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Hence, novel positively\u2010charged modular nanoparticles (NPs) are developed to load tobramycin (TOB) through a one\u2010step self\u2010assembly method based on metal\u2010phenolic network and Schiff base reaction using 3,4,5\u2010trihydroxybenzaldehyde (THBA), \u03b5\u2010poly\u2010\u029f\u2010lysine (EPL), and Cu<jats:sup>2+<\/jats:sup> as matrix components. In vitro antibacterial test demonstrates that THBA\u2010Cu\u2010TOB NPs exhibit efficient instantaneous sterilization owing to the rapid pH responsiveness to bacterial infections. Notably, only 2.6\u00a0\u00b5g\u00a0mL<jats:sup>\u22121<\/jats:sup> TOP is needed to eradicate <jats:italic>P. aeruginosa<\/jats:italic> biofilm in the nano\u2010formed THBA\u2010Cu\u2010TOB owing to the greatly enhanced penetration, which is only 1.6% the concentration of free TOB (160\u00a0\u00b5g\u00a0mL<jats:sup>\u22121<\/jats:sup>). In animal experiments, THBA\u2010Cu\u2010TOB NPs show significant advantages in ocular surface retention, corneal permeability, rapid sterilization, and inflammation elimination. Based on molecular biology analysis, the toll\u2010like receptor 4 and nuclear factor kappa B signaling pathways are greatly downregulated as well as the reduction of inflammatory cytokines secretions. Such a simple and modular strategy in constructing nano\u2010drug delivery platform offers a new idea for toxicity reduction, physiological barrier penetration, and intelligent drug delivery.<\/jats:p>","DOI":"10.1002\/advs.202309086","type":"journal-article","created":{"date-parts":[[2024,3,16]],"date-time":"2024-03-16T02:22:57Z","timestamp":1710555777000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":38,"title":["An Antibiotic Nanobomb Constructed from pH\u2010Responsive Chemical Bonds in Metal\u2010Phenolic Network Nanoparticles for Biofilm Eradication and Corneal Ulcer Healing"],"prefix":"10.1002","volume":"11","author":[{"given":"Qiang","family":"Gao","sequence":"first","affiliation":[{"name":"National Engineering Research Center of Ophthalmology and Optometry Eye Hospital Wenzhou Medical University  Wenzhou 325000 P. R. 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