Biocompatible copper single-atom site nanozyme for parallel tumor therapy

Reasonable design and construction of artificial enzymes with excellent catalytic activity, good stability and superior biocompatibility is essential for tumor therapy. Single-atom site catalysts (SAs) with well-defined atomic structure and electronic coordination environments have been regarded as a new type of nanozyme that can exhibit excellent catalytic activity like natural enzymes. Here, we constructed a copper-based single-atom site nanozyme (named Cu-N,O/C) that stabilized in hollow carbon nanosphere, and the electronic structure of the single copper active center was precisely controlled by regulating the coordination of nitrogen and oxygen. The well-designed Cu-N₃O active center enables the Cu-N,O/C nanozyme to exhibit multiple extraordinary enzyme-mimicking activities by synchronously catalyzing the generation of reactive oxygen species (ROS), which can effectively inhibit the growth of tumor cell <i>in vitro</i> and <i>in vivo</i>, and the therapeutic effect pronounced enhanced in the weak acidic tumor environment. In addition, the remarkable near infrared spectroscopy (NIR)-photothermal conversion activity of Cu-N,O/C nanozyme significantly enhances the efficiency of cancer cell killing. Therefore, single-atom site nanozyme possesses significant therapeutic efficacy for tumor therapy through multiple ROS and photothermal activity.