Ligand-Modulated Catalytic Selectivity of Ag Clusterzyme for Relieving Multiorgan Injury via Inhabiting Acute Oxidative Stress.

The artificial enzymes at the atomic level have shown great potential in chemical biology and nanomedicine, and modulation of catalytic selectivity is also critical to the application of nanozymes. In this work, atomic precision Ag25 clusterzymes protected by single- and dual-ligand were developed. Further, the catalytic activity and selectivity of Ag25 clusterzymes were modulated by adjusting doping elements and ligand. The Ag24Pt1 shows more prominent antioxidant activity characteristics in the dual-ligand system, while the Ag24Cu1 possesses the superoxide dismutase-like (SOD-like) activity regardless of the single- or dual-ligand system, indicating modulated catalytic selectivity. In vitro experiments showed the Ag24Pt1-D can recover radiation induced DNA damages and eliminate the excessive reactive oxygen species (ROS) generated from radiation. Subsequent in vivo radiation protection experiments reveal that Ag24Cu1-S and Ag24Pt1-D can improve the survival rate of irradiated mice from 0 to 40% and 30%, respectively. The detailed biological experiments confirm that the Ag24Cu1-S and Ag24Pt1-D can recover the SOD and 3,4-methylenedioxyamphetamine (MDA) levels via suppressing the chronic inflammation reaction. Nearly 60% of Ag24Cu1-S and Ag24Pt1-D can be excreted after a 1 day injection, and no obvious toxicological reactions were observed 30 days after injection.