Macrophage inflammatory and metabolic responses to graphene-based nanomaterials differing in size and functionalization

Cicuéndez, Mónica; Fernandes, Márcia Astrês; Ayán-Varela, M.; Oliveira, Helena; Feito, María José; Diez-Orejas, Rosalı́a; Paredes, J.I.; Villar–Rodil, S.; Vila, M.; Portolés, María Teresa; Duarte, Iola F.

doi:10.1016/j.colsurfb.2019.110709

Cited by 31 publications

(36 citation statements)

References 57 publications

(66 reference statements)

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“…Previously, it has been shown that PEGylated nanomaterials are biocompatible and do not cause a severe immune response compared to the original materials. For example, Cicueńdez et al studied the effect of GBNs on macrophages in vitro, and found that the inflammatory response is related to particle size and surface modification (Cicuendez et al, 2020). Smaller-sized nanomaterials induced the pro-inflammatory response of macrophages, while PEGlayted GO did not activate this response.…”

Section: Discussionmentioning

confidence: 99%

Cytotoxicity and Immune Dysfunction of Dendritic Cells Caused by Graphene Oxide

Yang

Pan²,

Chen

et al. 2020

Front. Pharmacol.

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Graphene, known as "black gold", has important applications in various fields. In previous studies, it has been proved that graphene oxide (GO) which is a derivative of graphene has low toxicity. However, the immunotoxicity of GO has not been fully elucidated. In this work, we used DC2.4 cell line to investigate the in vitro immunotoxicity of two types of GO, mono-layer GO (mono-GO) and multi-layer GO (multi-GO). We found that mono-GO had less effect on cell viability than multi-GO, but both mono-GO and multi-GO significantly induced the generation of ROS in DC2.4 cells. Interestingly, mono-GO caused DC2.4 cells to aggregate, thus changed the cell morphology significantly. However, no similar influence occurred for multi-GO. In addition, the results showed that these two GOs obviously enhance the release of TNF-a by DC2.4 cells with and without LPS stimulation. GO did not affect the level of IL-6 released from DC2.4 cells, but multi-GO promoted the release of IL-6 while mono-GO inhibited the production of IL-6 when cells were in response to LPS stimulation. Whole-transcriptome sequencing analysis found some immune-related differentially expressed genes including H2-DMb1, Ncbp3, Oas2, Men1, Fas, Cd320, Cd244, and Tinagl1 which are engaged in the immune system process. These results suggested that both mono-GO and multi-GO are immunotoxic to DC2.4 cells, which provides important basis for subsequent biological and clinical medical applications.

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Section: Discussionmentioning

confidence: 99%

Cytotoxicity and Immune Dysfunction of Dendritic Cells Caused by Graphene Oxide

Yang

Pan²,

Chen

et al. 2020

Front. Pharmacol.

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“…Culture of RAW-264.7 Macrophages for Treatment with GO, rGO15, and rGO30 RAW-264.7 macrophages were seeded with cell density of 1 × 10 5 cells/mL in Dulbecco's Modified Eagle Medium (DMEM, Gibco BRL, United Kingdom) supplemented with 10% fetal bovine serum (FBS, Gibco BRL, United Kingdom), 1 mM L-glutamine (BioWhittaker Europe, Verviers, Belgium), 800 µg/mL penicillin (BioWhittaker Europe, Verviers, Belgium), and 800 µg/mL streptomycin (BioWhittaker Europe, Verviers, Belgium) in a 5% CO 2 humidified atmosphere at 37 • C for 24 h. Then, the culture medium was replaced by fresh medium containing GO, rGO15, and rGO30 at different concentrations (1, 5, and 10 µg/mL) that was previously sonicated for 5 min to homogenize the mixture. These doses were chosen based on previous studies with macrophage cultures as an in vitro experimental model [19,65] and considering recent toxicity in vivo studies in mice [66]. After culturing the cells for 24 h under these conditions, the macrophages were first washed with phosphate-buffered saline (PBS, Sigma-Aldrich) to remove the nonincorporated nanomaterials and then detached with a scraper before analyzing all cell response-specific studies.…”

Section: Morphological and Structural Characterization Of Go Rgo15 And Rgo30 Nanostructuresmentioning

confidence: 99%

Benefits in the Macrophage Response Due to Graphene Oxide Reduction by Thermal Treatment

Cicuéndez

Casarrubios

Barroca

et al. 2021

IJMS

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Graphene and its derivatives are very promising nanomaterials for biomedical applications and are proving to be very useful for the preparation of scaffolds for tissue repair. The response of immune cells to these graphene-based materials (GBM) appears to be critical in promoting regeneration, thus, the study of this response is essential before they are used to prepare any type of scaffold. Another relevant factor is the variability of the GBM surface chemistry, namely the type and quantity of oxygen functional groups, which may have an important effect on cell behavior. The response of RAW-264.7 macrophages to graphene oxide (GO) and two types of reduced GO, rGO15 and rGO30, obtained after vacuum-assisted thermal treatment of 15 and 30 min, respectively, was evaluated by analyzing the uptake of these nanostructures, the intracellular content of reactive oxygen species, and specific markers of the proinflammatory M1 phenotype, such as CD80 expression and secretion of inflammatory cytokines TNF-α and IL-6. Our results demonstrate that GO reduction resulted in a decrease of both oxidative stress and proinflammatory cytokine secretion, significantly improving its biocompatibility and potential for the preparation of 3D scaffolds able of triggering the appropriate immune response for tissue regeneration.

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“…Studies have demonstrated that 2D materials can induce immunological system activation with a consequent induction of an inflammatory response (145). This immunological system activation showed itself to be dependent of the 2D materials' physicochemical properties, such as size (106)(107)(108)(109)144), surface chemistry (114,115,123), number of layers, shape (118,119), and functionalization (109,112,114,128,135,139). For example, Yue et al (106) demonstrated that larger graphene oxide (GO) (2 µm) has induced a higher immunological activation than smaller GO (350 nm) both in vitro (peritoneal macrophages) and in vivo (C57BL/6 mice).…”

Section: D Materials and The Immune System: Adverse Effects In In Vitro And In Vivo Modelsmentioning

confidence: 99%

“…Immune cells, such as macrophages and neutrophils, are one of the first line of defense of the immune system; they are capable of engulf the foreign material (or pathogen), degrading it and producing cytokines to enhanced the immune response (150). The uptake of 2D materials by immune system cells have been reported in various studies (31,109,115,126,132); however, there are few studies that address the degradation of those materials after internalization. Mukherjee et al (151) studied the degradation of large and small GO by neutrophils and observed that not only both GO be degraded by neutrophils but also that the product of the degradation was non-toxic to human cells.…”

Section: H Thp-1 Macrophagesmentioning

confidence: 99%

“…Besides to assess the effect of lateral size, Duarte and coworkers ( 109 ) investigated the impacts of two different surfaces functionalization: pegylated graphene oxide (GO-PEG, 200–500 nm) and flavin mononucleotide-stabilized pristine graphene with two different sizes (200–400 nm and 100–200 nm). Their results showed that the cellular uptake of GBMs was mainly influenced by their lateral size, with smaller particles showing greater internalization, while the inflammatory response depended also on the type of functionalization, with GO-PEG showing the lower pro-inflammatory potential.…”

Section: D Materials and The Immune System: Adverse Effects In In Vitro And In Vivo Modelsmentioning

confidence: 99%

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Recent Advances in Immunosafety and Nanoinformatics of Two-Dimensional Materials Applied to Nano-imaging

et al. 2021

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Two-dimensional (2D) materials have emerged as an important class of nanomaterials for technological innovation due to their remarkable physicochemical properties, including sheet-like morphology and minimal thickness, high surface area, tuneable chemical composition, and surface functionalization. These materials are being proposed for new applications in energy, health, and the environment; these are all strategic society sectors toward sustainable development. Specifically, 2D materials for nano-imaging have shown exciting opportunities in in vitro and in vivo models, providing novel molecular imaging techniques such as computed tomography, magnetic resonance imaging, fluorescence and luminescence optical imaging and others. Therefore, given the growing interest in 2D materials, it is mandatory to evaluate their impact on the immune system in a broader sense, because it is responsible for detecting and eliminating foreign agents in living organisms. This mini-review presents an overview on the frontier of research involving 2D materials applications, nano-imaging and their immunosafety aspects. Finally, we highlight the importance of nanoinformatics approaches and computational modeling for a deeper understanding of the links between nanomaterial physicochemical properties and biological responses (immunotoxicity/biocompatibility) towards enabling immunosafety-by-design 2D materials.

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Macrophage inflammatory and metabolic responses to graphene-based nanomaterials differing in size and functionalization

Cited by 31 publications

References 57 publications

Cytotoxicity and Immune Dysfunction of Dendritic Cells Caused by Graphene Oxide

Cytotoxicity and Immune Dysfunction of Dendritic Cells Caused by Graphene Oxide

Benefits in the Macrophage Response Due to Graphene Oxide Reduction by Thermal Treatment

Recent Advances in Immunosafety and Nanoinformatics of Two-Dimensional Materials Applied to Nano-imaging

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