Endogenous H2O2-Sensitive and Weak Acidic pH-Triggered Nitrogen-Doped Graphene Nanoparticles (N-GNMs) in the Tumor Microenvironment Serve as Peroxidase-Mimicking Nanozymes for Tumor-Specific Treatment

Nanozymes are emerging as a promising strategy for the treatment of tumors. Herein, to cope with the tumor microenvironment (TME), weak acidity (pH 5.6 to 6.8) and trace amounts of overexpressed hydrogen peroxide (H₂O₂) (100 µM–1 mM), we report nitrogen-doped graphene nanomaterials (N-GNMs), which act as highly efficient catalytic peroxidase (POD)-mimicking nanozymes in the TME for tumor-specific treatment. N-GNMs exhibit POD catalytic properties triggered by a weakly acidic TME and convert H₂O₂ into highly toxic hydroxyl radicals (•OH) thus causing the death of tumor cells while in the neutral pH surroundings of normal tissues, such catalysis is restrained and leaves normal cells undamaged thereby achieving a tumor-specific treatment. N-GNMs also display a high catalytic activity and can respond to the trace endogenous H₂O₂ in the TME resulting in a high efficiency of tumor therapy. Our in vitro chemical and cell experiments illustrated the POD-like activity of N-GNMs and in vivo tumor model experiments confirmed the significant inhibitory effect of N-GNMs on tumor growth.