The species origin of the serum in the culture medium influences the in vitro toxicity of silica nanoparticles to HepG2 cells

Pisani, Cédric; Rascol, Estelle; Dorandeu, Christophe; Gaillard, Jean‐Charles; Charnay, Clarence; Guari, Yannick; Chopineau, Joël; Armengaud, Jean; Devoisselle, Jean-Marie; Prat, Odette

doi:10.1371/journal.pone.0182906

Cited by 37 publications

(44 citation statements)

References 47 publications

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“…Consequently, the internalization of PEG M-MSNs is slowed compared to pristine and DMPC M-MSNs. In addition, it is possible that the use of bovine serum in the human cell culture medium may influence internalization and intracellular functional mechanisms, as suggested by Kim et al (2014) and as we demonstrated in a recent publication (Pisani et al 2017b). Indeed, if the cell recognizes the NP-protein complex as non-self, it is probable that this recognition does not take place in vivo, where the corona will be constituted of human proteins recognized as self.…”

Section: M-msn Uptakementioning

confidence: 82%

Biocompatibility assessment of functionalized magnetic mesoporous silica nanoparticles in human HepaRG cells

et al. 2017

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Magnetic mesoporous silica nanoparticles (M-MSNs) are a promising class of nanoparticles for drug delivery. However, a deep understanding of the toxicological mechanisms of action of these nanocarriers is essential, especially in the liver. The potential toxicity on HepaRG cells of pristine, pegylated (PEG), and lipid (DMPC) M-MSNs were compared. Based on MTT assay and real-time cell impedance, none of these NPs presented an extensive toxicity on hepatic cells. However, we observed by transmission electron microscopy (TEM) that the DMPC and pristine M-MSNs were greatly internalized. In comparison, PEG M-MSNs showed a slower cellular uptake. Whole gene expression profiling revealed the M-MSNs molecular modes of action in a time-and dose-dependent manner. The lowest dose tested (1.6 mg/cm 2 ) induced no molecular effect and was defined as 'No Observed Transcriptional Effect level.' The dose 16 mg/cm 2 revealed nascent but transient effects. At the highest dose (80 mg/cm 2 ), adverse effects have clearly arisen and increased over time. The limit of biocompatibility for HepaRG cells could be set at 16 mg/cm 2 for these NPs. Thanks to a comparative pathway-driven analysis, we highlighted the sequence of events that leads to the disruption of hepatobiliary system, elicited by the three types of MMSNs, at the highest dose. The Adverse Outcome Pathway of hepatic cholestasis was implicated. Toxicogenomics applied to cell cultures is an effective tool to characterize and compare the modes of action of many substances. We propose this strategy as an asset for upstream selection of the safest nanocarriers in the framework of regulation for nanobiosafety. ARTICLE HISTORY

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Section: M-msn Uptakementioning

confidence: 82%

Biocompatibility assessment of functionalized magnetic mesoporous silica nanoparticles in human HepaRG cells

et al. 2017

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“…Another relevant parameter which we studied is the effect of different serum concentrations. It was reported that the serum levels have an impact on the genotoxic and acute toxic properties of chemicals and nanoparticles by modulation of their bioavailability and/or alterations of the activity of drug metabolizing enzymes (Wiencke et al, ; Wang and Lee ; Gonzalez et al, ; Lubberstedt et al, ; Pisani et al, ). The serum effect was compound specific; it was observed with certain direct acting chemicals such as CDDP and Etop but not with other substances (MMS and H 2 O 2 ).…”

Section: Discussionmentioning

confidence: 99%

Cytome micronucleus assays with a metabolically competent human derived liver cell line (Huh6): A promising approach for routine testing of chemicals?

Mišík

Nersesyan

Bolognesi

et al. 2018

Environ and Mol Mutagen

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One of the main problems of in vitro genotoxicity tests is the inadequate representation of drug metabolizing enzymes in most indicator cell lines which are currently used. We identified recently a human derived liver cell line (Huh6) which detected induction of DNA damage by representatives of different groups of promutagens without enzyme mix and showed that these cells are more suitable in terms of reproducibility and sensitivity as other currently used liver derived lines. We developed a protocol for micronucleus (MN) cytome assays with these cells and validated the procedure in experiments with representatives of different groups of directly and indirectly acting genotoxic carcinogens (MMS, cisplatin, PhIP, IQ, NDMA, B(a)P, AFB1, etoposide, and H 2 O 2 ). The optimal cytochalasin B concentration in combination with 48 hr treatment was found to be 1.5 μg/mL and leads to a cytokinesis block proliferation index in the range between 1.7 and 2.0. The morphological characteristics of different nuclear anomalies which reflect DNA damage (MN, nuclear bridges, and buds) and their baseline frequencies in untreated cells were characterized, and the rates which are required to cause significant effects were calculated. All compounds caused dose dependent induction of MN when the cells were treated for 24 hr, longer and shorter exposure times were less effective. Experiments with different serum levels (fetal bovine serum [FBS]) showed that 10% FBS in the medium (instead of 4%) causes a substantial increase of the sensitivity of the cells. Our results indicate that the new protocol is a promising approach for routine testing of chemicals. Environ. Mol. Mutagen. 60: 134–144, 2019. © 2018 The Authors. Environmental and Molecular Mutagenesis published by Wiley Periodicals, Inc. on behalf of Environmental Mutagen Society.

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“…Besides, it is worth noting that there is a possibility of the formation of a protein corona, since the samples were dispersed in serum-enriched DMEM. It common in the literature that the corona formed around the nanoparticles lowers its cytotoxicity [43,45,46,47] by lowering its positively-charged surface. …”

Section: Resultsmentioning

confidence: 99%

Response of Fibroblasts MRC-5 to Flufenamic Acid-Grafted MCM-41 Nanoparticles

et al. 2018

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Recently, flufenamic acid (FFA) was discovered among fenamates as a free radical scavenger and gap junction blocker; however, its effects have only been studied in cancer cells. Normal cells in the surroundings of a tumor also respond to radiation, although they are not hit by it directly. This phenomenon is known as the bystander effect, where response molecules pass from tumor cells to normal ones, through communication channels called gap junctions. The use of the enhanced permeability and retention effect, through which drug-loaded nanoparticles smaller than 200 nm may accumulate around a tumor, can prevent the local side effect upon controlled release of the drug. The present work, aimed at functionalizing MCM-41 (Mobil Composition of Matter No. 41) silica nanoparticles with FFA and determining its biocompatibility with human fibroblasts MRC-5 (Medical Research Council cell strain 5). MCM-41, was synthesized and characterized structurally and chemically, with multiple techniques. The biocompatibility assay was performed by Live/Dead technique, with calcein and propidium–iodide. MRC-5 cells were treated with FFA-grafted MCM-41 for 48 h, and 98% of cells remained viable, without signs of necrosis or morphological changes. The results show the feasibility of MCM-41 functionalization with FFA, and its potential protection of normal cells, in comparison to the role of FFA in cancerous ones.

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The species origin of the serum in the culture medium influences the in vitro toxicity of silica nanoparticles to HepG2 cells

Cited by 37 publications

References 47 publications

Biocompatibility assessment of functionalized magnetic mesoporous silica nanoparticles in human HepaRG cells

Biocompatibility assessment of functionalized magnetic mesoporous silica nanoparticles in human HepaRG cells

Cytome micronucleus assays with a metabolically competent human derived liver cell line (Huh6): A promising approach for routine testing of chemicals?

Response of Fibroblasts MRC-5 to Flufenamic Acid-Grafted MCM-41 Nanoparticles

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