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The impact of species and cell type on the nanosafety profile of iron oxide nanoparticles in neural cells

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ABSTRACT

Background: While nanotechnology is advancing rapidly, nanosafety tends to lag behind since general mechanistic insights into cell-nanoparticle (NP) interactions remain rare. To tackle this issue, standardization of nanosafety assessment is imperative. In this regard, we believe that the cell type selection should not be overlooked since the applicability of cell lines could be questioned given their altered phenotype. Hence, we evaluated the impact of the cell type on in vitro nanosafety evaluations in a human and murine neuroblastoma cell line, neural progenitor cell line and in neural stem cells. Acute toxicity was evaluated for gold, silver and iron oxide (IO)NPs, and the latter were additionally subjected to a multiparametric analysis to assess sublethal effects.

Results: The stem cells and murine neuroblastoma cell line respectively showed most and least acute cytotoxicity. Using high content imaging, we observed cell type- and species-specific responses to the IONPs on the level of reactive oxygen species production, calcium homeostasis, mitochondrial integrity and cell morphology, indicating that cellular homeostasis is impaired in distinct ways.

Conclusions: Our data reveal cell type-specific toxicity profiles and demonstrate that a single cell line or toxicity end point will not provide sufficient information on in vitro nanosafety. We propose to identify a set of standard cell lines for screening purposes and to select cell types for detailed nanosafety studies based on the intended application and/or expected exposure.

Electronic supplementary material: The online version of this article (doi:10.1186/s12951-016-0220-y) contains supplementary material, which is available to authorized users.

No MeSH data available.


Effect on [Ca2+]c as determined following labelling with Rhod-2 AM. A significant increase in [Ca2+]c was observed in the hNSC and both progenitor cell lines whereas a significant reduction was observed in the remaining three cell types (p < 0.05). Statistical significance is indicated when appropriate (*p < 0.05). NTC not treated control
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Fig3: Effect on [Ca2+]c as determined following labelling with Rhod-2 AM. A significant increase in [Ca2+]c was observed in the hNSC and both progenitor cell lines whereas a significant reduction was observed in the remaining three cell types (p < 0.05). Statistical significance is indicated when appropriate (*p < 0.05). NTC not treated control

Mentions: On the one hand, a significant concentration-dependent increase in [Ca2+]c was observed in the hNSC, ReNcells, and C17.2 cells (Fig. 3). The effect was more severe in the progenitor cell lines compared to the hNSC and the ReNcells showed the highest [Ca2+]c. On the other hand, a decline of the [Ca2+]c was detected in the mNSC, LA-N-2 and Neuro-2a cells. In contrast to previous parameters, the Neuro-2a cells showed more severe effects in terms of the perturbation of the calcium homeostasis. Again, no unambiguous conclusions could be drawn on whether human or murine cell types are more sensitive towards NP exposure.Fig. 3


The impact of species and cell type on the nanosafety profile of iron oxide nanoparticles in neural cells
Effect on [Ca2+]c as determined following labelling with Rhod-2 AM. A significant increase in [Ca2+]c was observed in the hNSC and both progenitor cell lines whereas a significant reduction was observed in the remaining three cell types (p < 0.05). Statistical significance is indicated when appropriate (*p < 0.05). NTC not treated control
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC5017038&req=5

Fig3: Effect on [Ca2+]c as determined following labelling with Rhod-2 AM. A significant increase in [Ca2+]c was observed in the hNSC and both progenitor cell lines whereas a significant reduction was observed in the remaining three cell types (p < 0.05). Statistical significance is indicated when appropriate (*p < 0.05). NTC not treated control
Mentions: On the one hand, a significant concentration-dependent increase in [Ca2+]c was observed in the hNSC, ReNcells, and C17.2 cells (Fig. 3). The effect was more severe in the progenitor cell lines compared to the hNSC and the ReNcells showed the highest [Ca2+]c. On the other hand, a decline of the [Ca2+]c was detected in the mNSC, LA-N-2 and Neuro-2a cells. In contrast to previous parameters, the Neuro-2a cells showed more severe effects in terms of the perturbation of the calcium homeostasis. Again, no unambiguous conclusions could be drawn on whether human or murine cell types are more sensitive towards NP exposure.Fig. 3

View Article: PubMed Central - PubMed

ABSTRACT

Background: While nanotechnology is advancing rapidly, nanosafety tends to lag behind since general mechanistic insights into cell-nanoparticle (NP) interactions remain rare. To tackle this issue, standardization of nanosafety assessment is imperative. In this regard, we believe that the cell type selection should not be overlooked since the applicability of cell lines could be questioned given their altered phenotype. Hence, we evaluated the impact of the cell type on in vitro nanosafety evaluations in a human and murine neuroblastoma cell line, neural progenitor cell line and in neural stem cells. Acute toxicity was evaluated for gold, silver and iron oxide (IO)NPs, and the latter were additionally subjected to a multiparametric analysis to assess sublethal effects.

Results: The stem cells and murine neuroblastoma cell line respectively showed most and least acute cytotoxicity. Using high content imaging, we observed cell type- and species-specific responses to the IONPs on the level of reactive oxygen species production, calcium homeostasis, mitochondrial integrity and cell morphology, indicating that cellular homeostasis is impaired in distinct ways.

Conclusions: Our data reveal cell type-specific toxicity profiles and demonstrate that a single cell line or toxicity end point will not provide sufficient information on in vitro nanosafety. We propose to identify a set of standard cell lines for screening purposes and to select cell types for detailed nanosafety studies based on the intended application and/or expected exposure.

Electronic supplementary material: The online version of this article (doi:10.1186/s12951-016-0220-y) contains supplementary material, which is available to authorized users.

No MeSH data available.