How reversible are the effects of silver nanoparticles on macrophages? A proteomic-instructed view

Dalzon, Bastien; Torres, Anaëlle; Diemer, Hélène; Ravanel, Stéphane; Collin-Faure, Véronique; Pernet‐Gallay, Karin; Jouneau, Pierre‐Henri; Bourguignon, Jacques; Cianférani, Sarah; Carrière, Marie; Aude-Garcia, Catherine; Rabilloud, Thierry

doi:10.1039/c9en00408d

Cited by 22 publications

(50 citation statements)

References 93 publications

(112 reference statements)

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“…Glutathione, a major cellular antioxidant, increased in response to sub‐toxic concentrations of both AgNPs and silver ions, agreeing with the results previously reported for AgNP/Ag + ‐treated keratinocytes and liver cells, as well as for macrophages exposed to silk nanoparticles . Previous proteomic studies of mouse macrophages have shown enzymes involved in glutathione biosynthesis to be induced in response to copper and silver nanoparticles, which was proposed to reflect upregulation of this pathway. The increase in glutamate excretion by AgNP‐exposed cells observed in the present study corroborates this hypothesis, as the cystine‐glutamate antiporter system, which provides cysteine for the rate‐limiting step of GSH synthesis, was reported to be activated in macrophages following pro‐inflammatory stimulation , .…”

Section: Discussionsupporting

confidence: 90%

“…An early work has shown that silver ions could inactivate yeast hexokinase due to binding with protein thiol groups, while a recent metallomics work has highlighted glycolytic enzymes as primary targets of ionic silver in E. coli . Additionally, similar findings, namely decreased activities of hexokinase and enolase, have been recently reported in mouse macrophages exposed to AgNPs . Hence, it is reasonable to postulate that silver‐induced downregulation of macrophage hexokinase, which catalyzes the first and rate‐limiting step of glycolysis, could possibly account for the observed changes in intracellular glucose and extracellular pyruvate.…”

Section: Discussionmentioning

confidence: 72%

“…Accordingly, the metabolism of macrophages has been reported to sensitively respond to exposure to various types of nanoparticles, such as titanium dioxide, silica, poly(lactic‐co‐glycolic acid) and silk nanoparticles , . As for AgNPs, a recent proteomics study in murine macrophages has shown that a subtoxic dose (causing < 20 % decrease in cell viability) of AgNPs (< 100 nm) affected several proteins involved in central metabolism . However, the effects of AgNPs on macrophage metabolome, the most direct readout of altered metabolism, remains to be characterized.…”

Section: Introductionmentioning

confidence: 99%

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Macrophage Metabolomics Reveals Differential Metabolic Responses to Subtoxic Levels of Silver Nanoparticles and Ionic Silver

et al. 2020

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This study employed NMR metabolomics to characterize macrophage responses to subtoxic concentrations of silver nanoparticles (AgNPs ca. 30 nm) and ionic silver (Ag + ), with a view to further elucidate their immunomodulatory activity at the cell metabolism level. Exposure to AgNPs caused RAW 264.7 macrophages to decrease intracellular glucose utilization, possibly due to interference with glycolytic enzymes, and to reprogram the TCA cycle towards anaplerotic fueling and production of anti-inflammatory metabolites (e.g. itaconate and creatine). Moreover, AgNPs-exposed cells were able to control the levels [a] Dr. 1867of reactive oxygen/nitrogen species (ROS/RNS), likely through upregulation of glutathione synthesis. On the other hand, macrophages exposed to Ag + at equivalent subtoxic concentrations showed reduced metabolic activity, lower ability to counterbalance ROS/RNS and alterations in membrane-related lipids. Overall, the metabolomics approach hereby employed provided novel insights into the differential effects of AgNPs and Ag + , which help explain the lower toxic potential of nanosilver than silver ions.ter. Moreover, since the release of silver ions from AgNPs has been highlighted as a main driver of AgNPs toxicity, [23] the metabolic effects of ionic silver (administered as AgNO 3 ), at inhibi-Joana Carrola graduated in Chemistry from the University of Porto, and obtained her PhD in Nanosciences and Nanotechnology, in 2017, from the University of Aveiro. Her PhD research focused on silver nanoparticles metabolism in mammalian cells. She is an expert in metabolomics, with interests in the study of drugs and nanomaterials metabolism.Verónica Bastos obtained her PhD in Biology studying nanotoxicity in in vitro cell cultures at the University of Aveiro, 2016. She is currently a Researcher in a project studying upconversion nanoparticles for multimodal therapy of melanoma at CESAM, Biology department of University of Aveiro. Her main research interests are related to nanotoxicity, nanobiomedicine and cancer therapy, ecotoxicology and human health. Ana Luísa Daniel-da-Silva graduated in Chemical Engineering by Instituto Superior Técnico (Lisbon, Portugal) in 2000 and obtained her PhD degree in Materials Science from the University of Alicante (Spain) in 2005. Since 2009 she is researcher at CICECO-Portugal. Her research focuses on the development of functional nanoparticles and nanocomposites for applications in nanomedicine, bionanotechnology and water remediation. and a member of CICECO-Aveiro Institute of Materials. Her main research interests are: 1) NMR metabolomics of biological systems (biofluids, intact tissues, tissue/material systems, cell cultures) subjected to disease, therapeutics, toxicological or environmental stresses for identification of novel biomarkers; 2) Metabolomic testing of novel biomaterials with applications in biodegradable implants, drug delivery or localized cell recognition; 3) Development of spectroscopy-based methods for food quality control.Conceição Santos is a Full Profes...

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Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 72%

Section: Introductionmentioning

confidence: 99%

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Macrophage Metabolomics Reveals Differential Metabolic Responses to Subtoxic Levels of Silver Nanoparticles and Ionic Silver

et al. 2020

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“…In the supernatant culture of cells exposed to NP and activated by LPS, the concentration of NO and cytokines such as interleukin 6 (IL-6), interleukin 10 (IL-10), monocyte chemoattractant protein-1 (MCP-1) and tumor necrosis factor (TNFa) were measured as prevously described [34,38].…”

Section: No and Cytokines Productionmentioning

confidence: 99%

“…Visualization of F-Actin cytoskeleton was assayed by phalloidin staining according to previously published protocols [38][39][40] 2.8. Glutathione Assays Intracellular glutathione levels were assessed using the monochlorobimane technique, with some modifications [33].…”

Section: F-actin Stainingmentioning

confidence: 99%

Influences of Nanoparticles Characteristics on the Cellular Responses: The Example of Iron Oxide and Macrophages

et al. 2020

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Iron oxide nanoparticles/microparticles are widely present in a variety of environments, e.g., as a byproduct of steel and iron degradation, as, for example, in railway brakes (e.g., metro station) or in welding fumes. As all particulate material, these metallic nanoparticles are taken up by macrophages, a cell type playing a key role in the innate immune response, including pathogen removal phagocytosis, secretion of free radical species such as nitric oxide or by controlling inflammation via cytokine release. In this paper, we evaluated how macrophages functions were altered by two iron based particles of different size (100 nm and 20 nm). We showed that at high, but subtoxic concentrations (1 mg/mL, large nanoparticles induced stronger perturbations in macrophages functions such as phagocytic capacity (tested with fluorescent latex microspheres) and the ability to respond to bacterial endotoxin lipopolysaccharide stimulus (LPS) in secreting nitric oxide and pro-cytokines (e.g., Interleukin-6 (IL-6) and Tumor Necrosis Factor (TNF)). These stronger effects may correlate with an observed stronger uptake of iron for the larger nanoparticles.

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Functionalized Gold Nanoclusters Promote Stress Response in COS‐7 Cells

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Guével

Kosyer

et al. 2023

Advanced NanoBiomed Research

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Ultrasmall gold nanoclusters (AuNC) show great promise for application in theranostics due to their unique optical and physicochemical properties; however, the associated nanotoxicology concerns need to be carefully considered because of their high diffusion across the cellular barrier. Herein, new insights into the role of surface modification of 2 nm AuNC on their toxicity with impact on the metabolism of COS‐7 fibroblast‐like cells are revealed. AuNCs are chemically modified with either a monodentate‐thiolated molecule (AuNC‐MHA) or a modified‐bidentate sulfobetaine zwitterionic molecule (AuNC‐ZwBuEt). Uptake and localization inside fibroblasts and the resultant influence on cell ultrastructure are carefully evaluated using scanning transmission electron microscopy (STEM) and cryo‐soft‐X‐ray tomography (cryo‐SXT). At concentrations of ≥25 μg Au mL−1, AuNC‐ZwBuEt are cytotoxic toward COS‐7 cells and are observed to cross the nuclear membrane. Cryo‐SXT analysis shows that fibroblasts develop an acute stress response in the form of swollen mitochondria, nuclear membrane blebbing, and large cytoplasmic vacuoles as early as 1 h postexposure. By contrast, AuNC‐MHA are not cytotoxic toward COS‐7 cells. Endosomal escape and translocation of the AuNC‐ZwBuEt into the nucleus and other organelles may be the cause for the observed cytotoxicity and highlight the need for further study of metal nanocluster‐cell interactions.

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How reversible are the effects of silver nanoparticles on macrophages? A proteomic-instructed view

Abstract: Silver nanoparticles are known to have profounds effects on living cells, but little is known on how and to which extent cells recover after an acute exposure to silver nanoparticles. This is studied on macrophages in this work.

Cited by 22 publications

References 93 publications

Macrophage Metabolomics Reveals Differential Metabolic Responses to Subtoxic Levels of Silver Nanoparticles and Ionic Silver

Macrophage Metabolomics Reveals Differential Metabolic Responses to Subtoxic Levels of Silver Nanoparticles and Ionic Silver

Influences of Nanoparticles Characteristics on the Cellular Responses: The Example of Iron Oxide and Macrophages

Functionalized Gold Nanoclusters Promote Stress Response in COS‐7 Cells

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