Abstract

Aortic dissection (AD) is a life-threatening disease featured by the dissection of intimal layer and the formation of a blood-filled false lumen within the aortic wall. Recent studies revealed that the formation and progression of AD lesions is closely related to vascular inflammation and macrophage infiltration . However, the potential efficacy of anti-inflammatory therapy on the prevention and treatment of AD has not been extensively investigated. Herein, we proposed a biomimetic anti-inflammatory liposome (PM/TN-CCLP) co-loaded with curcumin and celecoxib (CC), modified with cell-penetrating TAT-NBD fusion peptide (TN), and further camouflaged by isolated macrophage plasma membrane (PM), as a potential nanotherapy for AD. In vitro results showed that PM/TN-CCLP exhibited low cytotoxicity and elevated cellular uptake by inflammatory macrophages, and prominently inhibited the transendothelial migration, inflammatory responses and ROS generation of macrophages. Moreover, the PM/TN-CCLP treatment significantly prevented the H 2 O 2 -induced smooth muscle cell apoptosis . In vivo experiments were performed on the acute and chronic AD mouse models, respectively. The results verified the elevated accumulation of PM-camouflaged liposome at the aorta lesions. Further, the anti-inflammatory liposomes, especially PM/TN-CCLP, could reduce the rupture rate of dissection, prevent the loss of elastic fibers, and reduce MMP-9 expression as well as macrophage infiltration in the aortic lesions. Notably, as compared with free drugs and TN-CCLP, the PM/TN-CCLP treatment displayed the longest survival period along with the minimal aortic injury on both acute and chronic AD mice. Taken together, the present study suggested that the macrophage-biomimetic anti-inflammatory nanotherapy would be a promising strategy for the prevention and therapy of aortic dissection.