Structure–Activity Relationship of Graphene-Based Materials: Impact of the Surface Chemistry, Surface Specific Area and Lateral Size on Their In Vitro Toxicity

Abstract

Predictive toxicity and structure–activity relationships (SARs) are raising interest since the number of nanomaterials has become unmanageable to assess their toxicity with a classical case-by-case approach. Graphene-based materials (GBMs) are among the most promising nanomaterials of this decade and their application might lead to several innovations. However, their toxicity impact needs to be thoroughly assessed. In this regard, we conducted a study on 22 GBMs to investigate their potential SARs by performing a complete physicochemical characterization and in vitro toxicity assessment (on RAW264.7 cells). We used GBMs of variable lateral size (0.5–38 µm), specific surface area (SSA, 30–880 m²/g), and surface oxidation (2–17%). We observed that reduced graphene oxides (RGOs) were more reactive than graphene nanoplatelets (GNPs), potentially highlighting the role of GBM’s surface chemistry and surface defects density in their biological impact. We also observed that for GNPs, a smaller lateral size caused higher cytotoxicity. Lastly, GBMs showing a SSA higher than 200 m²/g were found to induce a higher ROS production. Mechanistic explanations are proposed in the discussion. In conclusion, pairing a full physicochemical characterization with a standardized toxicity assessment of a large set of samples allowed us to clarify SARs and provide an additional step toward safe-by-design GBMs.

Exploring graphene-based materials’ genotoxicity: inputs of a screening method

“…In this regard, we can probably rule out a direct clastogenicity mechanism. Some GBMs appear to have a high genotoxic impact even at quite low doses, this is not completely surprising as some of these samples also show a very high impact for other in vitro studies performed on RAW 264.7 (Achawi et al 2021a) and on an acellular FRAS assay (Achawi et al 2021b).…”

“…Cells were then exposed to GBMs with exposure doses from 8 to 75 µg/cm² for 24 hours. ROS production was measured through OxiSelect™ Intracellular ROS Assay Kit (STA-342) as previously reported (Achawi et al 2021a).…”

Cytotoxicity of Carbon Nanotubes, Graphene, Fullerenes, and Dots

“…The toxicology of carbon nanomaterials was studied for carbon nanotubes [1][2][3][4][5][6][7][8][9][10][11][12][13][14], graphene [15][16][17][18][19][20][21][22][23][24][25][26][27][28], fullerenes [29][30][31][32][33], and dots [34][35][36][37][38]. Most of the work deals with microorganisms, animals, and humans.…”

Graphene Oxides (GOs) with Different Lateral Dimensions and Thicknesses Affect the Molecular Response in Chironomus riparius

“…The cytotoxicity induced by graphene materials was tested in various species, such as prokaryotes, bacteria, viruses, plants, invertebrates and mammals, including human and animal cells [ 5 , 6 , 7 , 8 , 9 , 10 ]. Several studies suggest that the size of the material will determine how it interacts with cells [ 11 , 12 , 13 ]. A previous work carried out with diverse cell lines has shown that GO with different side-chain dimensions has been able to cross the cell membrane [ 2 ].…”