Protein corona reduced graphene oxide cytotoxicity by inhibiting endocytosis

Yang, Ying; Han, Panli; Xie, Xuejie; Yin, Xiuhua; Duan, Guangxin; Wen, Ling

doi:10.1016/j.colcom.2021.100514

Cited by 12 publications

(12 citation statements)

References 29 publications

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“…The present results showed that Ti 3 C 2 T x nanosheets show a very weak capacity to cause the generation of extra intracellular ROS as compared with the control group even when the treatment concentration was increased to 200 μg/mL (Figure a,b). By contrast, GO nanosheets indeed provoked the generation of high-level ROS (Figure a,b), which agreed very well with previous literature. ,, In specific, the intracellular ROS level induced by GO nanosheets was about 2-fold that induced by the control and Ti 3 C 2 T x nanosheets at a concentration of 200 μg/mL and duration of 48 h ( p < 0.01; Figure b). These results were further validated by the fluorescence microscope observations (Figure c, top and middle panels).…”

Section: Resultssupporting

confidence: 91%

“…In addition, GO nanosheets exhibited a relatively strong capability of damaging the integrity of cell membranes. Next, the intracellular reactive oxygen species (ROS) levels were detected because of their importance in inducing cytotoxicity by many nanomaterials. , Excessive production of ROS can induce cell damage via various mechanisms, such as interacting with and destroying cellular proteins, DNA, and lipids or affecting normal cellular signaling pathways, the integrity of the mitochondrial inner membrane, and gene regulation. The present results showed that Ti 3 C 2 T x nanosheets show a very weak capacity to cause the generation of extra intracellular ROS as compared with the control group even when the treatment concentration was increased to 200 μg/mL (Figure a,b).…”

Section: Resultsmentioning

confidence: 99%

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Cytocompatibility of Ti₃C₂T_x MXene with Red Blood Cells and Human Umbilical Vein Endothelial Cells and the Underlying Mechanisms

Huang

Hou

et al. 2023

Chem. Res. Toxicol.

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Two-dimensional (2D) nanomaterials have been widely used in biomedical applications because of their biocompatibility. Considering the high risk of exposure of the circulatory system to Ti3C2T x , we studied the cytocompatibility of Ti3C2T x MXene with red blood cells (RBCs) and human umbilical vein endothelial cells (HUVECs) and showed that Ti3C2T x had excellent compatibility with the two cell lines. Ti3C2T x at a concentration as high as 200 μg/mL caused a negligible percent hemolysis of 0.8%. By contrast, at the same treatment concentration, graphene oxide (GO) caused a high percent hemolysis of 50.8%. Scanning electron microscopy revealed that RBC structures remained intact in the Ti3C2T x treatment group, whereas those in the GO group completely deformed, sunk, and shrunk, which resulted in the release of cell contents. This difference can be largely ascribed to the distinct surficial properties of the two nanosheets. In specific, the fully covered surface-terminating −O and −OH groups leading to Ti3C2T x had a very hydrophilic surface, thereby hindering its penetration into the highly hydrophobic interior of the cell membrane. However, the strong direct van der Waals attractions coordinated with hydrophobic interactions between the unoxidized regions of GO and the lipid hydrophobic tails can still damage the integrity of the cell membranes. In addition, the sharp and keen-edged corners of GO may also facilitate its relatively strong cell membrane damage effects than Ti3C2T x . Thus, the excellent cell membrane compatibility of Ti3C2T x nanosheets and their ultraweak capacity to provoke excessive ROS generation endowed them with much better compatibility with HUVECs than GO nanosheets. These results indicate that Ti3C2T x has much better cytocompatibility than GO and provide a valuable reference for the future biomedical applications of Ti3C2T x .

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Section: Resultssupporting

confidence: 91%

Section: Resultsmentioning

confidence: 99%

Cytocompatibility of Ti₃C₂T_x MXene with Red Blood Cells and Human Umbilical Vein Endothelial Cells and the Underlying Mechanisms

Huang

Hou

et al. 2023

Chem. Res. Toxicol.

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“…Results displayed in Fig. 2 are in line with previous findings [27,28] and suggest that the anti-cancer effect of GO may be drastically impaired in a protein-enriched physiological environment likely due to the reduction in cell penetration. This phenomenon has been studied for a wide variety of nanoparticles and cell systems [29].…”

Section: Resultssupporting

confidence: 90%

The protein corona reduces the anticancer effect of graphene oxide in HER-2-positive cancer cells

et al. 2022

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“…A549 cells grow in a different culture medium than NHBE cells, which includes 10% fetal bovine serum (FBS). Previous research has shown that the presence of FBS in the medium can reduce graphene-induced cytotoxicity 43 . Therefore, to evaluate the possible effect of FBS, apoptosis and necrosis were assessed in A549 cells grown in the FBS-free medium for 6 and 24 h and exposed to 5 µg/mL GO, FLG, and sFLG for 24 h (Supplementary Fig.…”

Section: Resultsmentioning

confidence: 99%

“…3 ), showed different behaviour in response to GRMs. This effect could be enhanced by differences in the composition of the culture media of both models, especially by the presence of FBS in the culture medium of A549 cells, which may be associated with a higher protein corona in the graphene, therefore lower cytotoxicity 43 . Although the medium of NHBE cells lacks FBS, it incorporates high concentrations of different protein complements, producing the protein corona.…”

Section: Discussionmentioning

confidence: 99%

Rapid and efficient testing of the toxicity of graphene-related materials in primary human lung cells

Frontiñán-Rubio

González

Vázquez

et al. 2022

Sci Rep

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Graphene and its derivative materials are manufactured by numerous companies and research laboratories, during which processes they can come into contact with their handlers' physiological barriers—for instance, their respiratory system. Despite their potential toxicity, these materials have even been used in face masks to prevent COVID-19 transmission. The increasingly widespread use of these materials requires the design and implementation of appropriate, versatile, and accurate toxicological screening methods to guarantee their safety. Murine models are adequate, though limited when exploring different doses and lengths of exposure—as this increases the number of animals required, contrary to the Three R's principle in animal experimentation. This article proposes an in vitro model using primary, non-transformed normal human bronchial epithelial (NHBE) cells as an alternative to the most widely used model to date, the human lung tumor cell line A549. The model has been tested with three graphene derivatives—graphene oxide (GO), few-layer graphene (FLG), and small FLG (sFLG). We observed a cytotoxic effect (necrosis and apoptosis) at early (6- and 24-h) exposures, which intensified after seven days of contact between cells and the graphene-related materials (GRMs)—with cell death reaching 90% after a 5 µg/mL dose. A549 cells are more resistant to necrosis and apoptosis, yielding values less than half of NHBE cells at low concentrations of GRMs (between 0.05 and 5 µg/mL). Indeed, GRM-induced cell death in NHBE cells is comparable to that induced by toxic compounds such as diesel exhaust particles on the same cell line. We propose NHBE as a suitable model to test GRM-induced toxicity, allowing refinement of the dose concentrations and exposure timings for better-designed in vivo mouse assays.

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Protein corona reduced graphene oxide cytotoxicity by inhibiting endocytosis

Cited by 12 publications

References 29 publications

Cytocompatibility of Ti₃C₂T_x MXene with Red Blood Cells and Human Umbilical Vein Endothelial Cells and the Underlying Mechanisms

Cytocompatibility of Ti₃C₂T_x MXene with Red Blood Cells and Human Umbilical Vein Endothelial Cells and the Underlying Mechanisms

The protein corona reduces the anticancer effect of graphene oxide in HER-2-positive cancer cells

Rapid and efficient testing of the toxicity of graphene-related materials in primary human lung cells

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Protein corona reduced graphene oxide cytotoxicity by inhibiting endocytosis

Cited by 12 publications

References 29 publications

Cytocompatibility of Ti3C2Tx MXene with Red Blood Cells and Human Umbilical Vein Endothelial Cells and the Underlying Mechanisms

Cytocompatibility of Ti3C2Tx MXene with Red Blood Cells and Human Umbilical Vein Endothelial Cells and the Underlying Mechanisms

The protein corona reduces the anticancer effect of graphene oxide in HER-2-positive cancer cells

Rapid and efficient testing of the toxicity of graphene-related materials in primary human lung cells

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Product

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Cytocompatibility of Ti₃C₂T_x MXene with Red Blood Cells and Human Umbilical Vein Endothelial Cells and the Underlying Mechanisms

Cytocompatibility of Ti₃C₂T_x MXene with Red Blood Cells and Human Umbilical Vein Endothelial Cells and the Underlying Mechanisms