Cardiac targeted delivery of Maresin 1 nanomedicine rescues microvascular obstruction after myocardial infarction

Microvascular obstruction (MVO) is recognized as an independent risk factor for adverse prognosis in patients with myocardial infarction (MI), and its development is mechanistically linked to inflammation and microthrombus. Maresin 1 (MaR1), a specialized pro-resolving mediator, has demonstrated therapeutic potential in counteracting these processes, but its translation has been hindered by poor stability and rapid degradation. To overcome these limitations, we report the development of a cardiac-targeted liposomal nanotherapeutic (nano-MaR1) designed to stabilize and selectively deliver MaR1 to the injured myocardium. Nano-MaR1 was generated through a scalable nanoprecipitation method in a herringbone microfluidic mixer, with MaR1 encapsulated by a freeze–thaw approach to minimize degradation, and further modified with a cardiac-homing peptide for organ-specific targeting. In a murine MI model, intravenous administration of nano-MaR1 led to rapid myocardial enrichment within 12 h, with 20 μM identified as the optimal therapeutic dose. Treatment markedly reduced infarct size, cardiomyocyte apoptosis, inflammatory infiltration, and MVO formation, while promoting reparative macrophage polarization toward the M2 phenotype. Mechanistic studies revealed that these effects were mediated by downregulation of Itgam (CD11b) within the coagulation cascade and inhibition of monocyte–platelet aggregate formation, which were abolished upon CD11b blockade. Collectively, this work establishes cardiac-targeted liposomal encapsulation as a powerful strategy to enhance the stability and bioactivity of MaR1, and highlights nano-MaR1 as a promising therapeutic candidate for mitigating MVO and improving post-MI repair.