Impact of surface functionalization on the uptake mechanism and toxicity effects of silver nanoparticles in HepG2 cells

Ahmed, Lada Brkić; Milić, Mirta; Pongrac, I; Marjanović, Ana Marija; Mlinarić, Hrvoje; Pavičić, Ivan; Gajović, Srećko; Vrček, Ivana Vinković

doi:10.1016/j.fct.2017.07.016

Cited by 59 publications

(33 citation statements)

References 52 publications

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“…At cellular level, generation of reactive oxygen species (ROS) and oxidative stress, alteration of mitochondrial function, inflammation, and induction of DNA damage have been reported as the most plausible mechanisms of AgNP toxicity, although detailed and consistent data are still missing. We have also demonstrated a similar mode of toxic actions for AgNPs in a wide range of mammalian cells including liver, kidney, and brain cells …”

Section: Introductionsupporting

confidence: 53%

“…Generation of ROS during oxidative stress, as demonstrated by data presented in Figures and , may attack DNA and induce mutagenic lesions. We have already evidenced the genotoxicity of different AgNPs in vitro . Therefore, the genotoxic effect of protein versus polymer‐coated AgNPs was evaluated in all collected body compartments of male and female Wistar rats using the alkaline comet assay.…”

Section: Resultsmentioning

confidence: 99%

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Protein Corona Modulates Distribution and Toxicological Effects of Silver Nanoparticles In Vivo

Barbir

Goessler

Ćurlin

et al. 2019

Part & Part Syst Charact

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Exploitation of silver nanoparticles (AgNPs) in biomedicine represents more than one third of their overall applications. Despite their wide use, detailed toxicokinetic data and information on their action mechanisms in vivo are still scarce. One important obstacle is their fate and transformation patterns in biological environments where AgNPs get a “new face” after interaction with biomolecules, particularly proteins. The impact of protein corona on AgNP effects in vivo is eludicated. The in vivo effects of AgNPs prepared with two different protein coronas, albumin, and metallothionein, with polymer‐coated AgNPs are compared in male and female Wistar rats after intravenous administration. The results demonstrate that the character of the protein coronas on the AgNP surface affects not only distribution, but also oxidative stress response and genotoxicity in tissues of rat exposed to AgNPs. Additionally, sex‐related effects are observed. By emphasizing the importance of protein corona formation and sex‐related response, the obtained data support a reliable evidence base needed for assessing the health risks of the steadily increasing human exposure to AgNPs.

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Section: Introductionsupporting

confidence: 53%

Section: Resultsmentioning

confidence: 99%

Protein Corona Modulates Distribution and Toxicological Effects of Silver Nanoparticles In Vivo

Barbir

Goessler

Ćurlin

et al. 2019

Part & Part Syst Charact

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“…In all studies, the results were statistically evaluated by comparing treated cells to untreated control cells; those with p values of <0.05 were considered positive. Some of the in vitro studies studied the uptake of AgNPs inside the cells, which is an essential determination to prove that there has been contact between the cell organelles and the AgNPs [53,72,73,77,[81][82][83]88,89,91,92,98]. Uptake was demonstrated through several methods such as transmission electronic microscopy (TEM), side scatter (SSC) intensity analysis by flow cytometry, confocal microscopy, Raman spectroscopy and scanning transmission electron microscopy (STEM).…”

Section: In Vitro Studiesmentioning

confidence: 99%

“…Guo et al [72] observed greater effects in citrate-AgNPs than in PVP-AgNPs, although the effect of coating was less important than the effect of size. Brkic et al [89] found that intensity of DNA damage measured by comet tail length and intensity, was dependent on AgNPs coating, with PLL-AgNPs and CTAB-AgNPs the most and least damaging, respectively. Finally, Wang et al [84] observed that uncoated AgNPs caused more DNA damage than PVP-AgNPs in HepG2 cells (comet assay), but the opposite was observed in the MN assay.…”

Section: In Vitro Studiesmentioning

confidence: 99%

Genotoxicity of Silver Nanoparticles

et al. 2020

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Silver nanoparticles (AgNPs) are widely used in diverse sectors such as medicine, food, cosmetics, household items, textiles and electronics. Given the extent of human exposure to AgNPs, information about the toxicological effects of such products is required to ensure their safety. For this reason, we performed a bibliographic review of the genotoxicity studies carried out with AgNPs over the last six years. A total of 43 articles that used well-established standard assays (i.e., in vitro mouse lymphoma assays, in vitro micronucleus tests, in vitro comet assays, in vivo micronucleus tests, in vivo chromosome aberration tests and in vivo comet assays), were selected. The results showed that AgNPs produce genotoxic effects at all DNA damage levels evaluated, in both in vitro and in vivo assays. However, a higher proportion of positive results was obtained in the in vitro studies. Some authors observed that coating and size had an effect on both in vitro and in vivo results. None of the studies included a complete battery of assays, as recommended by ICH and EFSA guidelines, and few of the authors followed OECD guidelines when performing assays. A complete genotoxicological characterization of AgNPs is required for decision-making.

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“…While, to the best of our knowledge, no comparable proteomic study of silver nanoparticle effects in Hep G2 or similar human liver cells is available, the results of the present study are also well in line with previous data on silver nanoparticle toxicity in Hep G2 cells obtained with other methods. Cytotoxicity of nanosilver to Hep G2 cells has been demonstrated (Brkic Ahmed et al, ; Filipak Neto, Cardoso da Silva, Liebel, Voigt, & Oliveira Ribeiro, ) and, more importantly, available data provide strong evidence for a role of oxidative stress in Hep G2 cells exposed to nanoparticulate silver (Brzoska, Meczynska‐Wielgosz, Stepkowski, & Kruszewski, ; Filipak Neto et al, ). Moreover, a proliferative response, as suggested by bioinformatic analysis of our data, has been observed previously (Brzoska et al, ).…”

Section: Discussionmentioning

confidence: 99%

Comparative proteomic analysis of silver nanoparticle effects in human liver and intestinal cells

Braeuning

Oberemm

Görte

et al. 2017

J of Applied Toxicology

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Consumers are orally exposed to nanoparticulate or soluble species of the non-essential element silver due to its use in food contact materials or as a food additive. Potential toxicity of silver nanoparticles has gained special scientific attention. A fraction of ingested ionic or particulate silver is taken up in the intestine and transported to the liver, where it may induce oxidative stress and elicit subsequent adverse responses. Here, we present a comprehensive analysis of global proteomic changes induced in human Hep G2 hepatocarcinoma cells by different concentrations of AgPURE silver nanoparticles or by corresponding concentrations of ionic silver. Bioinformatic analysis of proteomic data confirms and substantiates previous findings on silver-induced alterations related to redox stress, mitochondrial dysfunction, intermediary metabolism, inflammatory responses, posttranslational protein modification and other cellular parameters. Similarities between the effects exerted by the two silver species are in line with the assumption that silver ions released from nanoparticles substantially contribute to their toxicity. Moreover, a comparative bioinformatic evaluation of proteomic effects in hepatic and intestinal cells exerted either by silver nanoparticles or bionic silver is presented. Our results show that, despite remarkable differences at the level of affected proteins in the different cell lines, highly similar biological consequences, corresponding to previous in vivo findings, can be deduced by applying appropriate bioinformatic data mining.

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Impact of surface functionalization on the uptake mechanism and toxicity effects of silver nanoparticles in HepG2 cells

Cited by 59 publications

References 52 publications

Protein Corona Modulates Distribution and Toxicological Effects of Silver Nanoparticles In Vivo

Protein Corona Modulates Distribution and Toxicological Effects of Silver Nanoparticles In Vivo

Genotoxicity of Silver Nanoparticles

Comparative proteomic analysis of silver nanoparticle effects in human liver and intestinal cells

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