Acute myocardial infarction (MI) causes tremendous damage to the coronary microcirculation, resulting in vascular disintegration and capillary rarefaction in the infarct area. Tissue repair after myocardial infarction (MI) is multifaceted. The mechanism of angiogenesis is complex and difficult to target, and the blood vessels that need to be revascularized extend from the infarct border zone to the necrotic infarct core ¹ . Mirdametinib (PD0325901), a MEK inhibitor, promotes angiogenesis and has beneficial effects on ischemic hearts. However, its side effects have limited its application, and Mirdametinib has not yet met clinical requirements for how to treat diseases more safely, effectively and economically. Here, we present a multifunctional biomimetic nanoparticle drug delivery system consisting of Macrophage Membranes and Liposomes nanoparticles (MM & Lipo nanoparticles) for the targeted delivery of Mirdametinib (PD0325901) to induce ischemic tissue revascularization after acute MI. Compared with artificial liposomes, the MM & Lipo nanoparticle delivery system has the advantages of immune escape and strong activation of endothelial cell targeting. Additionally, MM & Lipo nanoparticles release sufficient PD0325901 in a controlled manner. In an induced MI model, it significantly improved cardiac function and infarct extent in mice. Compared with the PBS group after MI, the ejection fraction of MM & Lipo group recovered from 35 ± 3–82 ± 3, and the fractional shortening from 17 ± 2–50 ± 1. The area of fibrosis was also reduced from 25 ± 4 % to 11 ± 5. The key inflammatory factor marker TNF-α also decreased from 570 ± 31 pg/mL to 475 ± 70 pg/mL.Our findings demonstrate the important potential value of multifunctional biomimetic drug delivery systems that integrate macrophage membranes and liposomes as novel membrane materials in the treatment of post-MI revascularization.