Lipid droplet–enriched luminogens enable adoptive macrophage transfer for treatment of bacterial sepsis

Bacterial sepsis, a life-threatening systemic inflammatory response to infection affecting over 30 million people annually, is exacerbated by antibiotic resistance and immune suppression. Here, we report a small luminescent molecule, TPA2PyPh, as a potent antibacterial agent and its potential for lipid droplet-engineered macrophage transfer strategy in treating bacterial sepsis. 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-engineered macrophage transfer as an effective approach for treating sepsis and managing severe infectious diseases.