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Accurate distinguish of cancer cells through fluorescence plays an important role in cancer diagnosis. Here we synthesized a blue fluorescent nitrogen-doped graphene quantum dots (N-GQDs) from citric acid and diethylamine via one-step hydrothermal synthesis method which was simple and quick to avoid by-products, and highlighted the binding sites to achieve precise combination. Due to the nitrogen element doping, amide II bond was amply obtained and abundant binding sites were provided for hyaluronic acid (HA) conjugation. N-GQDs solution with different pH value was then conjugated to HA via an amide bond for the recognition of human breast cancer cells (MCF-7 cells), and the formation of amide bond was more favorable under alkaline conditions. HA conjugated N-GQDs (HA-N-GQDs) were combined with CD44 which was over expressed on the surface of MCF-7 cells, resulting in MCF-7 cells performing stronger fluorescence. HA-N-GQDs showed high fluorescence, low toxicity, and good cytocompatibility, which held it play a role in fluorescence imaging for accurate identification of cancer cells.

This paper reports the preparation and application of folic acid-conjugated nitrogen-doped graphene quantum dots (N-GQDs) as a fluorescent diagnostic material for MCF-7 cells of breast cancer. N-GQDs were prepared by a hydrothermal method using citric acid as the carbon source and diethylamine as the nitrogen source. The doping of different amounts of nitrogen content was effectively controlled by diethylamine. As the amount of nitrogen increased, more binding sites on the N-GQDs were supplied to the folic acid. Laser confocal scanning microscopy showed that increased folic acid binding facilitated the recognition of and entry to cancer cells, which made the labeled cells emit a stronger fluorescence and thus the cancer cells could be better detected. Cytotoxicity tests showed that the material was of low cytotoxicity, making it a promising prospect for fluorescent probes.