A general mechanism for intracellular toxicity of metal-containing nanoparticles

Sabella, Stefania; Carney, Randy P.; Brunetti, Virgilio; Malvindi, Maria Ada; Al‐Juffali, Noura; Vecchio, Giuseppe; Janes, Sam M.; Bakr, Osman M.; Cingolani, R.; Stellacci, Francesco; Pompa, Pier Paolo

doi:10.1039/c4nr01234h

Cited by 407 publications

(314 citation statements)

References 61 publications

(103 reference statements)

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“…Notably, the cytotoxicity of metallic NPs is frequently associated with leaching metal ions (Sabella et al 2014;Zook et al 2012;Setua et al 2014). Rotoli et al (2012) found that an increase in the permeability of a monolayer of Calu2 cells exposed to CuO, CeO 2 or TiO 2 NPs correlated with a decrease in metabolic activity on the seventh day.…”

Section: Resultsmentioning

confidence: 99%

“…It has been discussed that there could be a linear correlation between short and long-term toxicity (Scheers et al 2001). However, the possibility of exceptions due to various reasons, especially concerning NPs where the particles are covered with biocorona in physiological conditions, has been mentioned earlier (Sabella et al 2014). The need to collect cytotoxicity data over time is derived also from the guidelines of the NICEATM summary of the multicenter evaluation of in vitro cytotoxicity (MEIC) (NICEATM 2001).…”

Section: Introductionmentioning

confidence: 99%

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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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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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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“…Our results showed sporozoite/shell ratio decreases at much lower AgNP concentrations than those of silver ions (statistically significant effects noted at 5 g/ml versus 500 g/ml). One explanation is that the presence of AgNPs contributes to greater silver internalization, potentially mediated by the local low pH enhancing silver release following AgNP binding to the membrane, in an enhanced "Trojan horse" effect which has previously been suggested as a mechanism for nanoparticle toxicology after uptake into lysosomes (29). An alternative is that bound AgNPs are not removed before the excystation assay and thus remain a source of silver ions as sporozoites are excysted, although the results of Su et al suggest the occurrence of sporozoite destruction before the oocyst wall is broken.…”

Section: Discussionmentioning

confidence: 99%

Silver Nanoparticles Decrease the Viability of Cryptosporidium parvum Oocysts

Cameron

Gaiser

Bhandari

et al. 2016

Appl Environ Microbiol

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dOocysts of the waterborne protozoan parasite Cryptosporidium parvum are highly resistant to chlorine disinfection. We show here that both silver nanoparticles (AgNPs) and silver ions significantly decrease oocyst viability, in a dose-dependent manner, between concentrations of 0.005 and 500 g/ml, as assessed by an excystation assay and the shell/sporozoite ratio. For percent excystation, the results are statistically significant for 500 g/ml of AgNPs, with reductions from 83% for the control to 33% with AgNPs. For Ag ions, the results were statistically significant at 500 and 5,000 g/ml, but the percent excystation values were reduced only to 66 and 62%, respectively, from 86% for the control. The sporozoite/shell ratio was affected to a greater extent following AgNP exposure, presumably because sporozoites are destroyed by interaction with NPs. We also demonstrated via hyperspectral imaging that there is a dual mode of interaction, with Ag ions entering the oocyst and destroying the sporozoites while AgNPs interact with the cell wall and, at high concentrations, are able to fully break the oocyst wall.

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“…However, none of these studies could neglect the role of ROS. Thus, it can be stated that ROS production may not be the sole player of DNA damage and some other mechanism may also be responsible for its toxicity like leaching of Au ions from nanoparticles and complexing effect with surrounding biomacromolecules (65,73). Antioxidants have the ability to destroy the ROS and a large number of antioxidants have been reported which have been extensively used in the clinical practice.…”

Section: Special Case: Oxidation Stressmentioning

confidence: 99%

Nanotoxicity of Inert Materials: The Case of Gold, Silver and Iron

et al. 2016

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-Nanotechnology has opened a new horizon of research in various fields including applied physics, chemistry, electronics, optics, robotics, biotechnology and medicine. In the biomedical field, nanomaterials have shown remarkable potential as theranostic agents. Materials which are considered inert are often used in nanomedicine owning to their nontoxic profile. At nanoscale, these inert materials have shown unique properties that differ from bulk and dissolved counterparts. In the case of metals, this unique behavior not only imparts paramount advantages but also confers toxicity due to their unwanted interaction with different cellular processes. In the literature, the toxicity of nanoparticles made from inert materials has been investigated and many of these have revealed toxic potential under specific conditions. The surge to understand underlying mechanism of toxicity has increased and different means have been employed to overcome toxicity problems associated with these agents. In this review, we have focused nanoparticles of three inert metallic materials i.e. gold, silver and iron as these are regarded as biologically inert in the bulk and dissolved form. These materials have gained wider research interest and studies indicating the toxicity of these materials are also emerging. Oxidative stress, physical binding and interference with intracellular signaling are the major role player in nanotoxicity and their predominance is highly dependent upon size, surface coating and administered dose of nanoparticles. Current strategies to overcome toxicity have also been reviewed in the light of recent literature. The authors also suggested that uniform testing standards and well-designed studies are needed to evaluate nanotoxicity of these materials that are otherwise considered as inert.

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A general mechanism for intracellular toxicity of metal-containing nanoparticles

Abstract: We demonstrate a general mechanism for the toxicity induced by metal-containing NPs, named “lysosome-enhanced Trojan horse effect”, which provides design rules to engineer safer NPs.

Cited by 407 publications

References 61 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

Silver Nanoparticles Decrease the Viability of Cryptosporidium parvum Oocysts

Nanotoxicity of Inert Materials: The Case of Gold, Silver and Iron

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