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Herein, this study presents an innovative method involving the synthesis of three furoxan derivatives engineered to self\u2010assemble into nitric oxide (NO) donor nanoparticles (FuNPs). These FuNPs, notably supplied together with polymyxin B (PMB), achieve markedly enhanced bactericidal efficacy against a wide spectrum of bacterial phenotypes at considerably lower NO concentrations (0.1\u20132.8\u00a0\u00b5g\u00a0mL\n                    <jats:sup>\u22121<\/jats:sup>\n                    ), which is at least ten times lower than the reported data for NO donors (\u2265200\u00a0\u00b5g\u00a0mL\n                    <jats:sup>\u22121<\/jats:sup>\n                    ). The bactericidal mechanism is elucidated using confocal, scanning, and transmission electron microscopy techniques. Neutron reflectometry confirms that FuNPs initiate membrane disruption by specifically engaging with the polysaccharides on bacterial surfaces, causing structural perturbations. Subsequently, PMB binds to lipid A on the outer membrane, enhancing permeability and resulting in a synergistic bactericidal action with FuNPs. This pioneering strategy underscores the utility of self\u2010assembly in NO delivery as a groundbreaking paradigm to circumvent traditional antibiotic resistance barriers, marking a significant leap forward in the development of next\u2010generation antimicrobial agents.\n                  <\/jats:p>","DOI":"10.1002\/adhm.202403046","type":"journal-article","created":{"date-parts":[[2024,9,12]],"date-time":"2024-09-12T08:23:33Z","timestamp":1726129413000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Enhanced Nitric Oxide Delivery Through Self\u2010Assembling Nanoparticles for Eradicating Gram\u2010Negative Bacteria"],"prefix":"10.1002","volume":"13","author":[{"given":"Xiangfeng","family":"Lai","sequence":"first","affiliation":[{"name":"Department of Materials Science and Engineering Faculty of Engineering Monash University  Clayton Victoria 3800 Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Yu","sequence":"additional","affiliation":[{"name":"School of Chemistry Monash University  Clayton VIC 3800 Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiangyi","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Materials Science and Engineering Faculty of Engineering Monash University  Clayton Victoria 3800 Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wil","family":"Gardner","sequence":"additional","affiliation":[{"name":"Centre for Materials and Surface Science and Department of Mathematical and Physical Sciences La Trobe University  Bundoora 3086 Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah E.","family":"Bamford","sequence":"additional","affiliation":[{"name":"Centre for Materials and Surface Science and Department of Mathematical and Physical Sciences La Trobe University  Bundoora 3086 Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul J.","family":"Pigram","sequence":"additional","affiliation":[{"name":"Centre for Materials and Surface Science and Department of Mathematical and Physical Sciences La Trobe University  Bundoora 3086 Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuhong","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Materials Science and Engineering Faculty of Engineering Monash University  Clayton Victoria 3800 Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anton P. Le","family":"Brun","sequence":"additional","affiliation":[{"name":"Australian Centre for Neutron Scattering Australian Nuclear Science and Technology Organisation  Lucas Heights NSW 2232 Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin W.","family":"Muir","sequence":"additional","affiliation":[{"name":"CSIRO Manufacturing  Clayton VIC 3168 Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiangning","family":"Song","sequence":"additional","affiliation":[{"name":"Infection and Immunity Program Monash Biomedicine Discovery Institute and Department of Microbiology Monash University  Clayton VIC 3800 Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yajun","family":"Wang","sequence":"additional","affiliation":[{"name":"College of Chemistry &amp; Materials Engineering Wenzhou University  Shanghai Wenzhou 325027 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