A novel “OFF-ON” biosensor based on nanosurface energy transfer between gold nanocrosses and graphene quantum dots for intracellular ATP sensing and tracking

•A NSET assembly was constructed by using gold nanocrosses (AuNCs) and graphene quantum dots (GQDs).•Folic acid modified AuNCs-GQDs could distinguish and enhance endocytosis of folic acid receptor positive (FR+) cancer cells.•The sensor was highly specific and the response range was close to the actual intracellular ATP level.•The sensor showed low cytotoxicity and excellent performance in intracellular ATP sensing and tracking. An efficient strategy based on the nanosurface energy transfer (NSET) between gold nanocrosses (AuNCs) and graphene quantum dots (GQDs) for intracellular ATP sensing and tracking was first developed. GQDs and AuNCs assembled in the bases of complementary matching principle, which result in the fluorescence quenching via NSET. In the presence of ATP, aptamer recognized and combined with ATP, caused the distance change between GQDs and AuNCs. The fluorescence intensity was proportional to ATP concentration, which was represented by the equation y = 176.67 x + 335.51 (R2 = 0.9916) with the detection limit of 0.27 mM (3δ, n = 11). Moreover, the proposed “OFF-ON” sensor showed low cytotoxicity and excellent performance in intracellular ATP sensing, which will provide new possibilities for labeling of small biological molecules.