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Conventional therapies often fail to resolve these \u201cdual traps\u201d of structural resistance and immunological interference. Herein, we developed a multifunctional mesoporous nano\u2010regulator composed of Colistin (CT) and m\u2010aminophenol formaldehyde (mAPF) framework, hence termed CT\/mAPF to implement a \u201ctriad\u2010strategy\u201d: biofilm disruption, bacterial eradication, and debris neutralization. The CT\/mAPF nano\u2010regulator achieves potent bactericidal activity (99.99%) and initiates ROS\u2010mediated oxidative fragmentation of eDNA to destroy the biofilm scaffold. Crucially, the platform effectively neutralizes LPS and degrades eDNA, leading to the simultaneous silencing of TLR4 and TLR9 signaling pathways. This dual\u2010targeting approach weakens the eDNA\/LPS\u2010mediated synergistic inflammatory response, and suppresses pro\u2010inflammatory cytokines (\n                    <jats:italic>IL\u20106<\/jats:italic>\n                    ,\n                    <jats:italic>IL\u20101\u03b2<\/jats:italic>\n                    ,\n                    <jats:italic>TNF\u2010\u03b1<\/jats:italic>\n                    ). In diabetic mouse models, CT\/mAPF significantly accelerated bacterial clearance and wound closure through enhanced angiogenesis and collagen maturation. This integrated strategy resolves the cycle of chronic infection and inflammation, offering a robust strategy for Gram\u2010negative bacteria\u2010infected diabetic wound management.\n                  <\/jats:p>","DOI":"10.1002\/advs.76300","type":"journal-article","created":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T12:31:57Z","timestamp":1782477117000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Mesoporous Catalytic\u2010Adsorptive Nanoregulator Orchestrates Biofilm eDNA\/LPS Disassembly and TLR9\/TLR4 Immune Reprogramming to Resolve Diabetic Foot Infections"],"prefix":"10.1002","volume":"13","author":[{"given":"Junfeng","family":"Song","sequence":"first","affiliation":[{"name":"Lab of Advanced Materials, College of Smart Materials and Future Energy, Department of Chemistry Fudan University  Shanghai 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Future Energy, Department of Chemistry Fudan University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yixiang","family":"Wang","sequence":"additional","affiliation":[{"name":"Lab of Advanced Materials, College of Smart Materials and Future Energy, Department of Chemistry Fudan University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianbao","family":"Zhu","sequence":"additional","affiliation":[{"name":"Lab of Advanced Materials, College of Smart Materials and Future Energy, Department of Chemistry Fudan University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6056-6928","authenticated-orcid":false,"given":"Xiaomin","family":"Li","sequence":"additional","affiliation":[{"name":"Lab of Advanced Materials, College of Smart Materials and Future Energy, Department of Chemistry Fudan University  Shanghai 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