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Herein, we designed and synthesized functional diethylenetriaminepentaacetic acid\u2013spermidine carbon dots (D\u2010CDs), which exerted dual antibacterial and immunomodulatory effects by targeting iron metabolism. D\u2010CDs exhibited high affinity for Fe\n                    <jats:sup>3+<\/jats:sup>\n                    , effectively chelating Fe\n                    <jats:sup>3+<\/jats:sup>\n                    to induce \u201ciron starvation\u201d in bacteria, leading to metabolic disruption and increased oxidative stress, as evidenced by altered expression of gene associated with iron acquisition, energy metabolism, and oxidative stress defense. Furthermore, D\u2010CDs displayed potent antibacterial activity against bacteria containing clinical isolated resistant strains. Concurrently, D\u2010CDs protected host macrophages by attenuating ferroptosis through activation of the Nrf2\/HMOX1 pathway and inhibition of the NF\u2010\u03baB pathway, thereby restoring redox balance and promoting polarization toward the anti\u2010inflammatory M2 phenotype. In the two rat models of sepsis, induced by intravenous administration of bacterial suspension and by cecal ligation and puncture, D\u2010CDs significantly improved survival rates, reduced systemic bacterial burden, and alleviated multi\u2010organ inflammatory injury. Taken together, these findings suggest that iron metabolism centered modulation as a dual\u2010targeting strategy possess brilliant future for treating severe bacterial infections through integrating antibacterial action with immune homeostasis.\n                  <\/jats:p>","DOI":"10.1002\/smll.76147","type":"journal-article","created":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T16:34:32Z","timestamp":1791477272000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Iron\u2010Metabolism\u2013Modulating Carbon Dots Controllably Orchestrates Antibacterial and Immunoregulatory Synergy for Effective Bacterial Sepsis Therapy"],"prefix":"10.1002","author":[{"given":"Yao","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Analysis School of Pharmacy Fujian Medical University  Fuzhou China"},{"name":"Department of Pharmacy Fujian Medical University Union Hospital  Fuzhou 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