Tregs Biomimetic Nanoparticle to Reprogram Inflammatory and Redox Microenvironment in Infarct Tissue to Inhibit the Remodeling of the Left Ventricle of Myocardial Ischemia Reperfusion Injury in Mice

Abstract

Background At present, patients with myocardial infarction remain an increased risk for myocardial ischemia/reperfusion injury (MI/RI), which currently lacks an effective therapeutic method. It is still a bottleneck that effectively deliver drug to ischemic myocardium to treat MI/RI. Inspired by the protective effect of regulatory T cells (Tregs) on MI/RI and natural role of platelets in adhesion with damaged blood vessel in heart during myocardial infarct, a Tregs biomimetic nanoparticle (CsA@PPTK) was prepared by camouflaging a cyclosporin A (CsA)-loaded and reactive oxygen species (ROS)-sensitive nanoparticle with platelet membrane. Results In MI/RI mice, CsA@PPTK could be preferentially delivered to ischemic myocardium. CsA@PPTK significantly scavenged ROS in ischemic myocardium, while it also markedly increased the generation of Tregs and the ratio of M2 type macrophage to M1 type macrophage in ischemic myocardium. Furthermore, CsA@PPTK significantly attenuated apoptosis of cardiomyocytes in ischemic myocardium. At the same time, CsA@PPTK obviously reduced the infarct size, fibrosis area and the protein expression of MMP-9, while increased the protein expression of CX43. Subsequently, the remodeling of the left ventricle was significant alleviated. Finally, heart function of MI/RI mice was markedly improved. Conclusion CsA@PPTK has great potential in the treatment of MI/RI. This study provides a novel class of heart protective biomimetic platform that is beneficial for treatment of MI/RI.