology, Jawaharlal Nehru University, New Delhi, India
| | - Mohamad Yusof Maskat
- School of Chemical Sciences and Food Technology, Faculty of Science and Technology, Universiti Kebangsaan Malaysia, Bangi, Selangor, Malaysia
| | - Rohana Adnan
- School of Chemical Sciences, Universiti Sains Malaysia, Minden Penang, Malaysia
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19
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20
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Souza TAJ, Franchi LP, Rosa LR, da Veiga MAMS, Takahashi CS. Cytotoxicity and genotoxicity of silver nanoparticles of different sizes in CHO-K1 and CHO-XRS5 cell lines. MUTATION RESEARCH-GENETIC TOXICOLOGY AND ENVIRONMENTAL MUTAGENESIS 2015; 795:70-83. [PMID: 26774669 DOI: 10.1016/j.mrgentox.2015.11.002] [Citation(s) in RCA: 74] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/20/2015] [Revised: 10/29/2015] [Accepted: 11/05/2015] [Indexed: 01/16/2023]
Abstract
Nanoparticles (NPs) have been used in a range of products due to their unique properties. Nevertheless, these NPs can cause adverse biological effects and because of that, there is a great concern about the health and environmental risks related to their use. Recently, silver nanoparticles (Ag NPs) have been used in a variety of cytotoxicity and genotoxicity studies, but there are still controversies regarding the association between the size and the toxicity of these particles. Therefore, in this study, we aimed to evaluate the cytotoxicity and genotoxicity of Ag NPs (10 and 100 nm) in two different cell lines, CHO-K1 and CHO-XRS5, by performing cell viability assay (XTT), clonogenic assay, micronucleus test, comet assay, as well as by investigating the cell cycle kinetics using the flow cytometry. Cell cultures were exposed to different concentrations of AgNPs (0.025-5.0 μg/ml) for 24 h. Our results indicated that cytotoxicity and genotoxicity induced by the 100 nm-Ag NPs were greater than those induced by the 10 nm-Ag NPs for both cell lines, which suggests that the exposure to greater size particles (100 nm) can cause more adverse biological effects than the exposure to the smaller ones (10 nm).
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Affiliation(s)
- Tiago A J Souza
- Department of Genetics, FMRP-USP, São Paulo University-USP, Ribeirão Preto, SP, Brazil.
| | - Leonardo P Franchi
- Department of Genetics, FMRP-USP, São Paulo University-USP, Ribeirão Preto, SP, Brazil
| | - Lilian R Rosa
- Departament of Chemistry, FFCLRP-USP, São Paulo University-USP, Ribeirão Preto, SP, Brazil
| | - Márcia A M S da Veiga
- Departament of Chemistry, FFCLRP-USP, São Paulo University-USP, Ribeirão Preto, SP, Brazil
| | - Catarina S Takahashi
- Department of Genetics, FMRP-USP, São Paulo University-USP, Ribeirão Preto, SP, Brazil; Departament of Biology, FFCLRP-USP, São Paulo University-USP, Ribeirão Preto, SP, Brazil
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21
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Patlolla AK, Hackett D, Tchounwou PB. Genotoxicity study of silver nanoparticles in bone marrow cells of Sprague-Dawley rats. Food Chem Toxicol 2015; 85:52-60. [PMID: 26032631 PMCID: PMC4659778 DOI: 10.1016/j.fct.2015.05.005] [Citation(s) in RCA: 54] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2015] [Revised: 05/15/2015] [Accepted: 05/16/2015] [Indexed: 12/31/2022]
Abstract
The antimicrobial properties of silver nanoparticles (Ag-NPs) have resulted in their extensive application in consumer and health care products. Although Ag-NPs have great potential benefits, their side effects are unknown and seem inevitable due to their ability to reach the nucleus and damage genetic material. This study aimed to determine genotoxic potential of Ag-NPs using mitotic index (MI), DNA damage (comet assay), structural chromosome aberrations (SCA), micronuclei (MN) formation as genetic endpoints and induction of reactive oxygen species (ROS) as oxidative stress endpoint in bone marrow of Sprague-Dawley rats. Four groups of five male rats were orally administered Ag-NPs, once a day for five days with doses of 5, 25, 50, 100, mg/Kg. A control group was also made of five rats. Bone marrow samples were collected 24 h after the last treatment following standard protocols. Ag-NPs exposure significantly increased (p < 0.05) the induction of ROS, number of SCA, the frequency of micro-nucleated cells, damaged the DNA and decreased the mitotic index compared to negative control. The results suggest that Ag-NPs may have the potential to induce oxidative stress mediated genotoxicity in rats. Further characterization of their genotoxicity and also their potential health implications should be monitored regularly.
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Affiliation(s)
- Anita K Patlolla
- NIH-RCMI Center for Environmental Health, College of Science Engineering and Technology, Jackson State University, Jackson, MS, USA.
| | - Diahanna Hackett
- NIH-RCMI Center for Environmental Health, College of Science Engineering and Technology, Jackson State University, Jackson, MS, USA; Department of Biology-LS-MAMP Program, CSET, Jackson State University, Jackson, MS, USA
| | - Paul B Tchounwou
- NIH-RCMI Center for Environmental Health, College of Science Engineering and Technology, Jackson State University, Jackson, MS, USA
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22
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Franchi LP, Manshian BB, de Souza TA, Soenen SJ, Matsubara EY, Rosolen JM, Takahashi CS. Cyto- and genotoxic effects of metallic nanoparticles in untransformed human fibroblast. Toxicol In Vitro 2015; 29:1319-31. [DOI: 10.1016/j.tiv.2015.05.010] [Citation(s) in RCA: 56] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2015] [Revised: 04/25/2015] [Accepted: 05/16/2015] [Indexed: 02/06/2023]
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23
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Møller P, Hemmingsen JG, Jensen DM, Danielsen PH, Karottki DG, Jantzen K, Roursgaard M, Cao Y, Kermanizadeh A, Klingberg H, Christophersen DV, Hersoug LG, Loft S. Applications of the comet assay in particle toxicology: air pollution and engineered nanomaterials exposure. Mutagenesis 2015; 30:67-83. [PMID: 25527730 DOI: 10.1093/mutage/geu035] [Citation(s) in RCA: 52] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022] Open
Abstract
Exposure to ambient air particles is associated with elevated levels of DNA strand breaks (SBs) and endonuclease III, formamidopyrimidine DNA glycosylase (FPG) and oxoguanine DNA glycosylase-sensitive sites in cell cultures, animals and humans. In both animals and cell cultures, increases in SB and in oxidatively damaged DNA are seen after exposure to a range of engineered nanomaterials (ENMs), including carbon black, carbon nanotubes, fullerene C60, ZnO, silver and gold. Exposure to TiO2 has generated mixed data with regard to SB and oxidatively damaged DNA in cell cultures. Nanosilica does not seem to be associated with generation of FPG-sensitive sites in cell cultures, while large differences in SB generation between studies have been noted. Single-dose airway exposure to nanosized carbon black and multi-walled carbon nanotubes in animal models seems to be associated with elevated DNA damage levels in lung tissue in comparison to similar exposure to TiO2 and fullerene C60. Oral exposure has been associated with augmented DNA damage levels in cells of internal organs, although the doses have been typically very high. Intraveneous and intraperitoneal injection of ENMs have shown contradictory results dependent on the type of ENM and dose in each set of experiments. In conclusion, the exposure to both combustion-derived particles and ENMs is associated with increased levels of DNA damage in the comet assay. Particle size, composition and crystal structure of ENM are considered important determinants of toxicity, whereas their combined contributions to genotoxicity in the comet assay are yet to be thoroughly investigated.
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Affiliation(s)
- Peter Møller
- Department of Public Health, Section of Environmental Health, University of Copenhagen, Øster Farimagsgade 5A, DK-1014 Copenhagen K, Denmark
| | - Jette Gjerke Hemmingsen
- Department of Public Health, Section of Environmental Health, University of Copenhagen, Øster Farimagsgade 5A, DK-1014 Copenhagen K, Denmark
| | - Ditte Marie Jensen
- Department of Public Health, Section of Environmental Health, University of Copenhagen, Øster Farimagsgade 5A, DK-1014 Copenhagen K, Denmark
| | - Pernille Høgh Danielsen
- Department of Public Health, Section of Environmental Health, University of Copenhagen, Øster Farimagsgade 5A, DK-1014 Copenhagen K, Denmark
| | - Dorina Gabriela Karottki
- Department of Public Health, Section of Environmental Health, University of Copenhagen, Øster Farimagsgade 5A, DK-1014 Copenhagen K, Denmark
| | - Kim Jantzen
- Department of Public Health, Section of Environmental Health, University of Copenhagen, Øster Farimagsgade 5A, DK-1014 Copenhagen K, Denmark
| | - Martin Roursgaard
- Department of Public Health, Section of Environmental Health, University of Copenhagen, Øster Farimagsgade 5A, DK-1014 Copenhagen K, Denmark
| | - Yi Cao
- Department of Public Health, Section of Environmental Health, University of Copenhagen, Øster Farimagsgade 5A, DK-1014 Copenhagen K, Denmark
| | - Ali Kermanizadeh
- Department of Public Health, Section of Environmental Health, University of Copenhagen, Øster Farimagsgade 5A, DK-1014 Copenhagen K, Denmark
| | - Henrik Klingberg
- Department of Public Health, Section of Environmental Health, University of Copenhagen, Øster Farimagsgade 5A, DK-1014 Copenhagen K, Denmark
| | - Daniel Vest Christophersen
- Department of Public Health, Section of Environmental Health, University of Copenhagen, Øster Farimagsgade 5A, DK-1014 Copenhagen K, Denmark
| | - Lars-Georg Hersoug
- Department of Public Health, Section of Environmental Health, University of Copenhagen, Øster Farimagsgade 5A, DK-1014 Copenhagen K, Denmark
| | - Steffen Loft
- Department of Public Health, Section of Environmental Health, University of Copenhagen, Øster Farimagsgade 5A, DK-1014 Copenhagen K, Denmark
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24
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Silver nanoparticles-induced cytotoxicity requires ERK activation in human bladder carcinoma cells. Toxicol Lett 2015; 237:237-43. [PMID: 26149761 DOI: 10.1016/j.toxlet.2015.06.1707] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2015] [Revised: 06/29/2015] [Accepted: 06/30/2015] [Indexed: 01/22/2023]
Abstract
Silver nanoparticles are toxic both in vitro and in vivo. We have investigated the possibility to exploit the cytotoxic potential of silver nanoparticles in T24 bladder carcinoma cells using both bare and PolyVinylPyrrolidone-coated silver nanoparticles. We show that the two types of silver nanoparticles promote morphological changes and cytoskeletal disorganization, are cytotoxic and induce cell death. These effects are due to the increased production of reactive oxygen species which are responsible, at least in part, for the sustained activation of ERK1/2. Indeed, both cytotoxicity and ERK1/2 activation are prevented by exposing the cells to the anti-oxidant N-acetylcysteine. Also blocking the ERK1/2 pathway with the MEK inhibitor PD98059 protects the cells from nanoparticles' cytotoxicity. Our findings suggest that ERK activation plays a role in silver nanoparticle-mediated cytotoxicity in T24 cells.
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25
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Butler KS, Peeler DJ, Casey BJ, Dair BJ, Elespuru RK. Silver nanoparticles: correlating nanoparticle size and cellular uptake with genotoxicity. Mutagenesis 2015; 30:577-91. [PMID: 25964273 DOI: 10.1093/mutage/gev020] [Citation(s) in RCA: 106] [Impact Index Per Article: 10.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022] Open
Abstract
The focus of this research was to develop a better understanding of the pertinent physico-chemical properties of silver nanoparticles (AgNPs) that affect genotoxicity, specifically how cellular uptake influences a genotoxic cell response. The genotoxicity of AgNPs was assessed for three potential mechanisms: mutagenicity, clastogenicity and DNA strand-break-based DNA damage. Mutagenicity (reverse mutation assay) was assessed in five bacterial strains of Salmonella typhimurium and Echerichia coli, including TA102 that is sensitive to oxidative DNA damage. AgNPs of all sizes tested (10, 20, 50 and 100nm), along with silver nitrate (AgNO3), were negative for mutagenicity in bacteria. No AgNPs could be identified within the bacteria cells using transmission electron microscopy (TEM), indicating these bacteria lack the ability to actively uptake AgNPs 10nm or larger. Clastogenicity (flow cytometry-based micronucleus assay) and intermediate DNA damage (DNA strand breaks as measured in the Comet assay) were assessed in two mammalian white blood cell lines: Jurkat Clone E6-1 and THP-1. It was observed that micronucleus and Comet assay end points were inversely correlated with AgNP size, with smaller NPs inducing a more genotoxic response. TEM results indicated that AgNPs were confined within intracellular vesicles of mammalian cells and did not penetrate the nucleus. The genotoxicity test results and the effect of AgNO3 controls suggest that silver ions may be the primary, and perhaps only, cause of genotoxicity. Furthermore, since AgNO3 was not mutagenic in the gram-negative bacterial Ames strains tested, the lack of bacterial uptake of the AgNPs may not be the major reason for the lack of genotoxicity observed.
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Affiliation(s)
- Kimberly S Butler
- U.S. Food and Drug Administration, Office of Medical Products and Tobacco, Center for Devices and Radiological Health, Office of Science and Engineering Laboratories, Division of Biology, Chemistry, and Materials Science, 10933 New Hampshire Avenue, Silver Spring, MD 20993, USA
| | - David J Peeler
- U.S. Food and Drug Administration, Office of Medical Products and Tobacco, Center for Devices and Radiological Health, Office of Science and Engineering Laboratories, Division of Biology, Chemistry, and Materials Science, 10933 New Hampshire Avenue, Silver Spring, MD 20993, USA
| | - Brendan J Casey
- U.S. Food and Drug Administration, Office of Medical Products and Tobacco, Center for Devices and Radiological Health, Office of Science and Engineering Laboratories, Division of Biology, Chemistry, and Materials Science, 10933 New Hampshire Avenue, Silver Spring, MD 20993, USA
| | - Benita J Dair
- U.S. Food and Drug Administration, Office of Medical Products and Tobacco, Center for Devices and Radiological Health, Office of Science and Engineering Laboratories, Division of Biology, Chemistry, and Materials Science, 10933 New Hampshire Avenue, Silver Spring, MD 20993, USA
| | - Rosalie K Elespuru
- U.S. Food and Drug Administration, Office of Medical Products and Tobacco, Center for Devices and Radiological Health, Office of Science and Engineering Laboratories, Division of Biology, Chemistry, and Materials Science, 10933 New Hampshire Avenue, Silver Spring, MD 20993, USA
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26
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Katsnelson BA, Privalova LI, Sutunkova MP, Gurvich VB, Loginova NV, Minigalieva IA, Kireyeva EP, Shur VY, Shishkina EV, Beikin YB, Makeyev OH, Valamina IE. Some inferences from in vivo experiments with metal and metal oxide nanoparticles: the pulmonary phagocytosis response, subchronic systemic toxicity and genotoxicity, regulatory proposals, searching for bioprotectors (a self-overview). Int J Nanomedicine 2015; 10:3013-29. [PMID: 25945048 PMCID: PMC4406262 DOI: 10.2147/ijn.s80843] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
Abstract
The purpose of this paper is to overview and summarize previously published results of our experiments on white rats exposed to either a single intratracheal instillation or repeated intraperitoneal injections of silver, gold, iron oxide, copper oxide, nickel oxide, and manganese oxide nanoparticles (NPs) in stable water suspensions without any chemical additives. Based on these results and some corroborating data of other researchers we maintain that these NPs are much more noxious on both cellular and systemic levels as compared with their 1 μm or even submicron counterparts. However, within the nanometer range the dependence of systemic toxicity on particle size is intricate and non-unique due to complex and often contra-directional relationships between the intrinsic biological aggressiveness of the specific NPs, on the one hand, and complex mechanisms that control their biokinetics, on the other. Our data testify to the high activity of the pulmonary phagocytosis of NPs deposited in airways. This fact suggests that safe levels of exposure to airborne NPs are possible in principle. However, there are no reliable foundations for establishing different permissible exposure levels for particles of different size within the nanometric range. For workroom air, such permissible exposure levels of metallic NP can be proposed at this stage, even if tentatively, based on a sufficiently conservative approach of decreasing approximately tenfold the exposure limits officially established for respective micro-scale industrial aerosols. It was shown that against the background of adequately composed combinations of some bioactive agents (comprising pectin, multivitamin-multimineral preparations, some amino acids, and omega-3 polyunsaturated fatty acid) the systemic toxicity and even genotoxicity of metallic NPs could be markedly attenuated. Therefore we believe that, along with decreasing NP-exposures, enhancing organisms’ resistance to their adverse action with the help of such bioprotectors can prove an efficient auxiliary tool of health risk management in occupations connected with them.
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Affiliation(s)
- Boris A Katsnelson
- The Medical Research Center for Prophylaxis and Health Protection in Industrial Workers, Ekaterinburg, Russia
| | - Larisa I Privalova
- The Medical Research Center for Prophylaxis and Health Protection in Industrial Workers, Ekaterinburg, Russia
| | - Marina P Sutunkova
- The Medical Research Center for Prophylaxis and Health Protection in Industrial Workers, Ekaterinburg, Russia
| | - Vladimir B Gurvich
- The Medical Research Center for Prophylaxis and Health Protection in Industrial Workers, Ekaterinburg, Russia
| | - Nadezhda V Loginova
- The Medical Research Center for Prophylaxis and Health Protection in Industrial Workers, Ekaterinburg, Russia
| | - Ilzira A Minigalieva
- The Medical Research Center for Prophylaxis and Health Protection in Industrial Workers, Ekaterinburg, Russia
| | - Ekaterina P Kireyeva
- The Medical Research Center for Prophylaxis and Health Protection in Industrial Workers, Ekaterinburg, Russia
| | - Vladimir Y Shur
- The Institute of Natural Sciences, The Ural Federal University, Ekaterinburg, Russia
| | - Ekaterina V Shishkina
- The Institute of Natural Sciences, The Ural Federal University, Ekaterinburg, Russia
| | - Ya B Beikin
- The City Clinical Diagnostics Centre, Ekaterinburg, Russia
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Paino IMM, Zucolotto V. Poly(vinyl alcohol)-coated silver nanoparticles: activation of neutrophils and nanotoxicology effects in human hepatocarcinoma and mononuclear cells. ENVIRONMENTAL TOXICOLOGY AND PHARMACOLOGY 2015; 39:614-621. [PMID: 25681999 DOI: 10.1016/j.etap.2014.12.012] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/22/2014] [Revised: 12/19/2014] [Accepted: 12/21/2014] [Indexed: 06/04/2023]
Abstract
Silver nanoparticles (AgNps) have been described as important for their excellent biocompatibility, biomedical applications. Nevertheless, AgNps can interact with the immune system which is essential to analyze human exposure to assess their potential risk to health and environment. In general, the primary site for accumulation of nanoparticles has been demonstrated to be the liver. Furthermore, the direct activation of neutrophils or oxidative burst by a given nanoparticle is poorly documented. In this paper, we investigated the cell uptake, apoptosis, necrosis, DNA damage in human hepatocarcinoma cells (HepG2), primary normal human peripheral blood mononuclear cells (PBMC) and the direct activation of primary isolated neutrophils through the oxidative burst on exposure to AgNps coated with Polyvinyl-alcohol (PVA). All cell types were incubated in the presence of 1.0 and 50.0 μM of AgNps-PVA for 24h. A significant cyto- and genotoxic-response and the activation of human neutrophils were induced by AgNps-PVA (p<0.05). Our results revealed that AgNps can interact with the normal isolated neutrophils, PBMC and HepG2 cells in vitro, which opens the way for further studies on the toxicological effects of AgNps in the human immune system response and cancer cells.
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Affiliation(s)
- Iêda Maria Martinez Paino
- Nanomedicine and Nanotoxicology Group, Physics Institute of São Carlos, University of São Paulo, Av. Trab. São Carlense, 400, CEP13566-590 São Carlos, SP, Brazil.
| | - Valtencir Zucolotto
- Nanomedicine and Nanotoxicology Group, Physics Institute of São Carlos, University of São Paulo, Av. Trab. São Carlense, 400, CEP13566-590 São Carlos, SP, Brazil
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Ávalos A, Haza AI, Morales P. Manufactured silver nanoparticles of different sizes induced DNA strand breaks and oxidative DNA damage in hepatoma and leukaemia cells and in dermal and pulmonary fibroblasts. Folia Biol (Praha) 2015; 61:33-42. [PMID: 25958309 DOI: 10.14712/fb2015061010033] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2024]
Abstract
Many classes of silver nanoparticles (AgNPs) have been synthesized and widely applied, but no conclusive information on their potential cytotoxicity and genotoxicity mechanisms is available. Therefore, the purpose of this study was to compare the potential genotoxic effects (DNA strand breaks and oxidative DNA damage) of 4.7 nm coated and 42 nm uncoated AgNPs, using the comet assay, in four relevant human cell lines (hepatoma, leukaemia, and dermal and pulmonary fibroblasts) in order to understand the impact of such nanomaterials on cellular DNA. The results indicated that in all cell lines tested, 4.7 nm coated (0.1-1.6 μg ml⁻¹) and 42 nm uncoated (0.1-6.7 μg ml⁻¹) AgNPs increased DNA strand breaks in a dose- and size-dependent manner following 24 h treatment, the smaller AgNPs being more genotoxic. Human pulmonary fibroblasts showed the highest sensitivity to the AgNPs. A modified comet assay using endonuclease III and formamidopyrimidine- DNA glycosylase restriction enzymes showed that in tumoral and normal human dermal fibroblasts, pyrimidines and purines were oxidatively damaged by both AgNPs, but the damage was not size-dependent. However, in human pulmonary fibroblasts, no oxidative damage was observed after treatment with 42 nm AgNPs. In conclusion, both AgNP sizes induced DNA damage in human cells, and this damage could be related to oxidative stress.
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Affiliation(s)
- A Ávalos
- Departamento de Nutrición, Bromatología y Tecnología de los Alimentos. Facultad de Veterinaria, Universidad Complutense de Madrid, Spain
| | - A I Haza
- Departamento de Nutrición, Bromatología y Tecnología de los Alimentos. Facultad de Veterinaria, Universidad Complutense de Madrid, Spain
| | - P Morales
- Departamento de Nutrición, Bromatología y Tecnología de los Alimentos. Facultad de Veterinaria, Universidad Complutense de Madrid, Spain
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29
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Foldbjerg R, Jiang X, Miclăuş T, Chen C, Autrup H, Beer C. Silver nanoparticles – wolves in sheep's clothing? Toxicol Res (Camb) 2015. [DOI: 10.1039/c4tx00110a] [Citation(s) in RCA: 97] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2023] Open
Abstract
We review the cellular and molecular mechanisms behind silver nanoparticle toxicity and their intracellular fate. In addition, the role of silver ions in the toxicity of silver nanoparticles is discussed.
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Affiliation(s)
- Rasmus Foldbjerg
- Department of Public Health
- Aarhus University
- 8000 Aarhus C
- Denmark
- The Faculty of Medicine
| | - Xiumei Jiang
- Department of Public Health
- Aarhus University
- 8000 Aarhus C
- Denmark
- The National Center for Nanoscience and Technology
| | | | - Chunying Chen
- The National Center for Nanoscience and Technology
- Chinese Academy of Science
- Beijing 100190
- China
| | - Herman Autrup
- Department of Public Health
- Aarhus University
- 8000 Aarhus C
- Denmark
| | - Christiane Beer
- Department of Public Health
- Aarhus University
- 8000 Aarhus C
- Denmark
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30
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Huk A, Izak-Nau E, Reidy B, Boyles M, Duschl A, Lynch I, Dušinska M. Is the toxic potential of nanosilver dependent on its size? Part Fibre Toxicol 2014; 11:65. [PMID: 25466209 PMCID: PMC4274708 DOI: 10.1186/s12989-014-0065-1] [Citation(s) in RCA: 57] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2014] [Accepted: 11/10/2014] [Indexed: 01/07/2023] Open
Abstract
BACKGROUND Nanosilver is one of the most commonly used engineered nanomaterials (ENMs). In our study we focused on assessing the size-dependence of the toxicity of nanosilver (Ag ENMs), utilising materials of three sizes (50, 80 and 200 nm) synthesized by the same method, with the same chemical composition, charge and coating. METHODS Uptake and localisation (by Transmission Electron Microscopy), cell proliferation (Relative growth activity) and cytotoxic effects (Plating efficiency), inflammatory response (induction of IL-8 and MCP-1 by Enzyme linked immune sorbent assay), DNA damage (strand breaks and oxidised DNA lesions by the Comet assay) were all assessed in human lung carcinoma epithelial cells (A549), and the mutagenic potential of ENMs (Mammalian hprt gene mutation test) was assessed in V79-4 cells as per the OECD protocol. Detailed physico-chemical characterization of the ENMs was performed in water and in biological media as a prerequisite to assessment of their impacts on cells. To study the relationship between the surface area of the ENMs and the number of ENMs with the biological response observed, Ag ENMs concentrations were recalculated from μg/cm2 to ENMs cm2/cm2 and ENMs/cm2. RESULTS Studied Ag ENMs are cytotoxic and cytostatic, and induced strand breaks, DNA oxidation, inflammation and gene mutations. Results expressed in mass unit [μg/cm2] suggested that the toxicity of Ag ENMs is size dependent with 50 nm being most toxic. However, re-calculation of Ag ENMs concentrations from mass unit to surface area and number of ENMs per cm2 highlighted that 200 nm Ag ENMs, are the most toxic. Results from hprt gene mutation assay showed that Ag ENMs 200 nm are the most mutagenic irrespective of the concentration unit expressed. CONCLUSION We found that the toxicity of Ag ENMs is not always size dependent. Strong cytotoxic and genotoxic effects were observed in cells exposed to Ag ENMs 50 nm, but Ag ENMs 200 nm had the most mutagenic potential. Additionally, we showed that expression of concentrations of ENMs in mass units is not representative. Number of ENMs or surface area of ENMs (per cm2) seem more precise units with which to compare the toxicity of different ENMs.
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Castiglioni S, Caspani C, Cazzaniga A, Maier JAM. Short- and long-term effects of silver nanoparticles on human microvascular endothelial cells. World J Biol Chem 2014; 5:457-464. [PMID: 25426268 PMCID: PMC4243149 DOI: 10.4331/wjbc.v5.i4.457] [Citation(s) in RCA: 45] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/27/2014] [Revised: 08/01/2014] [Accepted: 09/10/2014] [Indexed: 02/05/2023] Open
Abstract
AIM: To study the response to silver nanoparticles (Ag NP) of human microvascular endothelial cells, protagonists of angiogenesis.
METHODS: We cultured human microvascular endothelial cells and endothelial colony-forming cells in their corresponding growth medium. Stock solutions of Ag NP were prepared in culture medium and sonicated before use. They were added at different concentrations and for different times to culture media. The toxicity of Ag NP was investigated by measuring the reduction of yellow tetrazolium salt to dark purple formazan (MTT assay) at 575 nm. After staining with trypan blue, cell proliferation was assessed by counting viable cells. The lactate dehydrogenase leakage assay was performed on culture media by following the oxidation of NADH to NAD+ and monitoring the reaction kinetically at 340 nm. Reactive oxygen species production was quantified using 2’-7’-dichlorofluorescein diacetate. The alkaline comet assay was performed after mixing the cells with low melting-point agarose. Electrophoresis was then conducted and the samples were stained with ethidium bromide and analyzed with a fluorescence microscope.
RESULTS: Ag NP are cytotoxic in a dose and time dependent fashion for HMEC. At high concentrations, Ag NP determine loss of membrane integrity as demonstrated by the increased activity of lactate dehydrogenase in the culture medium. Ag NP rapidly stimulate the formation of free radicals. However, pre-incubation with Trolox, apocynin, or N-acetyl-L-cysteine, antioxidants which have different structure and act through different mechanisms, is not sufficient to prevent cytotoxicity. Ag NP also induce DNA damage dose-dependently, as shown by comet assay. When exposed to sublethal concentrations of Ag NP for long times, the cells remain viable but are growth retarded. Interestingly, removal of Ag NP partially rescues cell growth. Also genotoxicity is reversible upon removal of Ag NP from culture medium, suggesting that no permanent modifications occur. It is noteworthy that Ag NP are cytotoxic and genotoxic also for endothelial progenitors, in particular for endothelial colony-forming cells, which participate to angiogenesis.
CONCLUSION: Silver nanoparticles are cytotoxic and genotoxic for human microvascular endothelial cells and might become a useful tool to control excessive angiogenesis.
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Xu L, Shi C, Shao A, Li X, Cheng X, Ding R, Wu G, Chou LL. Toxic responses in rat embryonic cells to silver nanoparticles and released silver ions as analyzed via gene expression profiles and transmission electron microscopy. Nanotoxicology 2014; 9:513-22. [DOI: 10.3109/17435390.2014.948942] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
Affiliation(s)
- Liming Xu
- Institute for Medical Device Control, National Institutes for Food and Drug Control, Temple of Heaven, Beijing, People's Republic of China,
- School of Information and Engineering, Wenzhou Medical University, Wenzhou, People's Republic of China,
- Baotou Medical College, Baotou, People's Republic of China,
| | - Chang Shi
- Beijing Institute of Pharmacology and Toxicology, National Beijing Center for Drug Safety Evaluation and Research, Beijing, People's Republic of China,
| | - Anliang Shao
- Institute for Medical Device Control, National Institutes for Food and Drug Control, Temple of Heaven, Beijing, People's Republic of China,
| | - Xuefei Li
- Baotou Medical College, Baotou, People's Republic of China,
- The First Affiliated Hospital, Baotou Medical College, Baotou, People's Republic of China,
| | - Xiang Cheng
- Institute for Medical Device Control, National Institutes for Food and Drug Control, Temple of Heaven, Beijing, People's Republic of China,
- School of Materials Science and Engineering, Southwest Jiaotong University, Chengdu, People's Republic of China, and
| | - Rigao Ding
- Beijing Institute of Pharmacology and Toxicology, National Beijing Center for Drug Safety Evaluation and Research, Beijing, People's Republic of China,
| | - Gang Wu
- The First Affiliated Hospital, Baotou Medical College, Baotou, People's Republic of China,
| | - Laisheng Lee Chou
- Goldman School of Dental Medicine, Boston University, Boston, MA, USA
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Jiang X, Miclăuş T, Wang L, Foldbjerg R, Sutherland DS, Autrup H, Chen C, Beer C. Fast intracellular dissolution and persistent cellular uptake of silver nanoparticles in CHO-K1 cells: implication for cytotoxicity. Nanotoxicology 2014; 9:181-9. [PMID: 24738617 DOI: 10.3109/17435390.2014.907457] [Citation(s) in RCA: 105] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
Toxicity of silver nanoparticles (Ag NPs) has been reported both in vitro and in vivo. However, the intracellular stability and chemical state of Ag NPs are still not very well studied. In this work, we systematically investigated the cellular uptake pathways, intracellular dissolution and chemical species, and cytotoxicity of Ag NPs (15.9 ± 7.6 nm) in Chinese hamster ovary cell subclone K1 cells, a cell line recommended by the OECD for genotoxicity studies. Quantification of intracellular nanoparticle uptake and ion release was performed through inductively coupled plasma mass spectrometry. X-ray absorption near-edge structure (XANES) was employed to assess the chemical state of intracellular silver. The toxic potential of Ag NPs and Ag(+) was evaluated by cell viability, reactive oxygen species (ROS) production and live-dead cell staining. The results suggest that cellular uptake of Ag NPs involves lipid-raft-mediated endocytosis and energy-independent diffusion. The degradation study shows that Ag NPs taken up into cells dissolved quickly and XANES results directly indicated that the internalized Ag was oxidized to Ag-O- species and then stabilized in silver-sulfur (Ag-S-) bonds within the cells. Subsequent cytotoxicity studies show that Ag NPs decrease cell viability and increase ROS production. Pre-incubation with N-acetyl-L-cysteine, an efficient antioxidant and Ag(+) chelator, diminished the cytotoxicity caused by Ag NPs or Ag(+) exposure. Our study suggests that the cytotoxicity mechanism of Ag NPs is related to the intracellular release of silver ions, followed by their binding to SH-groups, presumably coming from amino acids or proteins, and affecting protein functions and the antioxidant defense system of cells.
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Affiliation(s)
- Xiumei Jiang
- National Center for Nanoscience and Technology , Beijing , China
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34
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Zhang Y, Bai Y, Jia J, Gao N, Li Y, Zhang R, Jiang G, Yan B. Perturbation of physiological systems by nanoparticles. Chem Soc Rev 2014; 43:3762-809. [PMID: 24647382 DOI: 10.1039/c3cs60338e] [Citation(s) in RCA: 98] [Impact Index Per Article: 8.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Nanotechnology is having a tremendous impact on our society. However, societal concerns about human safety under nanoparticle exposure may derail the broad application of this promising technology. Nanoparticles may enter the human body via various routes, including respiratory pathways, the digestive tract, skin contact, intravenous injection, and implantation. After absorption, nanoparticles are carried to distal organs by the bloodstream and the lymphatic system. During this process, they interact with biological molecules and perturb physiological systems. Although some ingested or absorbed nanoparticles are eliminated, others remain in the body for a long time. The human body is composed of multiple systems that work together to maintain physiological homeostasis. The unexpected invasion of these systems by nanoparticles disturbs normal cell signaling, impairs cell and organ functions, and may even cause pathological disorders. This review examines the comprehensive health risks of exposure to nanoparticles by discussing how nanoparticles perturb various physiological systems as revealed by animal studies. The potential toxicity of nanoparticles to each physiological system and the implications of disrupting the balance among systems are emphasized.
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Affiliation(s)
- Yi Zhang
- Key Laboratory for Colloid and Interface Chemistry, Ministry of Education, School of Chemistry and Chemical Engineering, Shandong University, Jinan 250100, China.
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35
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36
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Dobrzyńska MM, Gajowik A, Radzikowska J, Lankoff A, Dušinská M, Kruszewski M. Genotoxicity of silver and titanium dioxide nanoparticles in bone marrow cells of rats in vivo. Toxicology 2014; 315:86-91. [DOI: 10.1016/j.tox.2013.11.012] [Citation(s) in RCA: 96] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2013] [Revised: 11/25/2013] [Accepted: 11/27/2013] [Indexed: 01/17/2023]
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37
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Nymark P, Catalán J, Suhonen S, Järventaus H, Birkedal R, Clausen PA, Jensen KA, Vippola M, Savolainen K, Norppa H. Genotoxicity of polyvinylpyrrolidone-coated silver nanoparticles in BEAS 2B cells. Toxicology 2013; 313:38-48. [DOI: 10.1016/j.tox.2012.09.014] [Citation(s) in RCA: 75] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2012] [Accepted: 09/28/2012] [Indexed: 01/10/2023]
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38
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Kumar A, Dhawan A. Genotoxic and carcinogenic potential of engineered nanoparticles: an update. Arch Toxicol 2013; 87:1883-1900. [DOI: 10.1007/s00204-013-1128-z] [Citation(s) in RCA: 108] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2013] [Accepted: 09/09/2013] [Indexed: 12/22/2022]
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39
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Liman R. Genotoxic effects of Bismuth (III) oxide nanoparticles by Allium and Comet assay. CHEMOSPHERE 2013; 93:269-73. [PMID: 23790828 DOI: 10.1016/j.chemosphere.2013.04.076] [Citation(s) in RCA: 55] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/11/2012] [Revised: 02/21/2013] [Accepted: 04/27/2013] [Indexed: 05/25/2023]
Abstract
Genotoxic effects of Bismuth (III) oxide nanoparticles (BONPs) were investigated on the root cells of Allium cepa by Allium and Comet assay. A. cepa roots were treated with the aqueous dispersions of BONPs at five different concentrations (12.5, 25, 50, 75, and 100ppm) for 4h. Exposure of BONPs significantly increased mitotic index (MI) except 12.5ppm, total chromosomal aberrations (CAs) in Allium test. While stickiness chromosome laggards, disturbed anaphase-telophase and anaphase bridges were observed in anaphase-telophase cells, pro-metaphase and c-metaphase in other cells. A significant increase in DNA damage was also observed at all concentrations of BONPs except 12.5ppm by Comet assay. The results were also analyzed statistically by using SPSS for Windows; Duncan's multiple range test was performed. These results indicate that BONPs exhibit genotoxic activity in A. cepa root meristematic cells.
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Affiliation(s)
- Recep Liman
- Usak University, Faculty of Arts and Sciences, Molecular Biology and Genetics Department, 1 Eylül Campus, 64300 Uşak, Turkey.
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40
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Jiang X, Foldbjerg R, Miclaus T, Wang L, Singh R, Hayashi Y, Sutherland D, Chen C, Autrup H, Beer C. Multi-platform genotoxicity analysis of silver nanoparticles in the model cell line CHO-K1. Toxicol Lett 2013; 222:55-63. [PMID: 23872614 DOI: 10.1016/j.toxlet.2013.07.011] [Citation(s) in RCA: 86] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2013] [Revised: 07/09/2013] [Accepted: 07/09/2013] [Indexed: 12/23/2022]
Abstract
Investigation of the genotoxic potential of nanomaterials is essential to evaluate if they pose a cancer risk for exposed workers and consumers. The Chinese hamster ovary cell line CHO-K1 is recommended by the OECD for use in the micronucleus assay and is commonly used for genotoxicity testing. However, studies investigating if this cell line is suitable for the genotoxic evaluation of nanomaterials, including induction of DNA adduct and micronuclei formation, are rare and for silver nanoparticles (Ag NPs) missing. Therefore, we here systematically investigated DNA and chromosomal damage induced by BSA coated Ag NPs (15.9±7.6 nm) in CHO-K1 cells in relation to cellular uptake and intracellular localization, their effects on mitochondrial activity and production of reactive oxygen species (ROS), cell cycle, apoptosis and necrosis. Ag NPs are taken up by CHO-K1 cells and are presumably translocated into endosomes/lysosomes. Our cytotoxicity studies demonstrated a concentration-dependent decrease of mitochondrial activity and increase of intracellular reactive oxygen species (ROS) in CHO-K1 cells following exposure to Ag NPs and Ag⁺ (0-20 μg/ml) for 24h. Annexin V/propidium iodide assay showed that Ag NPs and Ag⁺ induced apoptosis and necrosis, which is in agreement with an increased fraction of cells in subG1 phase of the cell cycle. Genotoxicity studies showed that Ag NPs but also silver ions (Ag⁺) induced bulky-DNA adducts, 8-oxodG and micronuclei formation in a concentration-dependent manner, however, there were quantitative and qualitative differences between the particulate and ionic form of silver. Taken together, our multi-platform genotoxicity and cytotoxicity analysis demonstrates that CHO-K1 cells are suitable for the investigation of genotoxicity of nanoparticles like Ag NPs.
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Affiliation(s)
- Xiumei Jiang
- National Center for Nanoscience and Technology, Chinese Academy of Science, No. 11, Beiyitiao Zhongguancun, Beijing 100190, China
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41
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Roszak J, Stępnik M, Nocuń M, Ferlińska M, Smok-Pieniążek A, Grobelny J, Tomaszewska E, Wąsowicz W, Cieślak M. A strategy for in vitro safety testing of nanotitania-modified textile products. JOURNAL OF HAZARDOUS MATERIALS 2013; 256-257:67-75. [PMID: 23669792 DOI: 10.1016/j.jhazmat.2013.04.022] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/24/2012] [Revised: 04/12/2013] [Accepted: 04/13/2013] [Indexed: 06/02/2023]
Abstract
Titanium dioxide nanomaterials are extensively used in many applications, also for modification of textile materials. Toxicological assessment of such textile materials is currently seldom performed, mainly because of lack of appropriate guidelines. The aim of the study was to assess cytotoxic and genotoxic potential of commercially available TiO2 and TiO2/Ag NMs in pristine form as well as polypropylene fibers modified with the NMs. Both titania NMs showed a cytotoxic effect on BALB/3T3 clone A31 and V79 fibroblasts after 72-h exposure. Both NMs induced a weak genotoxic effect in comet assay, with TiO2/Ag being more active. In vitro micronucleus test on human lymphocytes revealed a weak mutagenic effect of both materials after 24h of exposure. In contrast, no significant increase in micronuclei frequency was observed in the in vitro micronucleus test on V79 fibroblasts. The 24-h extracts prepared from polypropylene fibers modified with TiO2/Ag induced a cytotoxic effect on BALB/3T3 cells which strongly depended on the mode of the fibers manufacturing. The study presents a comprehensive approach to toxicity assessment of textile fibers modified with NMs. Proposed approach may form a good "starting point" for improved future testing strategies.
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Affiliation(s)
- Joanna Roszak
- Nofer Institute of Occupational Medicine, 8 St Teresy St., 91-348 Łódź, Poland
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42
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Magdolenova Z, Collins A, Kumar A, Dhawan A, Stone V, Dusinska M. Mechanisms of genotoxicity. A review of in vitro and in vivo studies with engineered nanoparticles. Nanotoxicology 2013; 8:233-78. [PMID: 23379603 DOI: 10.3109/17435390.2013.773464] [Citation(s) in RCA: 376] [Impact Index Per Article: 31.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
Engineered nanoparticles (NPs) are widely used in different technologies but their unique properties might also cause adverse health effects. In reviewing recent in vitro and in vivo genotoxicity studies we discuss potential mechanisms of genotoxicity induced by NPs. Various factors that may influence genotoxic response, including physico-chemical properties and experimental conditions, are highlighted. From 4346 articles on NP toxicity, 112 describe genotoxicity studies (94 in vitro, 22 in vivo). The most used assays are the comet assay (58 in vitro, 9 in vivo), the micronucleus assay (31 in vitro, 14 in vivo), the chromosome aberrations test (10 in vitro, 1 in vivo) and the bacterial reverse mutation assay (13 studies). We describe advantages and potential problems with different methods and suggest the need for appropriate methodologies to be used for investigation of genotoxic effects of NPs, in vitro and in vivo.
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Affiliation(s)
- Zuzana Magdolenova
- NILU-Norwegian Institute for Air Research, MILK, Health Effects Laboratory , Kjeller , Norway
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Comparative in vivo assessment of some adverse bioeffects of equidimensional gold and silver nanoparticles and the attenuation of nanosilver's effects with a complex of innocuous bioprotectors. Int J Mol Sci 2013; 14:2449-83. [PMID: 23354478 PMCID: PMC3587996 DOI: 10.3390/ijms14022449] [Citation(s) in RCA: 48] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2012] [Revised: 01/08/2013] [Accepted: 01/09/2013] [Indexed: 12/21/2022] Open
Abstract
Stable suspensions of nanogold (NG) and nanosilver (NS) with mean particle diameter 50 and 49 nm, respectively, were prepared by laser ablation of metals in water. To assess rat’s pulmonary phagocytosis response to a single intratracheal instillation of these suspensions, we used optical, transmission electron, and semi-contact atomic force microscopy. NG and NS were also repeatedly injected intraperitoneally into rats at a dose of 10 mg/kg (0.5 mg per mL of deionized water) three times a week, up to 20 injections. A group of rats was thus injected with NS after oral administration of a “bioprotective complex” (BPC) comprised of pectin, multivitamins, some amino acids, calcium, selenium, and omega-3 PUFA. After the termination of the injections, many functional and biochemical indices and histopathological features of the spleen, kidneys and liver were evaluated for signs of toxicity, and accumulation of NG or NS in these organs was measured. From the same rats, we obtained cell suspensions of different tissues for performing the RAPD test. It was demonstrated that, although both nanometals were adversely bioactive in all respects considered in this study, NS was more noxious as compared with NG, and that the BPC tested by us attenuated both the toxicity and genotoxicity of NS.
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