Targeted delivery and ROS-responsive release of Resolvin D1 by platelet chimeric liposome ameliorates myocardial ischemia–reperfusion injury

Abstract

Resolvin D1 (RvD1) has been shown to provide effective protection against ischemia–reperfusion injury in multiple vital organs such as the heart, brain, kidney. However, the clinical translational potential of systemic administration of RvD1 in the treatment of ischemia–reperfusion injury is greatly limited due to biological instability and lack of targeting ability. Combining the natural inflammatory response and reactive oxygen species (ROS) overproduction after reperfusion injury, we developed a platelet-bionic, ROS-responsive RvD1 delivery platform. The resulting formulation enables targeted delivery of RvD1 to the injury site by hijacking circulating chemotactic monocytes, while achieving locally controlled release. In a mouse model of myocardial ischemia repefusuin (MI/R) injury, intravenous injection of our formula resulted in the enrichment of RvD1 in the injured area, which in turn promotes clearance of dead cells, production of specialized proresolving mediators (SPMs), and angiogenesis during injury repair, effectively improving cardiac function. This delivery system integrates drug bio-protection, targeted delivery and controlled release, which endow it with great clinical translational value.