Graphene Oxide Elicits Membrane Lipid Changes and Neutrophil Extracellular Trap Formation

Mukherjee, Sourav P.; Lazzaretto, Beatrice; Hultenby, Kjell; Newman, Leon; Rodrigues, Artur Filipe; Lozano, Neus; Kostarelos, Kostas; Malmberg, Per; Fadeel, Bengt

doi:10.1016/j.chempr.2017.12.017

Cited by 71 publications

(77 citation statements)

References 87 publications

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“…Indeed, GO material can penetrate and degrade bacterial and eukaryotic cell membranes, and it has been suggested to breach the C. elegans intestinal barrier . In fact, nematode cells might be particularly susceptible to GO, as they contain a high cholesterol content, and GO has been shown to oxidize cholesterol and to perturb plasma membrane lipid formation . Hence, physical damage to the feeding apparatus and the intestine could account for the smaller body size, as reduced food intake and the resulting metabolic changes correlate with decreased animal length …”

Section: Resultsmentioning

confidence: 99%

“…GO can also adversely affect fecundity; some studies report toxicity to germ cells and reduced fertility in male mice that might depend on elevated cellular reactive oxygen species contents and subsequent DNA damage induction that in turn triggers apoptosis . Accordingly, GO exposure can cause an immune response, involving the activation of macrophages and various interleukins, as well as neutrophil extracellular trap formation similar to pathogen exposure . The degree of toxicity and immune response activation that is observed across studies depend on the GO synthesis protocol and the resulting variability of physicochemical properties, which is determined by the lateral sheet size, vacancy or lattice defects, chemical purity and specific surface functionalization .…”

Section: Introductionmentioning

confidence: 99%

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Improved Biocompatibility of Amino‐Functionalized Graphene Oxide in Caenorhabditis elegans

Rive

Reina

Wagle

et al. 2019

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Graphene oxide (GO) holds high promise for diagnostic and therapeutic applications in nanomedicine but reportedly displays immunotoxicity, underlining the need for developing functionalized GO with improved biocompatibility. This study describes adverse effects of GO and amino‐functionalized GO (GONH2) during Caenorhabditis elegans development and ageing upon acute or chronic exposure. Chronic GO treatment throughout the C. elegans development causes decreased fecundity and a reduction of animal size, while acute treatment does not lead to any measurable physiological decline. However, RNA‐Sequencing data reveal that acute GO exposure induces innate immune gene expression. The p38 MAP kinase, PMK‐1, which is a well‐established master regulator of innate immunity, protects C. elegans from chronic GO toxicity, as pmk‐1 mutants show reduced tissue‐functionality and facultative vivipary. In a direct comparison, GONH2 exposure does not cause detrimental effects in the wild type or in pmk‐1 mutants, and the innate immune response is considerably less pronounced. This work establishes enhanced biocompatibility of amino‐functionalized GO in a whole‐organism, emphasizing its potential as a biomedical nanomaterial.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Improved Biocompatibility of Amino‐Functionalized Graphene Oxide in Caenorhabditis elegans

Rive

Reina

Wagle

et al. 2019

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“…[6,7] Indeed, primary human neutrophils sense GO in as ize-dependent manner and release so called neutrophil extracellular traps or NETs leading to degradation of the offending material. [6][7][8] Biomedical applications of GO have been more widely explored, [3] but some recent studies have shown promising results also for graphene.For example, we discovered that FLG dispersions displayed specific killing action on monocytes,s howing neither toxic nor activation effects on the other immunocompetent cells.T he unique ability of FLG to specifically trigger necrosis of monocytic cells,m ight be exploited to treat aggressive forms of myelomonocytic leukemia. [9] Recent results also proved that graphene can be exploited in neural interfaces and flexible devices.…”

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confidence: 99%

“…[6] Then, we wanted to assess if hMPO-rich human neutrophils were able to biodegrade FLG and SLG.O ur previous work have demonstrated that neutrophils are capable to degrade GO and CNTs extracellularly upon degranulation of oxidative enzymes. [7,8,18] TheN-formyl-methionyl-leucyl-phenylalanine (fMLP) tripeptide is ap otent activator of neutrophils and cytochalasin B(Cyto-B) enhances several fMLPstimulated neutrophil responses,i ncluding aggregation, superoxide production, and degranulation. [19] Freshly isolated primary human neutrophils were activated with fMLP and Cyto-B and incubated with FLG and SLG.N eutrophils activated in this manner were added every day up to five days ( Figure 4A).…”

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confidence: 99%

Degradation of Single‐Layer and Few‐Layer Graphene by Neutrophil Myeloperoxidase

et al. 2018

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Biodegradability of graphene is one of the fundamental parameters determining the fate of this material in vivo. Two types of aqueous dispersible graphene, corresponding to single-layer (SLG) and few-layer graphene (FLG), devoid of either chemical functionalization or stabilizing surfactants, were subjected to biodegradation by human myeloperoxidase (hMPO) mediated catalysis. Graphene biodegradation was also studied in the presence of activated, degranulating human neutrophils. The degradation of both FLG and SLG sheets was confirmed by Raman spectroscopy and electron microscopy analyses, leading to the conclusion that highly dispersed pristine graphene is not biopersistent.

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“…GO was produced in house following the modified Hummer's method as previously described [13][14] . Full characterization of the material has been provided in a previous study 15 where it was termed small GO (s-GO) in order to differentiate it from larger counterparts that have not been used in the present study, and is summarized in Table S1. In brief, average lateral size of the material used here was 1 µm and thickness corresponded to 1 to 2 layers of GO (1-2 nm).…”

Section: Methodsmentioning

confidence: 99%

Graphene Oxide as 2D Platform for Complexation and Intracellular Delivery of siRNA

Lázaro

Vranic

Rodrigues

et al. 2018

Preprint

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The development of efficient and safe nucleic acid delivery vectors remains an unmet need holding back translation of gene therapy approaches into bedside. Graphene oxide (GO) could help bypass such bottleneck thanks to its large surface area, versatile chemistry and biocompatibility, which could overall enhance transfection efficiency while abolishing some of the limitations linked to the use of viral vectors. Here, we aimed to assess the capacity of bare GO, without any further surface modification, to complex a short double-stranded nucleic acid of biological relevance (siRNA) and mediate its intracellular delivery. GO formed stable complexes with siRNA at 10:1, 20:1 and 50:1 GO:siRNA mass ratios. Complexation was further corroborated by atomistic molecular dynamics simulations. GO:siRNA complexes were promptly internalized in a primary mouse cell culture, as early as 4 h after exposure. At this time point, intracellular siRNA levels were comparable to those provided by a lipid-based transfection reagent that achieved significant gene silencing. Time-lapse tracking of internalized GO and siRNA evidenced a sharp decrease of intracellular siRNA from 4 to 12 h, while GO was sequestered in large vesicles, which may explain the lack of biological effect (i.e. gene silencing) achieved by GO:siRNA complexes. This study underlines the potential of non-surface modified GO flakes to act as 2D siRNA delivery platforms, without the need for cationic functionalization, but warrants further vector optimization to allow effective release of the nucleic acid and achieve efficient gene silencing.

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Graphene Oxide Elicits Membrane Lipid Changes and Neutrophil Extracellular Trap Formation

Cited by 71 publications

References 87 publications

Improved Biocompatibility of Amino‐Functionalized Graphene Oxide in Caenorhabditis elegans

Improved Biocompatibility of Amino‐Functionalized Graphene Oxide in Caenorhabditis elegans

Degradation of Single‐Layer and Few‐Layer Graphene by Neutrophil Myeloperoxidase

Graphene Oxide as 2D Platform for Complexation and Intracellular Delivery of siRNA

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