Tuning the Needling Length of Copper Single-Atom Nanozyme for Enhanced Cellular Uptake and Chemodynamic Therapy
Xinyi Shi, Tianwei Song, Yinglong Wu, Xiangyang Li, Xiangfu Meng, Yong Qian, Chenyang Bi, Dongdong Wang, Junchao Qian, Yanli Zhao, Hui Wang
Abstract
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.