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In this study, a biodegradable layered double hydroxide\u2013like high\u2010entropy material (LDH\u2010HEM) composed of Fe, Cu, Zn, Mn, and Al is reported as an ultrasound\u2010activated sonosensitizer for eradicating\n                    <jats:italic>Pseudomonas aeruginosa<\/jats:italic>\n                    (\n                    <jats:italic>P. aeruginosa<\/jats:italic>\n                    ) infections. Experimental evidence and theoretical analysis collectively reveal that the multi\u2010metal synergy effectively narrows the bandgap and enhances exciton generation under ultrasound excitation, while ultrasonic pressure\u2010induced lattice distortion enables a strain\u2010driven autonomous type\u2010II heterojunction that promotes charge separation. Under mild ultrasound (1.0\u00a0MHz, 0.5\u00a0W cm\n                    <jats:sup>\u22122<\/jats:sup>\n                    , 10\u00a0min) stimulation, LDH\u2010HEM generates abundant reactive oxygen species, achieving &gt;99% eradication of\n                    <jats:italic>P. aeruginosa<\/jats:italic>\n                    at a low dosage (50\u00a0\u00b5g mL\n                    <jats:sup>\u22121<\/jats:sup>\n                    ). In addition, LDH\u2010HEM reprograms macrophage polarization toward an M1 phenotype, thereby boosting bacterial phagocytosis and clearance. In murine models of subcutaneous abscesses and bacterial keratitis infected with\n                    <jats:italic>P. aeruginosa<\/jats:italic>\n                    , LDH\u2010HEM\u2010mediated sonodynamic therapy effectively eradicates pathogens and accelerates wound and corneal healing within 2 weeks. This work introduces a mechanochemically responsive and biodegradable high\u2010entropy platform for deep\u2010seated infection therapy and provides design principles for engineering multifunctional HEMs for biomedical translation.\n                  <\/jats:p>","DOI":"10.1002\/adma.75216","type":"journal-article","created":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T10:28:05Z","timestamp":1790764085000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Mechanochemical Activation of Biodegradable High\u2010Entropy Materials Enables Immune\u2010Synergistic Therapy for Deep\u2010Seated and Drug\u2010Resistant Infections"],"prefix":"10.1002","author":[{"given":"Die","family":"Yu","sequence":"first","affiliation":[{"name":"Zhejiang Key Laboratory of Ophthalmic Drug Discovery and Medical Device Research Eye Hospital Wenzhou Medical University  Wenzhou China"},{"name":"Department of Otolaryngology The First 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Southeast University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hailin","family":"Xie","sequence":"additional","affiliation":[{"name":"Zhejiang Key Laboratory of Ophthalmic Drug Discovery and Medical Device Research Eye Hospital Wenzhou Medical University  Wenzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian","family":"Liu","sequence":"additional","affiliation":[{"name":"Zhejiang Key Laboratory of Ophthalmic Drug Discovery and Medical Device Research Eye Hospital Wenzhou Medical University  Wenzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zi\u2010Tong","family":"Wu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Marine Chemistry Theory and Technology, and College of Chemistry and Chemical Engineering, Ministry of Education Ocean University of China  Qingdao 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