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Conventional approaches, including oxygen delivery systems, small\u2010molecule redox drugs, and natural enzymes, can relieve hypoxia but suffer from poor tissue specificity, short duration of action, and limited stability. Nanozymes are engineered nanomaterials with enzyme\u2010like catalytic activity. Through controllable redox reactions, they can regulate oxygen generation or consumption, rebalance reactive oxygen species, and reprogram hypoxic microenvironments\u00a0at the cellular and tissue levels. In recent years, the field has shifted from empirical trial\u2010and\u2010error to rational nanozyme design, with a focus on defined active sites, disease\u2010responsive activity, and targeted delivery. Herein, we summarize the key design principles governing nanozyme catalytic performance and discuss the catalytic mechanisms involved in hypoxia regulation. We then examine how distinct pathological features of acute and chronic hypoxic microenvironments create different catalytic requirements and how nanozyme functions can be tailored accordingly. Furthermore, we provide an overview of nanozyme applications across hypoxia\u2010associated diseases and discuss emerging opportunities and barriers for clinical translation. This review is expected to provide insights for developing precise and clinically valuable hypoxia\u2010regulating nanozymes.<\/jats:p>","DOI":"10.1002\/adma.75154","type":"journal-article","created":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T08:33:56Z","timestamp":1791189236000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Hypoxia\u2010Regulating Nanozymes for Biomedicine"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-6975-2632","authenticated-orcid":false,"given":"Yuhan","family":"Yang","sequence":"first","affiliation":[{"name":"State Key Laboratory of Organic\u2013Inorganic Composites Beijing Key Laboratory of Green Chemicals Biomanufacturing College of Life Science and Technology Beijing University of Chemical Technology  Beijing 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