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Herein, we report a sequential multimodal platform embedding a self-adaptive IrPtCu nanozyme into a madecassoside-enriched hyaluronic acid hydrogel (HIPCM) for rapid bacterial eradication and accelerated wound healing. Leveraging trimetallic synergy and pH-adaptive reactive oxygen species (ROS) regulation, IrPtCu nanozyme exhibits strong oxidase, peroxidase, glutathione oxidase, and glutathione peroxidase-like activities, enabling efficient ROS generation and potent antibacterial performance. After disinfection, it switches to ROS scavenging through superoxide dismutase and catalase-like cascades, alleviating oxidative stress and cooperating with madecassoside to promote tissue repair. In a methicillin-resistant\n                    <jats:italic>Staphylococcus aureus<\/jats:italic>\n                    (\n                    <jats:italic>MRSA<\/jats:italic>\n                    )-infected mouse model, HIPCM demonstrates strong antibacterial efficacy, promotes M2 macrophage polarization and angiogenesis, and accelerates high-quality repair. Preclinical studies in Bama mini-pigs further confirm improved collagen deposition, hair follicle regeneration, and functional restoration. This work offers a comprehensive strategy integrating adaptive nanozymes and natural herbal medicines for treating drug-resistant wounds.\n                  <\/jats:p>","DOI":"10.1038\/s41467-026-73672-2","type":"journal-article","created":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T11:56:25Z","timestamp":1779969385000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Self-adaptive nanozymes with enhanced multi-enzyme activities for sequential multimodal therapy of drug-resistant bacteria-infected wounds"],"prefix":"10.1038","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1731-1887","authenticated-orcid":false,"given":"Xiaoyong","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hang","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-4567-9866","authenticated-orcid":false,"given":"Yao","family":"Xiao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuxuan","family":"Gong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dandan","family":"Che","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wanyi","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guoxing","family":"You","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7290-352X","authenticated-orcid":false,"given":"Xiyun","family":"Yan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-3298-2251","authenticated-orcid":false,"given":"Quan","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6285-1933","authenticated-orcid":false,"given":"Kelong","family":"Fan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4586-4526","authenticated-orcid":false,"given":"Gan","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,5,28]]},"reference":[{"key":"73672_CR1","doi-asserted-by":"publisher","first-page":"50","DOI":"10.1038\/s41572-022-00377-3","volume":"8","author":"V Falanga","year":"2022","unstructured":"Falanga, V. et al. 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