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Such DFU lesions often experience delayed recovery, primarily due to the bacteria\u2010induced inflammation in the adverse diabetic microenvironment. Here, an endogenous adenosine triphosphate (ATP)\u2010responsive hydrogel prodrug platform (abbreviated as HSAQ3), which embeds hemoglobin@zeolitic imidazolate framework\u20108 (Hb@ZIF\u20108) nanoparticles in a prodrug (1\u2010naphthylacetic acid, NAA)\u2010loaded biopolymer matrix, targeting multidrug\u2010resistant bacterial infections in DFUs is presented. Initially, using a simple local injection, an HSAQ3 adhesive barrier triggered by UV light is applied to the wound. Concurrently, HSAQ3's composition, enriched with quaternary ammonium salt and phenylboronic acid groups, exhibits strong bacterial trapping capabilities, effectively capturing bacteria at the wound location within the hydrogel. Following this, ATP secreted by bacteria initiates the degradation of Hb@ZIF\u20108, enabling the simultaneous interaction of the encapsulated NAA prodrug with Hb peroxidase. This process effectively produces reactive oxygen species (ROS) in situ, addressing their limited lifespan and diffusion range, thus guaranteeing a highly efficient bactericidal effect. This study unveils an innovative inorganic\u2013organic hybrid prodrug system, leveraging endogenous ATP from bacteria for precise ROS generation, enhancing the healing of multidrug\u2010resistant bacterial infections in DFUs.<\/jats:p>","DOI":"10.1002\/adhm.202500688","type":"journal-article","created":{"date-parts":[[2025,6,10]],"date-time":"2025-06-10T09:58:14Z","timestamp":1749549494000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["An Endogenous Adenosine Triphosphate\u2010Activated Hydrogel Prodrug System for Healing Multidrug\u2010Resistant Bacteria Infected Diabetic Foot Ulcers"],"prefix":"10.1002","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2480-7242","authenticated-orcid":false,"given":"Xiaoliang","family":"Qi","sequence":"first","affiliation":[{"name":"National Engineering Research Center of Ophthalmology and Optometry Eye Hospital Wenzhou Medical University  Wenzhou Zhejiang 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