A Metal-Free Mesoporous Carbon Dots/Silica Hybrid Type I Photosensitizer with Enzyme-Activity for Synergistic Treatment of Hypoxic Tumor

As a less O-2-dependent photodynamic therapy (PDT), type I PDT is an effective approach to overcome the hypoxia-induced low efficiency against solid tumors. However, the commonly used metal-involved agents suffer from the long-term biosafety concern. Herein, a metal-free type I photosensitizer, N-doped carbon dots/mesoporous silica nanoparticles (NCDs/MSN, approximate to 40 nm) nanohybrid with peroxidase (POD)-like activity for synergistic PDT and enzyme-activity treatment, is developed on gram scale via a facile one-pot strategy through mixing carbon source and silica precursor with the assistance of template. Benefiting from the narrow bandgap (1.92 eV) and good charge separation capacity of NCDs/MSN, upon 640 nm light irradiation, the excited electrons in the conduction band can effectively generate O-2(center dot-) by reduction of dissolved O-2 via a one-electron transfer process even under hypoxic conditions, inducing apoptosis of tumor cells. Moreover, the photoinduced O-2(center dot-) can partially transform into more toxic (OH)-O-center dot through a two-electron reduction. Moreover, the POD-like activity of NCDs/MSN can catalyze the endogenous H2O2 to (OH)-O-center dot in the tumor microenvironment, further synergistically ablating 4T1 tumor cells. Therefore, a mass production way to synthesize a novel metal-free type I photosensitizer with enzyme-mimic activity for synergistic treatment of hypoxic tumors is provided, which exhibits promising clinical translation prospects.