Regulation of the Endocytosis System Using Ultrathin g-C₃N₄ Nanosheets for Enhanced Photodynamic Therapy of Glioma

Glioma is the most aggressive form of brain cancer. Photodynamic therapy (PDT) has emerged as a promising treatment method for glioma; however, its efficacy is often hindered by the blood-brain barrier (BBB) and the need for precise tumor cell targeting. In the present study, a facile strategy is found to enhance the penetration of the BBB and the internalization efficiency by exfoliating the (100) crystal plane of g-C₃N₄ (CN) using liquid nitrogen, resulting in ultrathin graphitic carbon nitride (CN12) nanosheets with hydroxyl-rich surfaces. These CN12 nanosheets significantly enhanced the permeability of the BBB, increased the endocytosis efficiency by four times, and elevated reactive oxygen species (ROS) in vivo by 2.5 times. The as-formed CN12 nanosheets successfully targeted the mitochondrial function of tumor cells, promoted ROS generation, and induced apoptosis. Moreover, the combination of CN12 nanosheets with photoelectrode implantation completely eradicated tumors within 10 d without recurrence or severe side effects.