Artificial lipids and macrophage membranes coassembled biomimetic nanovesicles for thoracic aortic dissection treatment

Thoracic aortic dissection (TAD) is a life-threatening cardiovascular disease characterized by rapid progression and high morbidity. Current efforts to develop effective treatment strategies focus on targeting apoptotic aortic endothelial cells and mitigating inflammation. Here, inspired by the inflammation-neutralizing capacity of functional cells, we present multifunctional biomimetic nanovesicles (MM-LPs) co-assembled from macrophage membranes and synthetic lipids for the targeted delivery of Senkyunolide I (SEI) in TAD treatment. The integration of macrophage membranes endows MM-LPs with the ability to selectively target activated vascular endothelial cells (VECs) while adsorbing proinflammatory cytokines to suppress inflammation. Additionally, these nanoparticles enable the controlled release of SEI, leading to significant anti-apoptotic effects. Leveraging these advantages, MM-LPs effectively mitigated VEC activation, reduced apoptosis, and prevented disease progression and rupture in a BAPN-induced mouse model of TAD. Furthermore, this system significantly reduced SEI-associated toxicity and adverse effects on the liver and kidneys. These findings highlight the potential of combining natural macrophage membranes with synthetic lipids to develop a multifunctional biomimetic drug delivery system for treating VEC dysfunction while minimizing drug-related side effects.