Metal-phenolic functionalized covalent organic polymer nanozyme for tumor microenvironment-responsive,...

In this study, we synthesized a covalent organic polymer (COP) nanozyme functionalized with a metal-phenolic network (MPN) (COP@MPN). This complex exhibited enhanced physiological stability and multiple enzyme-mimicking activities, including oxidase (OXD), peroxidase (POD), catalase, glutathione oxidase, and superoxide dismutase activities. The catalytic free energies for the POD- and OXD-mimicking reactions of the COP@MPN nanozyme were calculated using density functional theory. The results demonstrate that surface functionalization with MPN improves the catalytic activity of the nanozyme. Importantly, the POD- and OXD-mimicking activities of COP@MPN were markedly enhanced under stimulation by the tumor microenvironment (TME) and the photothermal effect of COPs. In vitro and in vivo cytotoxicity tests showed that COP@MPN increased intracellular reactive oxygen species (ROS) levels in TME, achieving highly efficient oral squamous cell carcinoma therapy via photothermal-enhanced ROS generation. These findings underscore the potential of the COP@MPN nanozyme as an efficient therapeutic agent for oral squamous cell carcinoma by combining TME-activated catalytic and photothermal treatments, offering a multifunctional platform for synergistic cancer therapy.