Graphene Nanomaterials: Synthesis, Biocompatibility, and Cytotoxicity
Abstract
:1. Introduction
2. Synthesis of Graphene-Based Nanomaterials
2.1. Epitaxial Graphene on SiC Wafers
2.2. Chemical Vapor Deposited Graphene Films
2.3. Liquid Phase Exfoliation
2.4. Chemical and Thermal Reduction of GO
2.5. Graphene-Polymer Nanocomposites
3. Cell Viability and Toxicity
3.1. In Vitro Cell Cultivation
3.1.1. CVD-Grown Graphene
3.1.2. Graphene Oxide and Its Derivatives
Graphene Oxide
PEGylation
Reduced Graphene Oxide
3.2. In Vivo Animal Model
4. GO-Polymer Nanocomposites
5. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
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Material | Lateral Size, nm | Cell Type | Concentration and Exposure Time | Cytotoxic Effect | Ref. |
---|---|---|---|---|---|
CVD-graphene | Thickness: 3–5 layers | PC12 | 0.01, 0.1, 1, 10 and 100 µg/mL for 1–24 h | Apoptosis at ≥10 µg/mL | [89] |
GO | 200–700 | RAW 264.7 | 1, 10, 50 and 200 µg/mL for 6 and 24 h | Apoptosis by membrane pores at ≥10 µg/mL | [84] |
GO | 200–700 | A549 | 1, 10, 50 and 200 µg/mL for 6 and 24 h | Dose dependent toxicity. Cell death at ≥50 µg/mL | [84] |
GO | 979 | Human Skin Keratinocyte | 0.4, 1.2, 3.7, 11.1, 33.3 and 100 µg/mL for 3–72 h | Dose- and time-dependent ROS production | [88] |
GO | 342–765 | Human Erythrocyte | 3.125, 6.25, 12.5, 25, 50, 100 and 200 µg/mL for 3 h | Dose- and size-dependent hemolysis | [45] |
GO | 385 | HepG2 | 1,2, 4, 8 and 16 µg/mL for 72 h | Plasma membrane damage at 4 µg/mL | [43] |
GO | 440–670 | Swine Spermatozoa | 0.5, 1, 5, 10 and 50 µg/mL for 1 to 4 h | Dose dependent toxicity. Cell death at ≥10 µg/mL | [82] |
GO | --- | hCorECs; hConECs | 12.5, 25, 50 and 100 µg/mL for 2 h and 24 h | Apoptosis at ≥50 µg/mL | [113] |
GO | 201 | Murine Macrophage | 1, 2, 4, 10, 20, 50 and 100 µg/mL for 24 h | Cell membrane damage at ≥10 µg/mL | [119] |
GO-PEG | 10–120 | Saos-2; MC3T3-E1; RAW-264.7 | 75 µg/mL for 24 h | GO-PEG accumulated on F-actin; ROS formation | [116] |
GO-PEG | 200 | Murine Macrophage | 10 and 40 µg/mL for 6, 12, 24 and 48 h | Inflammation response by secreting cytokine | [118] |
GO-PAM | 363 | Murine Macrophage | 1, 2, 4, 10, 20, 50 and 100 µg/mL for 24 h | Cell membrane damage at ≥10 µg/mL | [119] |
rGO-PEG | 910 | Murine Astrocyte | 10 and 100 µg/mL | Excess ROS and cell death at 100 µg/mL | [117] |
rGO; rGO-PEG | --- | A549 | 1–200 µg/mL | Dose dependent toxicity. Apoptosis at ≥25 µg/mL | [121] |
Green rGO | 65–90 | Human Lymphocyte | 50, 100 and 250 µg/mL | Loss of lysosomal integrity at ≥100 µg/mL | [105] |
rGO | 11 | hMSCS | 0.1 µg/mL | DNA fragmentation and chromosomal aberration | [122] |
GO; rGO | 400–800 | HUVEC | 10 µg/mL | GO induced more ROS, HO1 and TrxR levels, and DNA damage than rGO | [126] |
hGO; rGO | 105–150 | BEAS-2B; THP-1 | 25, 50, 100 and 200 µg/mL for 24 h | hGO induced toxicity due to lipid peroxidation. rGO had little effect on cell viability | [87] |
hGO; rGO | 105–150 | Murine Erythrocyte | 25, 50, 100 and 200 µg/mL | rGO and hGO showed negligible and high rates of hemolysis respectively | [87] |
TRG | --- | Monkey Vero | 10, 50, 100 and 300 µg/mL for 24 h | Apoptosis at >100 µg/mL | [127] |
Material | Animal Model | Dosage | Administration Process | Biological Effect | Ref. |
---|---|---|---|---|---|
GO | Balb/c mice | 4 mg/kg | Oral feeding and i.p. injection | Insignificant toxicity in mice | [128] |
GO | Mice | 50 µg/mouse | Intraperitoneal injection | No acute and chronic inflammation after intraperitoneal injection | [129] |
GO | Rabbits | 100–300 μg/eye | Intravitreal injection | No change in eyeball appearance and intraocular pressure | [130] |
GO-PEG | Balb/c mice | 20 mg/kg | Intravenous injection | low uptake by RES; no sign of toxicity on spleen and liver | [48] |
GO-NH2 | Mice | 250 μg/kg | Intravenous injection | No pulmonary thromboembolism | [131] |
GO | KM mice | 0.1, 0.25 and 0.4 mg per mouse | Intravenous injection | GOs found in the lung, liver and spleen; Dose-dependent lung inflammation and granuloma | [47] |
hGO; GO | B6 mice | 2 mg/kg | Oropharyngeal aspiration | Hydrated GOs induced more serious lung inflammation & lipid peroxidation in alveolar macrophages than GOs | [87] |
GO | Balb/c mice | 4 mg/kg | Intraperitoneal injection | GOs induced brain and kidney damages by increasing ROS and MDA, but decreasing glutathione levels | [23] |
GO | Balb/c mice | 5 mg/kg | Intravenous & intratracheal administration | Large GOs (750–1300 nm) induced very high pulmonary and systemic inflammatory cytokine production and inflammatory cell recruitment | [110] |
GO | KM mice | 10 mg/kg | Intratracheal instillation | GOs mainly retained in the lung. Acute lung injury and chronic pulmonary fibrosis. | [133] |
GO | Mice | 10 mg/kg | Intravenous injection | Inflammation cell infiltration, pulmonary edema and granuloma formation in the lung | [134] |
GO | Wistar rat | 50, 150, or 500 mg/kg | Intraperitoneal injection | Granulomatous reaction with giant cell formation; neuronal degeneration and necrosis | [135] |
rGO | Wistar rat | 7 mg/kg | Intravenous injection | rGO entered hippocampus & thalamus, reduced paracellular tightness of BBB | [137] |
rGO-PEG | Wistar rat | 7 mg/kg | Intravenous injection | rGO-PEG reduced blood-brain barrier function due to ROS and lipid peroxidation generation | [117] |
rGO-PEG | Albino mice | 10 mg/kg | Intravenous and i.p. injections | rGO-PEG distributes in liver, kidney bone marrow, spleen and brain | [136] |
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Liao, C.; Li, Y.; Tjong, S.C. Graphene Nanomaterials: Synthesis, Biocompatibility, and Cytotoxicity. Int. J. Mol. Sci. 2018, 19, 3564. https://doi.org/10.3390/ijms19113564
Liao C, Li Y, Tjong SC. Graphene Nanomaterials: Synthesis, Biocompatibility, and Cytotoxicity. International Journal of Molecular Sciences. 2018; 19(11):3564. https://doi.org/10.3390/ijms19113564
Chicago/Turabian StyleLiao, Chengzhu, Yuchao Li, and Sie Chin Tjong. 2018. "Graphene Nanomaterials: Synthesis, Biocompatibility, and Cytotoxicity" International Journal of Molecular Sciences 19, no. 11: 3564. https://doi.org/10.3390/ijms19113564