Neutrophil Hitchhiking\nEnhances Liposomal Dexamethasone\nTherapy of Sepsis

Sepsis is characterized by a dysregulated immune response\nand is\nvery difficult to treat. In the cecal ligation and puncture (CLP)\nmouse model, we show that nanomedicines can effectively alleviate\nsystemic and local septic events by targeting neutrophils. Specifically,\nby decorating the surface of clinical-stage dexamethasone liposomes\nwith cyclic arginine-glycine-aspartic acid (cRGD) peptides, we promote\ntheir engagement with neutrophils in the systemic circulation, leading\nto their prominent accumulation at primary and secondary sepsis sites.\ncRGD-targeted dexamethasone liposomes potently reduce immature circulating\nneutrophils and neutrophil extracellular traps in intestinal sepsis\ninduction sites and the liver. Additionally, they mitigate inflammatory\ncytokines systemically and locally while preserving systemic IL-10\nlevels, contributing to lower IFN-γ/IL-10 ratios as compared\nto control liposomes and free dexamethasone. Our strategy addresses\nsepsis at the cellular level, illustrating the use of neutrophils\nboth as a therapeutic target and as a chariot for drug delivery.