Sprayable macrophage-targeting apoptotic-body-inspired nanotherapeutics for the prevention of postoperative peritoneal adhesions.

Postoperative peritoneal adhesion is a common complication of abdominal and pelvic surgeries, often leading to chronic pain, bowel obstruction, and increased reoperation rates. Despite clinical efforts, effective preventive strategies remain limited. In this study, we develope a sprayable, biomimetic nanotherapeutic system - designated Apo-Q - composed of phosphatidylserine (PS)-exposing liposomes encapsulating quercetin (Que@PSLs), inspired by the biological features of apoptotic bodies and prepared by a thin-film hydration-extrusion method. The obtained Apo-Q with the particle size about 140 nm and PS-functionalized surface can be selectively recognized and internalized by macrophages, thereby promoting targeted modulation of the postoperative inflammatory microenvironment. In a mouse model of peritoneal adhesion, Apo-Q promotes macrophage polarization from the pro-inflammatory M1 phenotype to the reparative M2 phenotype, suppresses inflammatory response, and also prevents pathological accumulation of GATA6+ macrophages at injury sites, significantly reducing adhesion formation and severity. These findings demonstrate that Apo-Q exerts potent anti-inflammatory and anti-fibrotic effects probably via a similar mechanism to macrophage efferocytosis, offering a minimally invasive and translationally promising strategy for preventing postoperative peritoneal adhesions.