Tuning the Needling Length of Copper Single-Atom Nanozyme for Enhanced Cellular Uptake and Chemodynamic Therapy

Single-atom nanozymes (SAEs) with a high catalytic performance have received worldwide attention in tumor therapy. The current SAEs still suffer from a low cell penetration efficiency and tumor accumulation, limiting their therapeutic effect during treatment. Herein, a typical urchin-like carbon-supported copper single-atom nanozyme (UCCSE) is designed for enhanced cascade chemodynamic therapy. The UCCSE is synthesized through a one-step carbonization-reduction strategy using dopamine and copper chloride as precursors. The structure endows UCCSE with enhanced membrane penetration via endocytosis and tumor cell uptake abilities. Upon internalization, the as-prepared UCCSE possesses peroxidase (POD)-mimicking activity for continuous hydroxyl radical (•OH) generation as well as glutathione peroxidase (GPx)-mimicking activity for glutathione depletion. Both cellular and animal experiments exhibit noteworthy needling-length-dependent tumor suppression effects with negligible systemic toxicity. This work provides a simple paradigm for enhanced tumor catalytic therapy through rational regulation of morphology.