. 2018 May 21;10(3):53. doi: 10.1007/s40820-018-0206-4

Table 5.

GBNs toxicity effects in various cells (data adapted from Ref. [152]).

GBNs [Exposure conditions]	Cell types	Effects	Refs.
Pristine graphene [20 µg mL⁻¹ for 24 h]	Peritoneal macrophages; RAW264.7	Elevated transcription and secretion of cytokines and chemokines, which is triggered by activation of the NF-κB signaling pathway	[251]
Pristine graphene [0-80 µg mL⁻¹ for 24 and 48 h]	RAW264.7	Induction of cytotoxicity through the depletion of the mitochondrial membrane potential and the increase in intracellular reactive oxygen species, then trigger apoptosis by activation of the mitochondrial pathway	[252]
Pristine graphene; functionalized graphene [75 g mL⁻¹ for 24 or 48 h]	RAW264.7	High intracellular uptake of functionalized, hydrophilic graphene compared to the hydrophobic pristine graphene	[253]
Graphene; few-layer graphene (FLG) microsheets [5 h for macrophages and 24 h for other cell types]	Primary human keratinocytes; human lung epithelial cells; Murine macrophages	GBNs enter cells through spontaneous membrane penetration at edge asperities and corner sites	[254]
Graphene [N/A]	HeLa; Panc-1	The cellular responses are strongly dependent on either cell type or hard corona composition	[255]
Graphene quantum dots (GQDs) [0–200 μg mL⁻¹, for 24, 48 or 72 h]	THP-1	Induction of inflammatory response, apoptosis and autophagy in macrophages via p38 MAPK and NF-κB signaling pathways	[256]
Pluronic dispersed graphene; GO (graphene oxide) [administered directly into the lungs of mice]	Lung cells	Increased rate of mitochondrial respiration and the generation of reactive oxygen species, activating inflammatory and apoptotic pathways	[257]
Graphene, GO [20 μg mL⁻¹; 24 h]	MDA-MB-231; B16F10	Inhibits the migration and invasion of various cancer cells by inhibiting the activities of ETC complexes	[258]
Carboxyl graphene nanoplatelets (CXYG) [0–32 μg mL⁻¹ for 72 h]	HepG2	Cytotoxicity in HepG2 cells with plasma membrane damage and induction of oxidative stress	[259]
GO [1–200 mg L⁻¹, 24 h]	HepG2	NADPH oxidase-dependent ROS formation; deregulation of antioxidant/DNA repair/apoptosis-related genes	[260]
GO [100 mg L⁻¹ for 48 h]	GLC-82	Alters the miRNA expression profile	[261]
GO [0–16 μg mL⁻¹ for 72 h]	HepG2	Caused cytotoxicity in HepG2 cells with plasma membrane damage and induction of oxidative stress	[259]
GO [N/A]	RAW-264.7; Saos-2; 3T3	Impact on cytoskeleton; alterations in cell cycle	[262]
GO and its nanoassemblies [l μg mL⁻¹; 24–72 h]	Mouse embryonic fibroblast (MEF)	Without induction of noticeable harmful effects	[263]
GO, bGO, pGO-5, pGO-30 and GS (graphene sheets) [0–200 μg mL⁻¹, for 3 or 24 h]	Red blood cells; human skin fibroblasts	All the GO and GS show dose-dependent hemolytic activity on RBCs	[264]
GO [50 μg mL⁻¹ for 24 h]	MEF	Higher degree of cytotoxicity and apoptosis.	[265]
GO [0–100 μg mL⁻¹ 0–5 days]	Human fibroblast cell	Dose- and time-dependent cytotoxicity, decreasing cell adhesion, inducing cell floating and apoptosis	[266]
GO [N/A]	Red blood cells	Strong hemolytic activity	[267]
GO [20–100 μg mL⁻¹ for 0–12 h]	A549	Cytotoxicity of GO is largely attenuated due to the extremely high protein adsorption ability of GO	[268]
GO [0–20 μg mL⁻¹]	Peritoneal macrophage; J774A.1; LLC; MCF-7; HepG2; human umbilical vein endothelial cells (HUVEC)	Microsized GO induced much stronger inflammation responses, while nanosized graphene sheet showed better biocompatibility	[269]
GO [5–100 μg mL⁻¹ for 24 h]	RAW264.7	Provoked the Toll-like receptor (TLR) signaling cascades and triggered ensuing cytokine responses	[269]
GO [20 μg mL⁻¹ for 24 h]	J774A.1; RAW 264.7	Activation of TLR4 signaling leads to GO-mediated macrophagic necrosis	[270]
GO [1–100 μg mL⁻¹ for 24 h]	Human monocyte-derived macrophages; peritoneal macrophages	Significant impact on cellular viability, ROS generation and cellular activation	[271]
GO, PVP-GO [25–100 μg mL⁻¹ for 48 h]	Dendritic cells	PVP-modified GO has a low immunogenicity than unadorned GO	[272]
GO, TiO₂-GO [100 and 300 μg mL⁻¹ for 4 h]	A549	GO enters A549 cells and locates in the cytoplasm and nucleus without causing any cell damage. The TiO₂–GO composite separated into GO and TiO₂ after TiO₂–GO composite entered A549 cells	[273]
GO, sGO [12.5 μg mL⁻¹ for 48 h]	PC-12	Inhibit Aβ peptide monomer fibrillation and clear mature amyloid fibrils	[274]
GO flake [10 μg mL⁻¹]	Mesenchymal stem cells (MSC)	GO flakes effectively prevent a series of adverse cell signaling cascades that result in the anoikis of MSCs in response to ROS	[275]
GO [37.5 μg mL⁻¹ FITC-PEG-GOs for 2 h]	Saos-2; HepG2; RAW-264.7	Processes such as micropinocytosis, microtubule-dependent mechanisms, clathrin-dependent mechanisms and phagocytosis are involved	[276]
GO [20–50 μg mL⁻¹ for 30 min–14 h]	C2C12	Cells enter through clathrin-mediated endocytosis, and the increase in graphene size enhances phagocytotic uptake of the nanosheets	[277]
GO [40 or 80 μg mL⁻¹ for 24 h]	MDA-MB-231; MDA-MB-436; SK-BR-3	PEG-GO inhibited the migratory and invasive properties of human metastatic breast cancer cell lines by inhibiting ATP synthesis, leading to a disruption of F-actin cytoskeletal assembly	[278]
NGO [N/A]	HCT-116	No apparent toxicity as drug carrier	[279]
NGO [N/A]	HeLa	No apparent toxicity as drug carrier	[280]
Oxidized graphene nanoribbons (O-GNR) [10–400 μg mL⁻¹ for 12–48 h]	HeLa; NIH-3T3; SKBR3; MCF-7	Dose-dependent and time-dependent cytotoxic effects on the four cell lines	[281]
O-GNR [50 μg mL⁻¹ for 30 min]	MCF-7; A549; MRC5	Significant O-GNR-PEG-DSPE uptake into cells with high EGFR expression	[282]
O-GNR [N/A]	U251; CG-4; MCF-7	No apparent toxicity as drug carrier	[50]
O-GNR [0–100 μg mL⁻¹ for 24 h]	A549	GONRs with concentrations ≤ 50 μg/mL showed no significant cytotoxicity; GONRs with a concentration of 100 μg/mL exhibited significant cytotoxicity and resulted in a decrease in cell growth and induction of cell apoptosis	[283]
O-GNR, GNO and GONP [0–300 μg mL⁻¹ 24–72 h]	MSC	GNOs, GONRs and GONPs at concentrations of less than 50 μg/mL for 24 or 72 h could be considered potentially safe incubation conditions for ex vivo labeling for MSCs	[284]
GO; RGO [200 μg mL⁻¹ 24 h]	A549	Protein-coated graphene resulted in a markedly less cytotoxicity than uncoated graphene	[285]
GO, RGO [10 μg mL⁻¹]	HUVEC	Significant increase in both intercellular ROS levels and mRNA levels of HO1 and TrxR. Moreover, a significant amount of DNA damage is observed in GO-treated cells, but not in RGO-treated cells	[286]
GO, RGO [0.0125–12.5 μg cm⁻² for 5 days]	A549; RAW 264.7	Lower concentrations of GO/RGO did not lead to an increase in ROS production. Cellular internalization of GO was observed in phago(endo)somes without signs of any intracellular damage.	[287]
RGO/HARGO (hyaluronic acid GO) [20 μg mL⁻¹ for 24 h]	KB	No significant cell death observed in the absence of NIR irradiation	[288]
RGO [N/A]	Ramos; CCRF-CEM	No apparent toxicity as drug carrier	[289]
RGO [1–200 mg L⁻¹ for 24 h]	HepG2	Hydrophobic RGO was found to mostly adsorbed at cell surface without internalization, ROS generation by physical interaction, poor gene regulation	[260]
RGO [1–100 μg mL⁻¹ 24 h]	Human blood cells; HUVEC	The biocompatible biopolymer-functionalized RGO exhibited excellent biocompatibility	[290]
RGO, GONP, RGONP [0.01–100 μg mL⁻¹ for 24 h]	MSC	The RGONPs exhibited a strong potential in destruction of the cells with the threshold concentration of 1.0 mg/mL, while the cytotoxicity of the RGO sheets appeared at high concentration of 100 mg/mL after 1 h	[291]
GO, RGO [1–10 μg mL⁻¹ for 24 or 48 h]	HUVEC	GO exhibits higher toxicity than RGO due to ROS generation. Small flake size graphene exhibits greater cytotoxicity compared to larger sheets due to intracellular accumulation of graphene	[286]
GO, RGO [0–20 μg mL⁻¹]	Human platelets	GO can evoke strong aggregatory response in platelets comparable to that elicited by thrombin	[292]
GO, RGO, G-NH₂ [2–10 μg mL⁻¹ for 3 h]	Red blood cells	G-NH₂ is not endowed with thrombotoxic property	[293]
GO, RGO [100 μg mL⁻¹]	U87 U118	Reduction in cell viability and proliferation and induced apoptosis	[294]
RGO [50 μg mL⁻¹]	U87	Reduction in GBM tumor volume was observed. RGO + Arg shows antiangiogenic and proapoptotic characteristics	[295]

The numbers in the parentheses are respective references