Implant-related infections manifest as stubborn biofilm formation, antibiotic resistance, and immune evasion. Due to the limited efficacy of traditional treatments, they pose a serious clinical burden in the field of orthopedics. To address this challenge, innovative strategies are needed that can both disrupt the biofilm and overcome the bacterial defense mechanisms. Therefore, we have developed patterned copper phosphate (CuP) nanoenzymes with dual enzyme activity (peroxidase and glutathione peroxidase-like) through similar copper phosphorylation-induced death and a two-component system (TCS) inhibition, to synergistically eliminate the biofilm of implant-related infections. In vitro antibacterial experiments demonstrated that CuP nanoenzymes significantly inhibited and disrupted bacterial biofilms. These CuP nanoenzymes consumed glutathione (GSH) while generating reactive oxygen species (ROS), disrupting the bacterial membrane, interfering with the TCA cycle and glycolysis and other metabolic processes. Transcriptional analysis revealed that the expression of oxidative phosphorylation genes and quorum sensing regulatory factors was inhibited, confirming the dual targeting of bacterial viability and dissemination. In vivo, CuP nanoenzymes effectively eliminated biofilm infections on implants, reduced inflammatory responses, and exhibited excellent biocompatibility. Through the integration of enzymatic ROS amplification, metabolic interference, and TCS inhibition, this strategy provides a transformative approach to anti-implant infection, surpassing traditional therapies in terms of efficacy and safety. This study was published in Bioactive Materials under the title "Copper phosphate nanozymes combat implant-related infections by inducing cuproptosis-like death and inhibiting the two-component system".

DOI: 10.1016/j.bioactmat.2026.02.042