Spatiotemporal Nanotherapy After Myocardial Infarction: Targeting the Inflammatory-to-reparative Transition With Extracellular Vesicles and Engineered Nanoparticles.

PURPOSE: Post-myocardial infarction (MI) healing is a moving sequence of injury, inflammatory clearance, resolution, vascular repair, and scar maturation. This review evaluates how extracellular vesicles (EVs), cell-derived nanovesicles, and engineered nanoparticles can be matched to these changing biological requirements. METHODS: A critical narrative synthesis was organized around four approximate post-MI windows: minutes to 24 h, days 1-3, days 3-7, and after day 7. Representative mechanistic, rodent, porcine, and human studies were compared by target cell, cargo, material, release profile, route, quantitative delivery evidence, efficacy, and translational liability. RESULTS: Early oxidative and microvascular injury favors brief cytoprotection and vascular targeting; the inflammatory peak favors calibrated control of recruited leukocytes while preserving debris removal; resolution favors efferocytosis, reparative immune signaling, angiogenesis, and local immunomodulation; and later remodeling favors selective rather than global antifibrotic therapy. Directly generated nanovesicles and modified-mRNA lipid nanoparticles expand the design space. However, human evidence remains sparse, and most preclinical studies use fixed schedules, young non-comorbid rodents, qualitative biodistribution, and incompletely defined potency assays. CONCLUSION: A credible spatiotemporal product must demonstrate phase-dependent target availability, controlled exposure, target-cell cargo engagement, and reduced benefit or emerging harm with a deliberately mismatched schedule. Translation requires quantitative pharmacokinetics and biodistribution, route-specific safety, mechanism-linked potency, scalable manufacturing, and validation in reperfused comorbid large-animal models.