Advances in ultrasound-mediated nanozyme systems in therapeutic applications.

Ultrasound-mediated nanozyme systems are emerging therapeutic platforms that couple externally controllable acoustic fields with enzyme-mimetic catalysis. Ultrasound can improve tissue delivery, penetration and local activation through cavitation, sonoporation, phase transition and piezoelectric effects, whereas nanozymes remodel pathological microenvironments by generating or scavenging reactive oxygen species (ROS), modulating oxygen availability, perturbing metabolism and restoring redox homeostasis. A central challenge is to distinguish true nanozyme catalysis from related ultrasound-responsive processes, including sonodynamic activation, piezocatalysis and ultrasound-triggered delivery. This review summarizes recent progress across tumors, drug-resistant bacterial and biofilm-associated infections, atherosclerosis, neurodegenerative diseases, osteochondral disorders, ischemia-reperfusion (I/R) injury, and tendon repair and tendinopathy. We highlight how ultrasound and nanozymes cooperate to overcome biological barriers, regulate oxidative stress and inflammation, remodel disease microenvironments and support tissue repair or functional recovery. We further discuss mechanistic heterogeneity, incomplete attribution of therapeutic effects, insufficient standardization of ultrasound parameters, material complexity, biodistribution and clearance, biosafety, and manufacturing challenges. The review argues that progress should be judged by catalytic attribution, disease-matched acoustic design and material exit routes, rather than by adding functions to already complex platforms. Overall, ultrasound-mediated nanozyme therapy should be viewed as a mechanism-dependent and disease-context-specific strategy whose translation will require clearer catalytic validation, acoustic reporting and safety evaluation.