Targeted suppression of CCR7/NF-κB signaling by apoptotic body-inspired colchicine nanovesicles halts atherosclerotic progression.

Atherosclerosis (AS) is a chronic inflammatory disorder characterized by foam cell formation and persistent inflammation as central pathological drivers. Although colchicine (Col) exhibits potent anti-inflammatory activities, its clinical application is limited by a narrow therapeutic window. In the present study, we developed phosphatidylserine-exposing nanovesicles (Col@PSVs) that leverage the innate phagocytic capacity of macrophage-derived foam cells by presenting surface "eat-me" signals, thereby enabling targeted immune modulation. The synergistic collaboration between Col and PSVs allows low-dose Col to retain robust anti-inflammatory efficacy while mitigating dose-dependent toxicity. Mechanistically, Col@PSVs potently suppress CCR7-mediated NF-κB signaling activation in foam cells, leading to a marked downregulation of pro-inflammatory cytokine and disruption of inflammatory cascades. In ApoE-/- AS mouse models, Col@PSVs treatment significantly improved plaque stability and attenuated disease progression. These findings highlight the pivotal role of the CCR7/NF-κB signaling pathway in AS-associated inflammation and present a translational nanotherapeutic strategy with the potential to overcome the clinical limitations of Col.