Nanoparticle cytotoxicity depends on intracellular solubility: Comparison of stabilized copper metal and degradable copper oxide nanoparticles

Studer, Andreas M.; Limbach, Ludwig K.; Duc, Luu Van; Krumeich, Frank; Athanassiou, Evagelos K.; Gerber, Leah; Moch, Holger; Stark, Wendelin J.

doi:10.1016/j.toxlet.2010.05.012

Cited by 356 publications

(243 citation statements)

References 51 publications

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“…As such, nano-CuO may follow the ''Trojan horse''-type mechanism (Studer et al, 2010), delivering high concentrations of copper when aggregates dissolve inside the cell due to significantly lower cytoplasmic pH (Johnson & Epel, 1981), creating copper hot-spots, as has been demonstrated for other metal oxide NMs (Gilbert et al, 2012;Xia et al, 2008). Based on the differences in dissolution rates measured in FSW, it is reasonable to hypothesize that the NMs may have accentuated differences in dissolution rates inside the cells where pH is lower and there is higher protein concentration (Studer et al, 2010), resulting in higher solubility and toxicity of synthesized nano-CuO compared with commercial nano-CuO. A high intracellular concentration of Cu 2+ can overwhelm the natural defenses against heavy metals, such as conjugation and effluxing through membrane transporters (Cole & Deeley, 2006).…”

Section: Discussionmentioning

confidence: 99%

Developmental effects of two different copper oxide nanomaterials in sea urchin (Lytechinus pictus) embryos

et al. 2015

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Copper oxide nanomaterials (nano-CuOs) are widely used and can be inadvertently introduced into estuarine and marine environments. We analyzed the effects of different nano-CuOs (a synthesized and a less-pure commercial form), as well as ionic copper (CuSO 4 ) on embryo development in the white sea urchin, a well-known marine model. After 96 h of development with both nano-CuO exposures, we did not detect significant oxidative damage to proteins but did detect decreases in total antioxidant capacity. We show that the physicochemical characteristics of the two nano-CuOs play an essential role in their toxicities. Both nano-CuOs were internalized by embryos and their differential dissolution was the most important toxicological parameter. The synthesized nano-CuO showed greater toxicity (EC 50 ¼ 450 ppb of copper) and had increased dissolution (2.5% by weight over 96 h) as compared with the lesspure commercial nano-CuO (EC 50 ¼ 5395 ppb of copper, 0.73% dissolution by weight over 96 h). Copper caused specific developmental abnormalities in sea urchin embryos including disruption of the aboral-oral axis as a result in changes to the redox environment caused by dissolution of internalized nano-CuO. Abnormal skeleton formation also occurred.

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Section: Discussionmentioning

confidence: 99%

Developmental effects of two different copper oxide nanomaterials in sea urchin (Lytechinus pictus) embryos

et al. 2015

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“…1). For the NPs that released ions at a rapid rate, the short-term hazard effects were identical as those of the dissolved ions (Studer et al 2010). Thus, although higher concentrations of ions were observed during the long-term bioassay, the toxic effects of these ions were already measured during the short-term primary exposure (see CuO and Ag NPs in Table 3).…”

Section: Contributions Of Particles and Ions To Bacterial Toxicitymentioning

confidence: 96%

Evaluation of nano-specific toxicity of zinc oxide, copper oxide, and silver nanoparticles through toxic ratio

Zhang

Bao

et al. 2016

J Nanopart Res

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For safety and environmental risk assessments of nanomaterials (NMs) and to provide essential toxicity data, nano-specific toxicities, or excess toxicities, of ZnO, CuO, and Ag nanoparticles (NPs) (20, 20, and 30 nm, respectively) to Escherichia coli and Saccharomyces cerevisiae in short-term (6 h) and long-term (48 h) bioassays were quantified based on a toxic ratio. ZnO NPs exhibited no nano-specific toxicities, reflecting similar toxicities as ZnO bulk particles (BPs) (as well as zinc salt). However, CuO and Ag NPs yielded distinctly nano-specific toxicities when compared with their BPs. According to their nano-specific toxicities, the capability of these NPs in eliciting hazardous effects on humans and the environment was as follows: CuO > Ag > ZnO NPs. Moreover, long-term bioassays were more sensitive to nano-specific toxicity than short-term bioassays. Overall, nano-specific toxicity is a meaningful measurement to evaluate the environmental risk of NPs. The log T e particle value is a useful parameter for quantifying NP nano-specific toxicity and enabling comparisons of international toxicological data. Furthermore, this value could be used to determine the environmental risk of NPs.

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“…34,35 In contrast, the ionic forms of these materials could not enter the cells freely due to the presence ARTICLE of membrane barrier. 36 The "Trojan horse" model therefore delineates the potential mechanisms and possible sources responsible for the cytotoxicity of nanomaterials. 37À39 In an attempt to further elucidate the molecular basis of the inhibitory effect of nAg on RNA polymerase-conducted transcription, we teased apart a potential interaction between nAg and RNA polymerase in an acellular system and in cells.…”

Section: Articlementioning

confidence: 99%

Silver Nanoparticles Induced RNA Polymerase-Silver Binding and RNA Transcription Inhibition in Erythroid Progenitor Cells

et al. 2013

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Due to its antimicrobial activity, nanosilver (nAg) has become the most widely used nanomaterial. Thus far, the mechanisms responsible for nAg-induced antimicrobial properties and nAg-mediated toxicity to organisms have not been clearly recognized. Silver (Ag) ions certainly play a crucial role, and the form of nanoparticles can change the dissolution rate, bioavailability, biodistribution, and cellular uptake of Ag. However, whether nAg exerts direct "particle-specific" effects has been under debate. Here we demonstrated that nAg exhibited a robust inhibition on RNA polymerase activity and overall RNA transcription through direct Ag binding to RNA polymerase, which is separated from the cytotoxicity pathway induced by Ag ions. nAg treatment in vitro resulted in reduced hemoglobin concentration in erythroid cells; in vivo administration of nAg in mice caused profound reduction of hemoglobin content in embryonic erythrocytes, associated with anemia in the embryos.Embryonic anemia and general proliferation deficit due to the significant inhibition on RNA synthesis, at least partially, accounted for embryonic developmental retardation upon nAg administration. To date, there is no conclusive answer to the sources of nAg-mediated toxicity: Ag ions or "particlespecific" effects, or both. We here demonstrated that both Ag ions and nAg particles simultaneously existed inside cells, demonstrating the "Trojan horse" effects of nAg particles in posing biological impacts on erythroid cells. Moreover, our results suggested that "particle-specific" effects could be the predominant mediator in eliciting biological influences on erythroid cells under relatively low concentrations of nAg exposure. The combined data highlighted the inhibitory effect of nAg on RNA polymerase activity through a direct reciprocal interaction.

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Nanoparticle cytotoxicity depends on intracellular solubility: Comparison of stabilized copper metal and degradable copper oxide nanoparticles

Cited by 356 publications

References 51 publications

Developmental effects of two different copper oxide nanomaterials in sea urchin (Lytechinus pictus) embryos

Developmental effects of two different copper oxide nanomaterials in sea urchin (Lytechinus pictus) embryos

Evaluation of nano-specific toxicity of zinc oxide, copper oxide, and silver nanoparticles through toxic ratio

Silver Nanoparticles Induced RNA Polymerase-Silver Binding and RNA Transcription Inhibition in Erythroid Progenitor Cells

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