Toxicity of nano- and ionic silver to embryonic stem cells: a comparative toxicogenomic study

Abstract

BackgroundThe widespread application of silver nanoparticles (AgNPs) and silver-containing products has raised public safety concerns about their adverse effects on human health and the environment. To date, in vitro toxic effects of AgNPs and ionic silver (Ag+) on many somatic cell types are well established. However, no studies have been conducted hitherto to evaluate their effect on cellular transcriptome in embryonic stem cells (ESCs).ResultsThe present study characterized transcriptomic changes induced by 5.0 µg/ml AgNPs during spontaneous differentiation of mouse ESCs, and compared them to those induced by Ag+ under identical conditions. After 24 h exposure, 101 differentially expressed genes (DEGs) were identified in AgNP-treated cells, whereas 400 genes responded to Ag+. Despite the large differences in the numbers of DEGs, functional annotation and pathway analysis of the regulated genes revealed overall similarities between AgNPs and Ag+. In both cases, most of the functions and pathways impacted fell into two major categories, embryonic development and metabolism. Nevertheless, a number of canonical pathways related to cancer were found for Ag+ but not for AgNPs. Conversely, it was noted that several members of the heat shock protein and the metallothionein families were upregulated by AgNPs but not Ag+, suggesting specific oxidative stress effect of AgNPs in ESCs. The effects of AgNPs on oxidative stress and downstream apoptosis were subsequently confirmed by flow cytometry analysis.ConclusionsTaken together, the results presented in the current study demonstrate that both AgNPs and Ag+ caused transcriptomic changes that could potentially exert an adverse effect on development. Although transcriptomic responses to AgNPs and Ag+ were substantially similar, AgNPs exerted specific effects on ESCs due to their nanosized particulate form.Electronic supplementary materialThe online version of this article (doi:10.1186/s12951-017-0265-6) contains supplementary material, which is available to authorized users.

Cytotoxic and Antiproliferative Effects of Nanomaterials on Cancer Cell Lines: A Review

“…These effects in normal cells may be prolonged since harmful impacts remain after AgNP removal [29]. Similar reports were found by Gao, et al, demonstrating that AgNPs can potentially damage mouse embryonic stem cells [30].…”

Size-dependent acute toxicity of silver nanoparticles in mice

“…The toxic potencies of 60 and 100 nm AgNPs are obviously weaker than that of 10 nm AgNP under the condition adjusted by silver concentration. A stimulating effect in which low concentrations of AgNPs accelerate proliferation was reported in mouse embryonic stem cells 23 and HepG2 cells 24 . Taken together, potentially toxic agents might induce cell proliferation rather than cytotoxicity at low levels.…”

<p>Zn-Incorporated TiO2 Nanotube Surface Improves Osteogenesis Ability Through Influencing Immunomodulatory Function of Macrophages</p>

“…In addition, the TNT coating serves as an optimal loading and release platform for inorganic elements such as argentum (Ag) and trace elements including strontium (Sr) and zinc (Zn). 12,24,31 Excess Ag could induce cytotoxicity and DNA damage; 32 while the dose of Sr should be strictly controlled to avoid a deleterious effect during bone formation. 24 On the contrary, Zn is one of the essential trace elements in the body, it could regulate cell proliferation, differentiation and apoptosis, [33][34][35] and a lack of Zn can cause retardation of bone growth.…”