Surface-engineered graphene navigate divergent biological outcomes toward macrophages.

The "nano-bio" interface profoundly shapes the interaction between cells and nanomaterials and can even decide a cell's fate. As a nascent two-dimensional material, graphene has many unique attributes and is proposed to be a promising candidate for biomedical applications. Thus, for graphene-based applications, it is necessary to clarify how the graphene surface navigates biological outcomes when encountering "janitorial" cells (macrophages). For this purpose, we synthesized nanographene oxide (nGO) and engineered the surface with polyethylene glycol (PEG), bovine serum albumin (BSA), and poly(ether imide) (PEI). In contrast to pristine nGO, decoration with PEG and BSA hindered endocytosis and improved their benignancy toward macrophages. Contrarily, nGO-PEI commenced with favorable endocytosis but then suffered stagnation due to compromised macrophage viability. To unravel the underlying mechanisms regulating these diverse macrophage fates, we built a stepwise analysis. Compared to the others, nGO-PEI tended to interact electrostatically with mitochondria after their cellular internalization. Such an unexpected encounter disrupted the normal potential and integrity of mitochondria and then elicited an alteration in reactive oxygen species and cytochrome c. These responses further initiated the activation of the caspase family and ultimately dictated cells to undergo apoptosis. The advances described above will complement our knowledge of graphene functionality and serve to guide its application in biotechnological applications.