Graphene Quantum Dots with Pyrrole N and Pyridine N: Superior Reactive Oxygen Species Generation Efficiency for Metal-Free Sonodynamic Tumor Therapy

Those responsible for the development of sonosensitizers are faced with a dilemma between high sonosensitization efficacy and good biosecurity that limited the development of sonodynamic therapy (SDT). Herein, inspired by the intriguing therapeutic features of SDT and the potential catalytic activity of graphene quantum dots, the potential of N-doped graphene quantum dots (N-GQDs) to act as a sonosensitizer is demonstrated. The superior sonosensitization effect of N-GQDs is believed to be three to five times higher than that of traditional sonosensitizers (such as porphyrin, porphyrin Mn, porphyrin Zn, TiO2, etc.). More importantly, the sonochemical mechanism of N-GQDs is revealed. Pyrrole N and pyridine N are believed to form catalytic centers in sonochemical processing of N-GQDs. This knowledge is important from the perspective of understanding the structure-dependent SDT enhancement of carbon nanostructure. Moreover, N-GQDs modified by folic acid (FA-N-GQDs) show a high marker rate for tumor cells (greater than 96%). Both in vitro and in vivo therapeutic results have exhibited high tumor inhibition efficiency (greater than 90%) of FA-N-GQDs as sonosensitizers while the oxidative stress response of tumor cells is activated through the PEX pathway and induced apoptosis via the p53 pathway.