Cytotoxicity screening of 23 engineered nanomaterials using a test matrix of ten cell lines and three different assays

Kröll, Alexandra; Dierker, C.; Rommel, Christina; Hahn, Daniela; Wohlleben, Wendel; Schulze-Isfort, Christian; Göbbert, Christian; Voetz, Matthias; Hardinghaus, Ferdinand; Schnekenburger, Jürgen

doi:10.1186/1743-8977-8-9

Cited by 194 publications

(159 citation statements)

References 52 publications

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“…High throughput in vitro toxicity assays that are widely employed for small molecule drug screening include assays for cell membrane integrity, oxidative stress, apoptosis, proliferation, or metabolic activity [6]. These assays have also been used for NPs toxicity evaluation [7][8][9][10]. Although plate-based assays offer several advantages (e.g., fast, easy, and reproducible), accumulating data show that NP interference with plate-based assay substrates can lead to erroneous data and provide little correlation with in vivo studies [11][12][13][14].…”

Section: Introductionmentioning

confidence: 99%

Evaluation of Viability and Proliferation Profiles on Macrophages Treated with Silica Nanoparticles In Vitro via Plate-Based, Flow Cytometry, and Coulter Counter Assays

Bancos

Tsai

Hackley

et al. 2012

ISRN Nanotechnology

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Nanoparticles (NPs) are known to interfere with many high-throughput cell viability and cell proliferation assays, which complicates the assessment of their potential toxic effects. The aim of this study was to compare viability and proliferation results for colloidal silica (SiO 2 NP; 7 nm) in the RAW 264.7 mouse macrophage cell line using three different techniques: plate-based assays, flow cytometry analysis, and Coulter counter assays. Our data indicate that CellTiter-Blue, XTT, and CyQuant plate-based assays show increased values over control at low SiO 2 NPs concentrations (0.001-0.01 g/L). SiO 2 NPs show little-to-no interference with flow cytometry and Coulter counter assays, which not only were more reliable in determining cell viability and proliferation at low concentrations in vitro, but also identified changes in cell granularity and size that were not captured by the plate-based assays. At high SiO 2 NP concentrations (1 g/L) all techniques indicated cytotoxicity. In conclusion, flow cytometry and Coulter counter identified new cellular features, and flow cytometry offered more flexibility in analyzing the viability and proliferation profile of SiO 2 NP-treated RAW 264.7 cells.

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Section: Introductionmentioning

confidence: 99%

Evaluation of Viability and Proliferation Profiles on Macrophages Treated with Silica Nanoparticles In Vitro via Plate-Based, Flow Cytometry, and Coulter Counter Assays

Bancos

Tsai

Hackley

et al. 2012

ISRN Nanotechnology

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“…A set of sensitive cell lines would also be required to accurately identify NM cytotoxicity. 144 Another limitation is that the NP dose used in in vitro studies often exceeds a realistic relevant dose. Moreover, these in vitro models cannot accurately reproduce various cellular interactions present in the body.…”

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confidence: 99%

Central nervous system toxicity of metallic nanoparticles

Feng¹,

Chen²,

Zhang³

et al. 2015

IJN

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Nanomaterials (NMs) are increasingly used for the therapy, diagnosis, and monitoring of disease- or drug-induced mechanisms in the human biological system. In view of their small size, after certain modifications, NMs have the capacity to bypass or cross the blood–brain barrier. Nanotechnology is particularly advantageous in the field of neurology. Examples may include the utilization of nanoparticle (NP)-based drug carriers to readily cross the blood–brain barrier to treat central nervous system (CNS) diseases, nanoscaffolds for axonal regeneration, nanoelectromechanical systems in neurological operations, and NPs in molecular imaging and CNS imaging. However, NPs can also be potentially hazardous to the CNS in terms of nano-neurotoxicity via several possible mechanisms, such as oxidative stress, autophagy, and lysosome dysfunction, and the activation of certain signaling pathways. In this review, we discuss the dual effect of NMs on the CNS and the mechanisms involved. The limitations of the current research are also discussed.

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“…Assays for cellular metabolic activity, oxidative stress evaluation, apoptosis detection, and cell membrane integrity49, 50, 51, 52, 53, 54, 55 have been developed for analyzing cytotoxicity of chemicals and these are widely used also in NM‐induced cytotoxicity screening. The methods are time‐consuming, labor‐intensive, complex, and in some instances unreliable owing to NM interferences 53, 56, 57.…”

Section: High‐throughput Screening For Nm‐induced Cytotoxicitymentioning

confidence: 99%

High throughput toxicity screening and intracellular detection of nanomaterials

Collins

Annangi

Rubio

et al. 2016

WIREs Nanomed Nanobiotechnol

111

105

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With the growing numbers of nanomaterials (NMs), there is a great demand for rapid and reliable ways of testing NM safety—preferably using in vitro approaches, to avoid the ethical dilemmas associated with animal research. Data are needed for developing intelligent testing strategies for risk assessment of NMs, based on grouping and read‐across approaches. The adoption of high throughput screening (HTS) and high content analysis (HCA) for NM toxicity testing allows the testing of numerous materials at different concentrations and on different types of cells, reduces the effect of inter‐experimental variation, and makes substantial savings in time and cost. HTS/HCA approaches facilitate the classification of key biological indicators of NM‐cell interactions. Validation of in vitro HTS tests is required, taking account of relevance to in vivo results. HTS/HCA approaches are needed to assess dose‐ and time‐dependent toxicity, allowing prediction of in vivo adverse effects. Several HTS/HCA methods are being validated and applied for NM testing in the FP7 project NANoREG, including Label‐free cellular screening of NM uptake, HCA, High throughput flow cytometry, Impedance‐based monitoring, Multiplex analysis of secreted products, and genotoxicity methods—namely High throughput comet assay, High throughput in vitro micronucleus assay, and γH2AX assay. There are several technical challenges with HTS/HCA for NM testing, as toxicity screening needs to be coupled with characterization of NMs in exposure medium prior to the test; possible interference of NMs with HTS/HCA techniques is another concern. Advantages and challenges of HTS/HCA approaches in NM safety are discussed. WIREs Nanomed Nanobiotechnol 2017, 9:e1413. doi: 10.1002/wnan.1413For further resources related to this article, please visit the WIREs website.

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Cytotoxicity screening of 23 engineered nanomaterials using a test matrix of ten cell lines and three different assays

Cited by 194 publications

References 52 publications

Evaluation of Viability and Proliferation Profiles on Macrophages Treated with Silica Nanoparticles In Vitro via Plate-Based, Flow Cytometry, and Coulter Counter Assays

Evaluation of Viability and Proliferation Profiles on Macrophages Treated with Silica Nanoparticles In Vitro via Plate-Based, Flow Cytometry, and Coulter Counter Assays

Central nervous system toxicity of metallic nanoparticles

High throughput toxicity screening and intracellular detection of nanomaterials

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