An apoptotic body-biomimic liposome in situ upregulates anti-inflammatory macrophages for stabilization of atherosclerotic plaques.

The macrophages mediated inflammation participates in every stage of atherosclerosis. Attenuation of macrophages inflammatory responses by active ingredients in atherosclerotic plaques is benefit to atherosclerotic stabilization and regression, but meanwhile, it is highly desired to develop accurate therapeutics for reducing off-target effects. Previous studies revealed that the apoptotic bodies are effectively recognized and engulfed by macrophages own to increased exposure of phosphatidylserine (PtdSer), which is regarded as a key "eat-me" signal. To achieve optimal delivery efficiency, an apoptotic body biomimic liposome (AP-Lipo) is constructed by decorating PtdSer and DSPE-PEG2000-cRGDfK onto the surface of liposome for selectively delivering pioglitazone (PIO), a peroxisome proliferator-activated receptor γ (PPARγ) agonist, into atherosclerotic macrophages while minimizing its side effects. Compared with unmodified liposome, AP-Lipo is more effective to recognize and penetrate the activated vascular endothelial monolayer, target pro-inflammatory macrophages and suppress the inflammation by upreglation of anti-inflammatory cytokines in vitro. Moreover, AP-Lipo can effectively target to atherosclerotic plaques and imped the progression of atherosclerosis by upregulating anti-inflammatory macrophages number and stabilizing the atherosclerotic plaques. In summary, this design imitates the characteristic of apoptotic body and provides a potential drug delivery system for atherosclerosis and other diseases, which attribute to inflammation mediated by macrophages.