Multiple therapeutic mechanisms of pyrrolic N-rich g-C3N4 nanosheets with enzyme-like function in the tumor microenvironment

作者：Song, Shanshan; Yang, Miao; He, Fei^*; Zhang, Xiao^*; Gao, Yijun; An, Baichao; Ding, He; Gai, Shili; Yang, Piaoping^*

来源：Journal of Colloid and Interface Science, 2023, 650: 1125-1137.

DOI：10.1016/j.jcis.2023.06.177

• Catalase-like nanozymes
• Tumor microenvironment-adjusted
• Photodynamic therapy
• Tumor catalytic therapy

Nanozyme-based synergistic catalytic therapies for tumors have attracted extensive research attention. However, the unsatisfactory efficiency and negative impact of the tumor microenvironment (TME) hinder its clinical applications. In this study, we provide an easy method to prepare transition metals loaded onto pyrrolic nitrogenrich g-C3N4 (PN-g-C3N4) for forming metal-N4 sites. This N-rich material effectively transfers electrons from g-C3N4 to metal-N4 sites, promotes the oxidation-reduction reaction of metals with different valence states, and improves material reusability. Under TME conditions, copper ions loaded onto PN-g-C3N4 (Cu-PN-g-C3N4, CPC) can produce center dot OH through a Fenton-like reaction for tumor inhibition. This Fenton-like reaction and tumor cell inhibition can be improved further by a photodynamic effect caused by light irradiation. We introduced upconversion nanoparticles (UCNPs) into CPC to obtain nano-enzymes (UCNPs@Cu-PN-g-C3N4, UCPC) for effectively penetrating the tissue, which emits light corresponding to the UV absorption region of CPC when excited with 980 nm near-infrared (NIR) light. The nanoplatform can reduce H2O2 concentration upon exposure to NIR light; this induces an increase in dissolved oxygen content and produces a higher supply of reactive oxygen species (ROS) for destroying tumor cells. Owing to the narrow bandgap (1.92 eV) of UCPC under 980 light irradiation, even under the condition of hypoxia, the excited electrons in the conduction band can reduce insoluble O-2 through a single electron transfer process, thus effectively generating O-2(center dot-). Nanoenzyme materials with catalase properties produce three types of ROS (center dot OH, O-2(center dot-) and O-1(2)) when realizing chemodynamic and photodynamic therapies. An excellent therapeutic effect was established by killing cells in vitro and the tumor-inhibiting effect in vivo, proving that the prepared nanoenzymes have an effective therapeutic effect and that the endogenous synergistic treatment of multiple treatment technologies can be realized.

• 单位
  南方医科大学; 哈尔滨工程大学