Nano-pathogenoids hitchhike activated neutrophils for eliminating of atherosclerosis plaques

Atherosclerosis (AS) is a chronic inflammatory disease characterized by plaques that are difficult to eliminate. Neutrophil extracellular traps (NETs) are a central factor in the progression of AS, which could trigger a cascade of inflammatory reactions and increase plaque volume. Focusing on inhibiting the release of NETs within plaques is beneficial for erasing plaques. However, the arterial stenosis and poor blood flow caused by plaques prevent most therapeutic agents from entering the AS lesions. Considering that activated neutrophils firstly migrate to the interior of plaques after being stimulated by cytokines, we proposed a strategy based on bacteria-derived outer-membrane vesicles (OMVs) to hitchhike activated neutrophils for enhancing AS plaques delivery of therapeutic agents to treat AS. DNase Ⅰ and atorvastatin (At) were encapsulated into OMVs to prepare OMV@DAt nanoparticles, which could be specifically internalized by activated neutrophils in blood circulation by inheriting analogous functions to the bacterial outer-membrane. Neutrophils endocytosed OMV@DAt could infiltrate into the AS plaques to boost drugs concentrations. OMV@DAt was certified to significantly degrade NETs from neutrophils and inhibit the expression of CD47 in apoptotic cells, which could further alleviate the inflammatory response, enhance the clearance of lipid necrotic cores by macrophages, and ultimately promote plaque regression.