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Here, we present a pH\u2010adaptive nanozyme platform (MICP@HG) that orchestrates stage\u2010specific antibacterial and immunomodulatory activities throughout sepsis progression. The platform integrates near\u2010infrared imaging, catalytic therapy, and immune regulation into a single construct. In acidic infectious microenvironments, the Cu\u2013piceatannol shell exhibits peroxidase\u2010mimicking activity and induces cuproptosis\u2010like bacterial death through metabolic collapse and redox imbalance. As the microenvironment normalizes, the nanozyme shifts toward antioxidative and anti\u2010inflammatory functions via superoxide dismutase (SOD)\u2010 and catalase (CAT)\u2010like activities. Concurrently, the hyaluronic acid (HA)\/\u03b2\u2010glucan coating facilitates infection\u2010targeted delivery and reprograms macrophages toward a reparative phenotype while restoring immune responsiveness. This dynamic functional transition enables efficient eradication of multidrug\u2010resistant bacteria, attenuation of systemic inflammation, and preservation of organ function, ultimately achieving complete survival in polymicrobial sepsis models. Notably, the platform also elicits a vaccine\u2010like trained immunity effect that confers protection against reinfection. This work establishes a paradigm for temporally programmed nanotherapy that aligns therapeutic function with disease progression, offering a precision strategy for the treatment of complex inflammatory disorders.<\/jats:p>","DOI":"10.1002\/advs.77231","type":"journal-article","created":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T05:17:20Z","timestamp":1788931040000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Disease\u2010Stage Synchronized Nanozyme Therapy for Polymicrobial Sepsis through Adaptive Catalytic and Immune Reprogramming"],"prefix":"10.1002","author":[{"given":"Anlai","family":"Zou","sequence":"first","affiliation":[{"name":"Department of Clinical Laboratory Sir Run Run Shaw Hospital of Zhejiang University School of Medicine  Hangzhou Zhejiang China"},{"name":"Key Laboratory of Precision Medicine in Diagnosis and Monitoring Research of Zhejiang Province  Hangzhou Zhejiang 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