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

Abstract

AbstractAs a less O2‐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, ≈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 O2•− by reduction of dissolved O2 via a one‐electron transfer process even under hypoxic conditions, inducing apoptosis of tumor cells. Moreover, the photoinduced O2•− can partially transform into more toxic •OH through a two‐electron reduction. Moreover, the POD‐like activity of NCDs/MSN can catalyze the endogenous H2O2 to •OH 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.