Monocytes: a novel drug delivery system targeting atherosclerosis

摘要

Scavenging of reactive oxygen species (ROS) by antioxidants holds great promise to alleviate the symptoms of cardiovascular diseases and atherosclerosis. In atherosclerosis, damaged endothelial cells (EC) generate more ROS and inflammatory mediators, which recruit more monocytes to the EC. Antioxidants are good therapeutic drug candidates; however, antioxidant enzymes such as catalase are easily degraded by proteases in vivo and chemical mimetics of superoxide dismutase such as tempol and tempo require a target-specific delivery system since hydrophobic tempol or tempo can diffuse into any type of cells non-specifically. Here, we report a novel monocyte-based drug delivery system encapsulating either catalase or tempol/tempo. Monocyte as a novel drug delivery vehicle offers advantages over other delivery systems due to its target specificity to damaged EC. The delivery system can also be easily fabricated in biological conditions and keeps antioxidants active. Membrane impermeable catalase with protease inhibitors was formulated in monocytes via a hypotonic/resealing method and membrane permeable tempol/tempo were encapsulated in monocytes via passive diffusion with 40-60% encapsulation efficiency. Antioxidant-loaded monocytes targeted EC and the antioxidants scavenged more than 90% intracellular ROS generated by cytokines or exogenous ROS. We anticipate numerous applications of the monocyte-based drug delivery system, given its target specificity to activated EC.