A Molybdenum Disulfide Nanozyme with Charge‐Enhanced Activity for Ultrasound‐Mediated Cascade‐Catalytic Tumor Ferroptosis

Abstract The deficient catalytic activity of nanozymes and insufficient endogenous H 2 O 2 in the tumor microenvironment (TME) are major obstacles for nanozyme‐mediated catalytic tumor therapy. Since electron transfer is the basic essence of catalysis‐mediated redox reactions, we explored the contributing factors of enzymatic activity based on positive and negative charges, which are experimentally and theoretically demonstrated to enhance the peroxidase (POD)‐like activity of a MoS 2 nanozyme. Hence, an acidic tumor microenvironment‐responsive and ultrasound‐mediated cascade nanocatalyst (BTO/MoS 2 @CA) is presented that is made from few‐layer MoS 2 nanosheets grown on the surface of piezoelectric tetragonal barium titanate (T‐BTO) and modified with pH‐responsive cinnamaldehyde (CA). The integration of pH‐responsive CA‐mediated H 2 O 2 self‐supply, ultrasound‐mediated charge‐enhanced enzymatic activity, and glutathione (GSH) depletion enables out‐of‐balance redox homeostasis, leading to effective tumor ferroptosis with minimal side effects.