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Since the speed at which antimicrobial\u2010resistance develops is exceeding the pace at which new antimicrobials come to the market, this threat cannot be countered by making more, new and stronger antimicrobials. Promising new antimicrobials should not only kill antimicrobial\u2010resistant bacteria, but also prevent development of new bacterial resistance mechanisms in strains still susceptible. Here, PAMAM\u2010dendrimers are clustered using glutaraldehyde to form megamers that are core\u2010loaded with ciprofloxacin and functionalized with HA\u2010SNO. Megamers are enzymatically disintegrated in an acidic pH, as in infectious biofilms, yielding release of ciprofloxacin and NO\u2010generation by HA\u2010SNO. NO\u2010generation does not contribute to the killing of planktonic Gram\u2010positive <jats:italic>Staphylococcus aureus<\/jats:italic> and Gram\u2010negative <jats:italic>Pseudomonas aeruginosa<\/jats:italic>, but in a biofilm\u2010mode of growth short\u2010lived NO\u2010assisted killing of both ciprofloxacin\u2010susceptible and ciprofloxacin\u2010resistant bacterial strains by the ciprofloxacin released. Repeated sub\u2010culturing of ciprofloxacin\u2010susceptible bacteria in presence of ciprofloxacin\u2010loaded and HA\u2010SNO functionalized PAMAM\u2010megamers does not result in ciprofloxacin\u2010resistant variants as does repeated culturing in presence of ciprofloxacin. Healing of wounds infected by a ciprofloxacin\u2010resistant <jats:italic>S. aureus<\/jats:italic> variant treated with ciprofloxacin\u2010loaded, HA\u2010SNO functionalized megamers proceed faster through NO\u2010assisted ciprofloxacin killing of infecting bacteria and stimulation of angiogenesis.<\/jats:p>","DOI":"10.1002\/adhm.202301747","type":"journal-article","created":{"date-parts":[[2023,11,1]],"date-time":"2023-11-01T01:44:51Z","timestamp":1698803091000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Ciprofloxacin\u2010Loaded, pH\u2010Responsive PAMAM\u2010Megamers Functionalized with S\u2010Nitrosylated Hyaluronic Acid Support Infected Wound Healing in Mice without Inducing Antibiotic Resistance"],"prefix":"10.1002","volume":"13","author":[{"given":"Guimei","family":"Jiang","sequence":"first","affiliation":[{"name":"Institute of Functional Nano and Soft Materials (FUNSOM) Jiangsu Key Laboratory for Carbon\u2010Based Functional Materials and Devices Soochow University  199 Ren'ai Rd Suzhou Jiangsu 215123 P. 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