Structure–Biomedical Activity Relationship of Tunable Ceria–Graphene Nanocomposites Leading to Divergent Cellular Responses

Graphene-based nanomaterials (GBNs) have emerged as promising candidates for diverse biomedical applications, but their clinical translation has been hindered by inherent cytotoxicity. We synthesized three distinct cerium-containing graphene nanocomposites using a single-step, in situ electrochemical exfoliation process and investigated their structure–activity relationships in normal dermal fibroblasts (BJ) and hepatocarcinoma cells (HepG2). The properties of the resulting nanocomposites, including their morphology, cerium loading, and the surface redox state (Ce3+/Ce4+ ratio) were directly dictated by the employed synthesis parameters, such as the cerium salt precursor and its concentration. These distinct materials induced differential cellular responses that ranged from preferential cytotoxicity in HepG2 cells to a significant cytostimulatory effect and increased ATP levels in BJ fibroblasts, particularly in EXF3-treated cells. Our findings indicate that by employing the in situ electrochemical exfoliation method, the hybrid graphene compounds might be further tailored for specific purposes, moving the narrative beyond the mere functionalization of the graphene in order to achieve biocompatibility.