Better biocompatibility of nitrogen-doped graphene compared with graphene oxide by reducing cell autophagic flux blockage and cell apoptosis

Nitrogen-doped graphene (C2N), a novel graphene-based materials, has been proposed as a potential alternative to graphene oxide (GO) in biomedical applications. However, due to the challenges in synthesizing C2N, reports in the biomedical field are currently rare. Here, we have modified the reported procedure and successfully synthesized C2N nanoparticles at 120 degrees C, which we refer to as C2N-120. The toxicity and biocompatibility of GO and C2N-120 were evaluated using a mouse model injected with GO/C2N-120 via the tail vein, as well as cell models treated with GO/C2N-120. In vivo studies revealed that GO/C2N-120 showed similar distribution patterns after tail vein injection. The liver, spleen, and lung are the major nanoparticle uptake organs of GO and C2N-120. However, GO deposition in the major nanoparticle uptake organs was more significant than that of C2N-120. In addition, GO deposition caused structural abnormalities, increased apoptotic cells, and enhanced macrophage infiltration whereas C2N-120 exhibited fewer adverse effects. In vitro experiments were conducted using different cell lines treated with GO/C2N-120. Unlike GO which induced mitochondrial damage, oxidative stress, inflammatory response, autophagic flux blockage and cell apoptosis, C2N-120 showed lower cytotoxicity in cell models. Our data demonstrated that C2N-120 exhibits higher biocompatibility than GO, both in vivo and in vitro, suggesting its potential for biomedical application in the future.