Engineering charge density in s-block potassium single-atom nanozyme for amplified ferroptosis in glioblastoma therapy
Hongjia Zheng, Guo Zhang, Fuxiang Chen, Qi Zhong, Yi Hu, Chengzhong Du, Huimin Wang, Penghui Wei, Wei Huang, Dengliang Wang, Yang Zhu, Dezhi Kang
Abstract
Single-atom nanozyme (SAN) are emerging as a cutting-edge platform for next-generation nanozyme on account of their remarkable catalytic efficiency and well-defined electronic/geometric structures. While most SAN focus on transition metal atoms as active sites, s-block main group metals have traditionally been considered catalytically inert. Herein, we develop an s-block potassium single-atom nanozyme (K-SAN) featuring K-N 4 active sites. The s orbital in single-atom K plays a distinct and critical role in the adsorption of intermediates, enabling single-atom K to exhibit an intermediate adsorption mode different from that of transition metals. K-SAN effectively induces ferroptosis in tumor cells by initiating a reactive oxygen species storm and depleting reductive glutathione, which leads to the accumulation of lipid peroxides and the inactivation of glutathione peroxidase 4 (GPX4). Furthermore, under 808 nm laser irradiation, the catalytic activities of K-SAN are strengthened, leading to a significant inhibition of tumor growth in vivo. Density functional theory calculations and experimental results together demonstrate the defined catalytic mechanism and impressive therapeutic effect of K-SAN, highlighting its unoccupied orbitals, which can accept electron donation-a key advantage over transition metal-based SAN. This study provides significant insights for the rational design and exploration of catalytic mechanisms in s-block SAN with potent antitumor efficacy.