Abstract
Cardiovascular disease is the leading cause of mortality worldwide. Atherosclerosis, one of the most common forms of the disease, is characterized by a gradual formation of atherosclerotic plaque, hardening, and narrowing of the arteries. Nanomaterials can serve as powerful delivery platforms for atherosclerosis treatment. However, their therapeutic efficacy is substantially limited in vivo due to nonspecific clearance by the mononuclear phagocytic system. In order to address this limitation, rapamycin (RAP)-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles are cloaked with the cell membrane of red blood cells (RBCs), creating superior nanocomplexes with a highly complex functionalized bio-interface. The resulting biomimetic nanocomplexes exhibit a well-defined "core-shell" structure with favorable hydrodynamic size and negative surface charge. More importantly, the biomimetic nature of the RBC interface results in less macrophage-mediated phagocytosis in the blood and enhanced accumulation of nanoparticles in the established atherosclerotic plaques, thereby achieving targeted drug release. The biomimetic nanocomplexes significantly attenuate the progression of atherosclerosis. Additionally, the biomimetic nanotherapy approach also displays favorable safety properties. Overall, this study demonstrates the therapeutic advantages of biomimetic nanotherapy for atherosclerosis treatment, which holds considerable promise as a new generation of drug delivery system for safe and efficient management of atherosclerosis.