A single-molecule graphene quantum dot: a novel efficient photosensitizer for photodynamic cancer therapy.

Graphene quantum dots (GQDs) can efficiently generate reactive oxygen species (ROS) under light irradiation, demonstrating significant potential for photodynamic therapy (PDT) applications. However, GQDs are often multicomponent mixtures with highly complex structures, which significantly hinders their clinical applications. Therefore, it is urgent to design and synthesize well-defined GQDs with excellent PDT performance. In this work, a novel single-molecule hydrophilic pure graphene quantum dot (HPGQD), containing 132 sp2 conjugated carbon atoms, was prepared through an organic synthetic route using single-benzene-ring molecules as precursors. The HPGQD features a unique D-12A structure, comprising one large electron donor center and 12 electron acceptors, which grants it exceptional ROS release capabilities with a singlet oxygen (1O2) quantum yield of 0.85. Notably, under light irradiation, the HPGQD can rapidly generate abundant ROS within 30 s and scavenge them after 10 min, which holds promise for eliminating the need for prolonged light avoidance in patients undergoing PDT. It has been successfully applied to both in vitro (IC50: 0.22 μmol L-1) and in vivo (tumor weight inhibition rate: 71%) PDT for cancer treatment. The innovative design, synthesis, and PDT application of the single-molecule HPGQD pave the way towards accelerated clinical applications of carbon nanomaterials, advancing the frontier of nanotherapeutic research.