Understanding the hemotoxicity of graphene nanomaterials through their interactions with blood proteins and cells

Kenry, Kenry

doi:10.1557/jmr.2017.388

Cited by 21 publications

(14 citation statements)

References 70 publications

(89 reference statements)

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“…The effects of GOs on the biocompatibility/toxicity of immune cells are now considered. The interactions of GOs with the immune and circulatory systems are crucial; once administrated, they directly come in contact with such systems [ 107 , 108 ]. Macrophages are the cells involved in the defense mechanism of innate immune system and provide a first line of defense against microorganisms.…”

Section: Cell Viability and Toxicitymentioning

confidence: 99%

Graphene Nanomaterials: Synthesis, Biocompatibility, and Cytotoxicity

Liao

Tjong

2018

IJMS

373

272

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Graphene, graphene oxide, and reduced graphene oxide have been widely considered as promising candidates for industrial and biomedical applications due to their exceptionally high mechanical stiffness and strength, excellent electrical conductivity, high optical transparency, and good biocompatibility. In this article, we reviewed several techniques that are available for the synthesis of graphene-based nanomaterials, and discussed the biocompatibility and toxicity of such nanomaterials upon exposure to mammalian cells under in vitro and in vivo conditions. Various synthesis strategies have been developed for their fabrication, generating graphene nanomaterials with different chemical and physical properties. As such, their interactions with cells and organs are altered accordingly. Conflicting results relating biocompatibility and cytotoxicity induced by graphene nanomaterials have been reported in the literature. In particular, graphene nanomaterials that are used for in vitro cell culture and in vivo animal models may contain toxic chemical residuals, thereby interfering graphene-cell interactions and complicating interpretation of experimental results. Synthesized techniques, such as liquid phase exfoliation and wet chemical oxidation, often required toxic organic solvents, surfactants, strong acids, and oxidants for exfoliating graphite flakes. Those organic molecules and inorganic impurities that are retained in final graphene products can interact with biological cells and tissues, inducing toxicity or causing cell death eventually. The residual contaminants can cause a higher risk of graphene-induced toxicity in biological cells. This adverse effect may be partly responsible for the discrepancies between various studies in the literature.

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Section: Cell Viability and Toxicitymentioning

confidence: 99%

Graphene Nanomaterials: Synthesis, Biocompatibility, and Cytotoxicity

Liao

Tjong

2018

IJMS

373

272

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“…Toxicity of GO is largely dependent on intrinsic physicochemical properties including lateral size, thickness, number of layers, surface properties, and methods of the synthesis, in addition to the dose, time of exposure, cell type, and administration method [11][12][13][14]. Among these factors, surface properties (e.g., functional groups, charge, carbon/oxygen ratio, and hydrophobicity) are crucial in determining the nature of the interaction between GO and biomolecules [15].…”

Section: Advances In Condensed Matter Physicsmentioning

confidence: 99%

Cytotoxicity Evaluation of Ammonia-Modified Graphene Oxide Particles in Lung Cancer Cells and Embryonic Stem Cells

Keremidarska-Markova

Hristova-Panusheva

Andreeva

et al. 2018

Advances in Condensed Matter Physics

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Potential toxicity of graphene oxide (GO) is a subject of increasing research interest in the recent years. Here, we have evaluated the cytotoxicity of ammonia-modified GO (GO-NH2) and pristine GO particles in human lung cancer cells, A549 and embryonic stem cells, Lep3 exposed to different particles concentrations (0.1, 1, 10, 20, and 50 μg/ml) for different times (24 and 48h). Compared with GO, GO-NH2 particles possessed smaller size, positive surface charge and higher thickness. An increased propensity to aggregation in cell cultures was also found for GO-NH2 particles. Cytotoxicity evaluation revealed that GO-NH2 particles are more toxic than pristine GO. Applied at concentrations of 10, 20 and 50 μg/ml for 24h they affect significantly cell morphology of viable embryonic stem cells whereas human lung cancer A549 cells seem to be relatively more resistant to short-time exposure. After 48h exposure however cell proliferation of A549 cells was strongly suppressed in a dose-dependent manner while the proliferation ability of embryonic stem cells was not affected. These results suggested that both GO particles exert different degree of cytotoxicity which is time, dose and cell dependent. In general, ammonia-modified GO particles are more toxic than the pristine GO which should be taken into account for future biomedical applications.

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“…Although GO has been shown to cause the rupture of cell membrane, the magnitude of decrease in cell viability does not exceed 20% for 24 h or even longer time when the concentration of GO is < 100 μg mL −1 (Liao et al, 2011; Fiorillo et al, 2015). Additionally, the cytotoxicity of GO is highly diminished after capping with biopolymers, such as proteins, oligonucleotide, and polysaccharide (Chong et al, 2015; Rezaei et al, 2016; Kenry, 2018; Liu et al, 2018; Ren et al, 2018). In this study, we used MTT assay to evaluate the cytotoxicity of Supra-TBA 15/29 -GO toward different mammalian cells (Figure S11A, Supporting Information).…”

Section: Resultsmentioning

confidence: 99%

Supramolecular Aptamers on Graphene Oxide for Efficient Inhibition of Thrombin Activity

et al. 2019

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Graphene oxide (GO), a two-dimensional material with a high aspect ratio and polar functional groups, can physically adsorb single-strand DNA through different types of interactions, such as hydrogen bonding and π-π stacking, making it an attractive nanocarrier for nucleic acids. In this work, we demonstrate a strategy to target exosites I and II of thrombin simultaneously by using programmed hybrid-aptamers for enhanced anticoagulation efficiency and stability. The targeting ligand is denoted as Supra-TBA 15/29 (supramolecular TBA 15/29 ), containing TBA 15 (a 15-base nucleotide, targeting exosite I of thrombin) and TBA 29 (a 29-base nucleotide, targeting exosite II of thrombin), and it is designed to allow consecutive hybridization of TBA 15 and TBA 29 to form a network of TBAs (i.e., supra-TBA 15/29 ). The programmed hybrid-aptamers (Supra-TBA 15/29 ) were self-assembled on GO to further boost anticoagulation activity by inhibiting thrombin activity, and thus suppress the thrombin-induced fibrin formation from fibrinogen. The Supra-TBA 15/29 -GO composite was formed mainly through multivalent interaction between poly(adenine) from Supra-TBA 15/29 and GO. We controlled the assembly of Supra-TBA 15/29 on GO by regulating the preparation temperature and the concentration ratio of Supra-TBA 15/29 to GO to optimize the distance between TBA 15 and TBA 29 units, aptamer density, and aptamer orientation on the GO surfaces. The dose-dependent thrombin clotting time (TCT) delay caused by Supra-TBA 15/29 -GO was >10 times longer than that of common anticoagulant drugs including heparin, argatroban, hirudin, and warfarin. Supra-TBA 15/29 -GO exhibits high biocompatibility, which has been proved by in vitro cytotoxicity and hemolysis assays. In addition, the thromboelastography of whole-blood coagulation and rat-tail bleeding assays indicate the anticoagulation ability of Supra-TBA 15/29 -GO is superior to the most widely used anticoagulant (heparin). Our highly biocompatible Supra-TBA 15/29 -GO with strong multivalent interaction with thrombin [dissociation constant ( K d ) = 1.9 × 10 −11 M] shows great potential as an effective direct thrombin inhibitor for the treatment of hemostatic disorders.

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Understanding the hemotoxicity of graphene nanomaterials through their interactions with blood proteins and cells

Cited by 21 publications

References 70 publications

Graphene Nanomaterials: Synthesis, Biocompatibility, and Cytotoxicity

Graphene Nanomaterials: Synthesis, Biocompatibility, and Cytotoxicity

Cytotoxicity Evaluation of Ammonia-Modified Graphene Oxide Particles in Lung Cancer Cells and Embryonic Stem Cells

Supramolecular Aptamers on Graphene Oxide for Efficient Inhibition of Thrombin Activity

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