Intracellular Uptake and Toxicity of Ag and CuO Nanoparticles: A Comparison Between Nanoparticles and their Corresponding Metal Ions

Cronholm, Pontus; Karlsson, Hanna; Hedberg, Jonas; Lowe, Troy A.; Winnberg, Lina; Elihn, Karine; Wallinder, Inger Odnevall; Möller, Lennart

doi:10.1002/smll.201201069

Cited by 283 publications

(222 citation statements)

References 41 publications

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“…The cytotoxicity of CuO NPs on Caco2 cells showed a number of similarities with the results observed by Cronholm et al (2013). There are no clear aggregates on the TEM image (Fig.…”

Section: Resultssupporting

confidence: 78%

Toxicity of antimony, copper, cobalt, manganese, titanium and zinc oxide nanoparticles for the alveolar and intestinal epithelial barrier cells in vitro

et al. 2016

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Heavy metals are found naturally on Earth and exposure to them in the living environment is increasing as a consequence of human activity. The toxicity of six different metal oxide nanoparticles (NP) at different points in time was compared using resazurin assay. After incubating Caco2 and A549 cells with 100 lg/mL of Sb 2 O 3 , Mn 3 O 4 and TiO 2 nanoparticles (NPs) for 24 h no toxic effects were observed while Co 3 O 4 and ZnO NPs had moderate effects and CuO NPs were toxic below 100 lg/mL (24 h EC 25 = 11 for A549 and 71 lg/mL for Caco2). The long-term monitoring (up to 9 days) of cells to NPs revealed that the toxic effects of Mn 3 O 4 and Sb 2 O 3 NPs remarkably increased over time. The 9 day EC 50 values for Sb 2 O 3 NPs were 22 and 48 lg/mL for A549 and Caco2 cells; and for Mn 3 O 4 NPs were 47 and 29 lg/mL for A549 and Caco2 cells, respectively. In general, the sensitivity of the cell lines in the resazurin assay was comparable. Trans epithelial electrical resistance (TEER) measurements were performed for both cell types exposed to Co 3 O 4 , Sb 2 O 3 and CuO NPs. In TEER assay, the Caco2 cells were more susceptible to the toxic effects of these NPs than A549 cells, where the most toxic NPs were the Sb 2 O 3 NPs: the permeability of the Caco2 cell layer exposed to 10 lg/mL Sb 2 O 3 NPs already increased after 24 h of exposure.Electronic supplementary material The online version of this article

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“…The cytotoxicity of CuO NPs on Caco2 cells showed a number of similarities with the results observed by Cronholm et al (2013). There are no clear aggregates on the TEM image (Fig.…”

Section: Resultssupporting

confidence: 78%

Toxicity of antimony, copper, cobalt, manganese, titanium and zinc oxide nanoparticles for the alveolar and intestinal epithelial barrier cells in vitro

et al. 2016

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“…mechanism, which explained how AgNPs facilitated the release of free toxic silver ions in cells, where the particles entered and were then ionized. [32][33][34] Accordingly, intracellular silver ion release greatly contributed to the antibacterial activities of AgNPs. The surface ligand might also regulate this process in the similar way to what happened in vitro, thus explaining the toxicity order of the four tested AgNPs described earlier.…”

Section: E Coli the Results Inmentioning

confidence: 99%

“…and acidic condition of the organelle (lysosome, etc.) might facilitate the oxidation of the silver core, 32 potentially inducing the generation of more silver ions and ROS, which could trigger the corresponding biological effects, such as antibacterial activities. With regard to the quantification for the percentage of particulate effect, this is still challenging due to the complexity of the antibacterial mode of AgNPs, and the hot debate on this question continues in the related toxicological studies.…”

Section: E Coli the Results Inmentioning

confidence: 99%

Surface ligand controls silver ion release of nanosilver and its antibacterial activity against <em>Escherichia coli</em>

Long¹,

Hu²,

Yan³

et al. 2017

IJN

126

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Understanding the mechanism of nanosilver-dependent antibacterial activity against microorganisms helps optimize the design and usage of the related nanomaterials. In this study, we prepared four kinds of 10 nm-sized silver nanoparticles (AgNPs) with dictated surface chemistry by capping different ligands, including citrate, mercaptopropionic acid, mercaptohexanoic acid, and mercaptopropionic sulfonic acid. Their surface-dependent chemistry and antibacterial activities were investigated. Owing to the weak bond to surface Ag, short carbon chain, and low silver ion attraction, citrate-coated AgNPs caused the highest silver ion release and the strongest antibacterial activity against Escherichia coli , when compared to the other tested AgNPs. The study on the underlying antibacterial mechanisms indicated that cellular membrane uptake of Ag, NAD + /NADH ratio increase, and intracellular reactive oxygen species (ROS) generation were significantly induced in both AgNP and silver ion exposure groups. The released silver ions from AgNPs inside cells through a Trojan-horse-type mechanism were suggested to interact with respiratory chain proteins on the membrane, interrupt intracellular O 2 reduction, and induce ROS production. The further oxidative damages of lipid peroxidation and membrane breakdown caused the lethal effect on E. coli . Altogether, this study demonstrated that AgNPs exerted antibacterial activity through the release of silver ions and the subsequent induction of intracellular ROS generation by interacting with the cell membrane. The findings are helpful in guiding the controllable synthesis through the regulation of surface coating for medical care purpose.

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“…Many studies have focused on CuONP-induced cytotoxicity and corresponding mechanisms in human lung epithelial cells. 11,12,[17][18][19] Oxidative stress and autophagy have been reported to play vital roles in CuONPinduced cytotoxicity. 12, 18 Hanagata et al reported that CuONP exposure upregulated genes involved in mitogen-activated protein kinase (MAPK) pathways while downregulating genes involved in cell cycle progression.…”

Section: Introductionmentioning

confidence: 99%

Activation of Erk and p53 regulates copper oxide nanoparticle-induced cytotoxicity in keratinocytes and fibroblasts

Luo¹,

Li²,

Yang³

et al. 2014

IJN

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Copper oxide nanoparticles (CuONP) have attracted increasing attention due to their unique properties and have been extensively utilized in industrial and commercial applications. For example, their antimicrobial capability endows CuONP with applications in dressings and textiles against bacterial infections. Along with the wide applications, concerns about the possible effects of CuONP on humans are also increasing. It is crucial to evaluate the safety and impact of CuONP on humans, and especially the skin, prior to their practical application. The potential toxicity of CuONP to skin keratinocytes has been reported recently. However, the underlying mechanism of toxicity in skin cells has remained unclear. In the present work, we explored the possible mechanism of the cytotoxicity of CuONP in HaCaT human keratinocytes and mouse embryonic fibroblasts (MEF). CuONP exposure induced viability loss, migration inhibition, and G 2 /M phase cycle arrest in both cell types. CuONP significantly induced mitogen-activated protein kinase (extracellular signal-regulated kinase [Erk], p38, and c-Jun N-terminal kinase [JNK]) activation in dose- and time-dependent manners. U0126 (an inhibitor of Erk), but not SB 239063 (an inhibitor of p38) or SP600125 (an inhibitor of JNK), enhanced CuONP-induced viability loss. CuONP also induced decreases in p53 and p-p53 levels in both cell types. Cyclic pifithrin-α, an inhibitor of p53 transcriptional activity, enhanced CuONP-induced viability loss. Nutlin-3α, a p53 stabilizer, prevented CuONP-induced viability loss in HaCaT cells, but not in MEF cells, due to the inherent toxicity of nutlin-3α to MEF. Moreover, the experiments on primary keratinocytes are in accordance with the conclusions acquired from HaCaT and MEF cells. These data demonstrate that the activation of Erk and p53 plays an important role in CuONP-induced cytotoxicity, and agents that preserve Erk or p53 activation may prevent CuONP-induced cytotoxicity.

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Intracellular Uptake and Toxicity of Ag and CuO Nanoparticles: A Comparison Between Nanoparticles and their Corresponding Metal Ions

Abstract: CuO-nano toxicity is predominantly mediated by intracellular uptake and subsequent release of copper ions, whereas no toxicity is observed for Ag-nano due to low release of silver ions within short time periods.

Cited by 283 publications

References 41 publications

Toxicity of antimony, copper, cobalt, manganese, titanium and zinc oxide nanoparticles for the alveolar and intestinal epithelial barrier cells in vitro

Toxicity of antimony, copper, cobalt, manganese, titanium and zinc oxide nanoparticles for the alveolar and intestinal epithelial barrier cells in vitro

Surface ligand controls silver ion release of nanosilver and its antibacterial activity against <em>Escherichia coli</em>

Activation of Erk and p53 regulates copper oxide nanoparticle-induced cytotoxicity in keratinocytes and fibroblasts

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