Toxicity screenings of nanomaterials: challenges due to interference with assay processes and components of classic<i>in vitro</i>tests

Guadagnini, Rina; Kenzaoui, Blanka Halamoda; Walker, Laura; Pojana, Giulio; Magdolénová, Zuzana; Bilaničová, Dagmar; Saunders, Margaret; Juillerat‐Jeanneret, Lucienne; Marcomini, Antonio; Huk, Anna; Dušinská, Maria; Fjellsbø, Lise Marie; Marano, Francelyne; Boland, Sonja

doi:10.3109/17435390.2013.829590

Cited by 221 publications

(226 citation statements)

References 27 publications

(44 reference statements)

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“…38,39 To address this issue, a number of control experiments are required to identify any potential NP assay interference, and these effects must be considered while interpreting the final results.…”

mentioning

confidence: 99%

Nanotoxicity: emerging concerns regarding nanomaterial safety and occupational hard metal (WC-Co) nanoparticle exposure

Armstead¹,

Li²

2016

IJN

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mentioning

confidence: 99%

Nanotoxicity: emerging concerns regarding nanomaterial safety and occupational hard metal (WC-Co) nanoparticle exposure

Armstead¹,

Li²

2016

IJN

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“…However, these issues do not preclude the use of HTS approaches to screen for NM‐induced cytotoxicity 60. Assay interferences can be avoided by using label‐free methods 61, 62. Impedance‐based spectroscopy is suggested as a method that does not need markers or dyes, and that has enhanced sensitivity compared to traditional assays 63, 64.…”

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

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112

106

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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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“…3,[19][20][21][22] Although by this definition, a nanosheet with a 1 nm thickness is also considered as a NM, the term NM mostly refers to particulate structures consisting of solid materials for which the terms NMs and nanoparticles (NPs) are used interchangeably. The EMA defines nanotechnology as "the use of tiny structures -less than 1,000 nm across -that are designed to have specific properties".…”

Section: What Are Nmps? Definitionsmentioning

confidence: 99%

“…Expectations for the benefits of these so-called nanomedicinal products (NMPs) are high. 3,4 NMPs can have a great impact in health care, including a reduction…”

Section: Introductionmentioning

confidence: 99%

A comparison of immunotoxic effects of nanomedicinal products with regulatory immunotoxicity testing requirements

Giannakou¹,

Park²,

Jong³

et al. 2016

IJN

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Nanomaterials (NMs) are attractive for biomedical and pharmaceutical applications because of their unique physicochemical and biological properties. A major application area of NMs is drug delivery. Many nanomedicinal products (NMPs) currently on the market or in clinical trials are most often based on liposomal products or polymer conjugates. NMPs can be designed to target specific tissues, eg, tumors. In virtually all cases, NMPs will eventually reach the immune system. It has been shown that most NMs end up in organs of the mononuclear phagocytic system, notably liver and spleen. Adverse immune effects, including allergy, hypersensitivity, and immunosuppression, have been reported after NMP administration. Interactions of NMPs with the immune system may therefore constitute important side effects. Currently, no regulatory documents are specifically dedicated to evaluate the immunotoxicity of NMs or NMPs. Their immunotoxicity assessment is performed based on existing guidelines for conventional substances or medicinal products. Due to the unique properties of NMPs when compared with conventional medicinal products, it is uncertain whether the currently prescribed set of tests provides sufficient information for an adequate evaluation of potential immunotoxicity of NMPs. The aim of this study was therefore, to compare the current regulatory immunotoxicity testing requirements with the accumulating knowledge on immunotoxic effects of NMPs in order to identify potential gaps in the safety assessment. This comparison showed that immunotoxic effects, such as complement activation-related pseudoallergy, myelosuppression, inflammasome activation, and hypersensitivity, are not readily detected by using current testing guidelines. Immunotoxicity of NMPs would be more accurately evaluated by an expanded testing strategy that is equipped to stratify applicable testing for the various types of NMPs.

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Toxicity screenings of nanomaterials: challenges due to interference with assay processes and components of classicin vitrotests

Cited by 221 publications

References 27 publications

Nanotoxicity: emerging concerns regarding nanomaterial safety and occupational hard metal (WC-Co) nanoparticle exposure

Nanotoxicity: emerging concerns regarding nanomaterial safety and occupational hard metal (WC-Co) nanoparticle exposure

High throughput toxicity screening and intracellular detection of nanomaterials

A comparison of immunotoxic effects of nanomedicinal products with regulatory immunotoxicity testing requirements

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