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Engineered macrophages, created by directly incubating TPA2PyPh with macrophages, enabled the luminogen to precisely bind to intracellular lipid droplets. Upon engulfment of bacteria, these TPA2PyPh-loaded macrophages use natural lipid uptake mechanisms to deliver the luminogen to intracellular bacteria, disrupting their membranes and inserting into the bacterial DNA, thereby inducing bacterial elimination. Our findings show that the adoptive transfer of TPA2PyPh-loaded macrophages substantially diminishes bacterial burden in septic mice and substantially reduces mortality rates. This study demonstrates the potential of TPA2PyPh as an effective antibacterial agent and supports the use of adoptive lipid droplet\u2013engineered macrophage transfer as an effective approach for treating sepsis and managing severe infectious diseases.<\/jats:p>","DOI":"10.1126\/sciadv.adt8376","type":"journal-article","created":{"date-parts":[[2025,6,6]],"date-time":"2025-06-06T13:58:24Z","timestamp":1749218304000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":8,"title":["Lipid droplet\u2013enriched luminogens enable adoptive macrophage transfer for treatment of bacterial sepsis"],"prefix":"10.1126","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-4998-6893","authenticated-orcid":true,"given":"Xianglong","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Chemical and Biomolecular Engineering, National University of Singapore, 4 Engineering Drive 4, Singapore 117585, 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