Graphene Triggers Inflammation in Murine Microglia via Phagocytosis

Graphene and related materials are increasingly used in biomedical technologies, including neural interfaces, but their impact on brain immune cells remains poorly understood. The present study investigates the acute response of murine microglial SIM-A9 cells to single-layer graphene, with carbon nanotubes and graphene nanoplatelets included as comparative controls. Short-term culture for 3 h on graphene-coated substrates did not induce cytotoxicity but promoted inflammatory activation, reflected in increased release of the cytokine tumor necrosis factor alpha (TNF-α). Raman spectroscopy revealed partial removal of the graphene layer, indicating phagocytic uptake by microglia. Supporting this mechanism, small carbon nanotubes elicited a similar inflammatory response, whereas larger graphene nanoplatelets, which are less readily internalized, did not. Potential contamination by bacterial endotoxin could be excluded using the lipopolysaccharide (LPS) inhibitor polymyxin B. Comparative proteomic analysis demonstrated that ingestible graphene alters pathways related to inflammation, cytoskeleton organization, and cell proliferation. These findings indicate that graphene can affect microglia through phagocytosis and highlight the importance of preventing delamination from biomedical devices to ensure safe use.