Abstract

The ear, a highly sophisticated sensory organ responsible for detecting environmental sound waves, remains continuously at risk due to the high prevalence of otitis media (OM). This condition, primarily caused by pathogen invasion and the subsequent inflammatory cytokine storm, represents one of the most significant global health burdens, with estimated annual costs ranging from US $3 to $5 billion expenses. In response to this challenge, we have developed a sulfur-doped copper–zinc single-atom nanozyme (CuZn-NS SAzymes) that combines potent bactericidal capabilities with precise immunomodulatory functions. This nanozymes exhibit dual enzymatic activity: sulfur doping enhances peroxidase-like activity for enhanced bacterial killing, while subsequent catalase-like activity scavenges residual H₂O₂, establishing an “attack- and- self-protection” cycle. The nanozyme’s ultrasmall hydrodynamic diameter enhances cellular uptake, resulting in a marked reduction in pro-inflammatory cytokines and a simultaneous increase in anti-inflammatory mediators, effectively disrupting the oxidative-stress-inflammation axis. CuZn-NS SAzymes thus represent a promising therapeutic strategy for deep sensory organ infections.