Photocatalytically Active Graphitic Carbon Nitride as an Effective and Safe 2D Material for In Vitro and In Vivo Photodynamic Therapy

Thanks to its photocatalytic property, graphitic carbon nitride (g-C₃ N₄ ) is a promising candidate in various applications including nanomedicine. However, studies focusing on the suitability of g-C₃ N₄ for cancer therapy are very limited and possible underlying molecular mechanisms are unknown. Here, it is demonstrated that photoexcitation of g-C₃ N₄ can be used effectively in photodynamic therapy, without using any other carrier or additional photosensitizer. Upon light exposure, g-C₃ N₄ treatment kills cancer cells, without the need of any other nanosystem or chemotherapeutic drug. The material is efficiently taken up by tumor cells in vitro. The transcriptome and proteome of g-C₃ N₄ and light treated cells show activation in pathways related to both oxidative stress, cell death, and apoptosis which strongly suggests that only when combined with light exposure, g-C₃ N₄ is able to kill cancer cells. Systemic administration of the mesoporous form results in elimination from urinary bladder without any systemic toxicity. Administration of the material significantly decreases tumor volume when combined with local light treatment. This study paves the way for the future use of not only g-C₃ N₄ but also other 2D nanomaterials in cancer therapy.