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However, the release of Cu ions that are not specific to bacteria can trigger cuproptosis and lead to irreversible damage to healthy tissues. Herein, carbon dots (CDs) with triplet\u2010mediated sonodynamic activity are deposited on cuproptosis inducer (Cu\n                    <jats:sub>2<\/jats:sub>\n                    O) to achieve the multiple amplification effects of antibacterial and antibiofilm activities. First, the sonodynamic and chemodynamic activities of single\u2010component sonosensitizers\/nanozymes are significantly augmented by the formation of heterojunction sonozymes. Second, Cu\n                    <jats:sub>2<\/jats:sub>\n                    O\/CD with bacterial microenvironment (BME)\u2010responsive degradation features realizes the bacterium\u2010specific release of Cu\n                    <jats:sup>+<\/jats:sup>\n                    , CDs, and Cu\n                    <jats:sup>2+<\/jats:sup>\n                    , which can not only achieve cascade amplification of reactive oxygen species (ROS) production through depleting GSH but also realize the bacterium\u2010specific cuproptosis\u2010like death. Notably, transcriptome sequencing analysis indicates that Cu\n                    <jats:sub>2<\/jats:sub>\n                    O\/CD\u2010mediated combination therapy damaged bacterial ribosomes and ion transport, facilitating the influx of Cu ions and disrupting the bacterial TCA cycle. Collectively, the synergistic antibacterial treatments of SDT, CDT, and cuproptosis\u2010like death via Cu\n                    <jats:sub>2<\/jats:sub>\n                    O\/CD can realize the thorough sterilization and biofilm elimination. The work presents a novel perspective on how to optimize the function and safety of cuproptosis inducers, ultimately maximizing therapeutic advantages while minimizing harm to normal tissues.\n                  <\/jats:p>","DOI":"10.1002\/smll.202505266","type":"journal-article","created":{"date-parts":[[2025,8,5]],"date-time":"2025-08-05T08:15:20Z","timestamp":1754381720000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Ultrasound\u2010Activated Heterojunction Sonozymes Trigger Bacterium\u2010Specific Cuproptosis\u2010Like Death for Enhanced Sonodynamic\u2010Chemodynamic Therapy of Multidrug\u2010Resistant Bacterial Infections"],"prefix":"10.1002","volume":"21","author":[{"given":"Pengfei","family":"Cheng","sequence":"first","affiliation":[{"name":"Department of Orthopedic Surgery Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine  Shanghai 200233 P. R. 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