Engineering charge density in s-block potassium single-atom nanozyme for amplified ferroptosis in glioblastoma therapy.

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-N4 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.