Fluorine-containing graphene quantum dots with a high singlet oxygen generation applied for photodynamic therapy

Recently, graphene quantum dots (GQDs) have been extensively studied in biomedical areas such as bio-imaging, bio-sensing and photothermal therapy due to their superior optical and physiochemical properties compared to traditional organic biomarkers. Application of GQDs in photodynamic therapy (PDT) has been explored since 2014, but currently the main challenges are inadequate singlet oxygen (1O2) quantum yield (QY), poor solubility and biocompatibility. Herein, we report on the synthesis of a new class of fluorine-containing GQDs (F-GQDs) by an oxidative cutting method using fluorinated graphite as the raw material. The as-synthesized F-GQD sample demonstrates an average particle size of 2.1 nm with a fluorine doping content of 1.43%. The F-GQDs have a better water solubility and biocompatibility than the GQDs, and emit strong green fluorescence at 365 nm excitation with a relative fluorescence QY of 13.72%. Moreover, the fluorescence imaging effect as well as photodynamic activity was successfully tested in both an in vitro HepG2 cell line model and a 3D multicellular spheroid model, the latter of which mimics the tumour microenvironment. Further studies using UV-visible spectroscopy to monitor the degradation of water-soluble 9,10-anthracenediyl-bis(methylene)dimalonic acid (ABDA) demonstrate that the F-GQD sample generates 1O2 efficiently (QY = 0.49) under visible light irradiation. Compared to non-fluorinated GQDs, the as-reported F-GQDs appear to be a more promising photosensitizer for image-guided PDT.