The direct catalytic synthesis of ultrasmall Cu2O-coordinated carbon nitrides on ceria for multimodal antitumor therapy

Engineering chem-/sono-/photo-multimodal antitumor therapies has become an efficient strategy to combat malignant tumors. However, the existence of hypoxia in the tumor microenvironment (TME) leads to limited sonodynamic or photodynamic efficiency because O₂ is the key reactant during the process of generation of reactive oxygen species (ROS). Here, to design a desirable platform that can simultaneously convert H₂O₂ in the TME into ROS and O₂ for efficient chem-/sono-/photo-multimodal tumor therapies, we have created ultrasmall Cu₂O-coordinated carbon nitride on a biocompatible ceria substrate (denoted as Cu₂O-CN_x@CeO₂) via a self-assisted catalytic growth strategy. The chemical and morphological structures, ROS and O₂ generation activities, and chemo-/photo-/sono-dynamic specificities of Cu₂O-CN_x@CeO₂ when serving as multifunctional biocatalytic agents were systematically disclosed. The experimental studies validated that Cu₂O-CN_x@CeO₂ presents state-of-the-art peroxidase-like and catalase-like activities. Moreover, the light excitation and ultrasound irradiation were also demonstrated to boost ROS production. The in vitro and in vivo experiments suggest that Cu₂O-CN_x@CeO₂ can efficiently inhibit the growth of malignant melanoma via chem-/sono-/photo-multimodal antitumor ability. We believe that applying these new biocatalysts with dual catalytic activities of producing ROS and O₂ will offer a new path for engineering multimodal nanoagents to combat malignant tumors.