Assessing nanoparticle toxicity in cell-based assays: influence of cell culture parameters and optimized models for bridging the in vitro–in vivo gap

Joris, Freya; Manshian, Bella B.; Peynshaert, Karen; Smedt, Stefaan C. De; Braeckmans, Kevin; Soenen, Stefaan J.

doi:10.1039/c3cs60145e

Cited by 204 publications

(211 citation statements)

References 204 publications

(504 reference statements)

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“…One example is the recent finding that NPs can induce DNA damage and chromosome mutations, as shown for carbon nanotubes that were found to selectively stabilize human telomeric i-motif DNA and inhibit telomerase activity [8]. To progress towards use of NPs without risks, more data are required on the (toxic) effects of NPs on cells, tissues and whole organisms [9]. In order to fulfill the current needs in nanotoxicity research, NPs should be screened rapidly on a variety of cells under standardized conditions, enabling a comparison of data obtained for different materials and between different research groups [10].…”

Section: Introductionmentioning

confidence: 99%

The effect of nanoparticle degradation on poly(methacrylic acid)-coated quantum dot toxicity: The importance of particle functionality assessment in toxicology

et al. 2014

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Colloidal semiconductor nanoparticles (quantum dots) have attracted a lot of interest in technological and biomedical research, given their potent fluorescent properties. However, the use of heavy metal-containing nanoparticles remains an issue of debate. The possible toxic effects of quantum dots remain a hot research topic and several questions such as possible intracellular degradation of quantum dots and the effect thereof on both cell viability and particle functionality remain unresolved. In the present work, poly(methacrylic acid)-coated CdSe/ZnS quantum dots were synthesized and characterized, after which their effects on cultured cells were evaluated using a multiparametric setup. The data reveal that the quantum dots are taken up through endocytosis and when exposed to the low pH of the endosomal structures, they partially degrade and release cadmium ions, which lowers their fluorescence intensity and augments particle toxicity. Using the multiparametric method, the quantum dots were evaluated at nontoxic doses in terms of their ability to visualize labeled cells for longer time periods. The data revealed that comparing different particles in terms of their applied dose is challenging, likely due to difficulties in obtaining accurate nanoparticles concentrations, but evaluating particle toxicity in terms of their biological functionality enables an easy and straightforward comparison.

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Section: Introductionmentioning

confidence: 99%

The effect of nanoparticle degradation on poly(methacrylic acid)-coated quantum dot toxicity: The importance of particle functionality assessment in toxicology

et al. 2014

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“…Furthermore, the ex vivo human whole blood model is a highly suitable model for studying the immunomodulatory effects of engineered nanoparticles. Although this model lacks the complexity of a whole organism, it has major advantages over monoculture models: it minimizes nanoparticle sedimentation, which has shown to have great influence in in vitro nanotoxicity studies, 36 and, most importantly, it allows for intercellular communication and crosstalk with the protein cascades in the blood that are important for initial inflammatory responses. …”

Section: Discussionmentioning

confidence: 99%

Iron oxide nanoparticles induce cytokine secretion in a complement-dependent manner in a human whole blood model

Wolf-Grosse¹,

Rokstad²,

Ali³

et al. 2017

IJN

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Iron oxide nanoparticles (IONPs) are promising nanomaterials for biomedical applications. However, their inflammatory potential has not been fully established. Here, we used a lepirudin anti-coagulated human whole blood model to evaluate the potential of 10 nm IONPs to activate the complement system and induce cytokine production. Reactive oxygen species and cell death were also assessed. The IONPs activated complement, as measured by C3a, C5a and sC5b-9, and induced the production of pro-inflammatory cytokines in a particle-dose dependent manner, with the strongest response at 10 µg/mL IONPs. Complement inhibitors at C3 (compstatin analog Cp40) and C5 (eculizumab) levels completely inhibited complement activation and secretion of inflammatory mediators induced by the IONPs. Additionally, blockade of complement receptors C3aR and C5aR1 significantly reduced the levels of various cytokines, indicating that the particle-induced secretion of inflammatory mediators is mainly C5a and C3a mediated. The IONPs did not induce cell death or reactive oxygen species, which further suggests that complement activation alone was responsible for most of the particle-induced cytokines. These data suggest that the lepirudin anti-coagulated human whole blood model is a valuable ex vivo system to study the inflammatory potential of IONPs. We conclude that IONPs induce complement-mediated cytokine secretion in human whole blood.

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“…Identifying ENMs hazardous to natural organisms is difficult, given the wide variety of NPs, their diverse properties (eg particle material, size, shape, surface, charge, corona) and the complexity of biological entities (eg membrane and media composition, type of cell, cell cycle) [18]. The interaction of inorganic NPs with biological systems can lead to severe cytotoxic effects [17,[19][20][21][22][23][24]. This cytotoxicity of ENMs is reported across a range of studies that highlight the biological impact of the NP exposure [5,[25][26][27][28].…”

Section: Introductionmentioning

confidence: 99%

Nanoparticle–membrane interactions

Contini

Schneemilch

Gaisford

et al. 2017

Journal of Experimental Nanoscience

153

109

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Engineered nanomaterials have a wide range of applications and as a result, are increasingly present in the environment. While they offer new technological opportunities, there is also the potential for adverse impact, in particular through possible toxicity. In this review, we discuss the current state of the art in the experimental characterisation of nanoparticle-membrane interactions relevant to the prediction of toxicity arising from disruption of biological systems. One key point of discussion is the urgent need for more quantitative studies of nano-bio interactions in experimental models of lipid system that mimic in vivo membranes.

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Assessing nanoparticle toxicity in cell-based assays: influence of cell culture parameters and optimized models for bridging the in vitro–in vivo gap

Cited by 204 publications

References 204 publications

The effect of nanoparticle degradation on poly(methacrylic acid)-coated quantum dot toxicity: The importance of particle functionality assessment in toxicology

The effect of nanoparticle degradation on poly(methacrylic acid)-coated quantum dot toxicity: The importance of particle functionality assessment in toxicology

Iron oxide nanoparticles induce cytokine secretion in a complement-dependent manner in a human whole blood model

Nanoparticle–membrane interactions

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