Engineering metal-organic frameworks as precision nanomedicines for myocardial infarction therapy

Myocardial infarction (MI) remains a major cause of mortality worldwide. However, current therapeutic paradigms are limited in their ability to modulate the post-infarction pathological microenvironment with spatiotemporal precision. Metal-organic frameworks (MOFs), an emerging class of crystalline porous coordination polymers, offer exceptional structural programmability through their ultra-high specific surface areas, tunable pore architectures, and customizable surface chemistries. These properties have positioned MOFs as promising platforms for targeted MI therapy. In this review, the molecular design principles for constructing MOFs as precise nanomedicines for myocardial infarction are examined. Structural strategies-including stimulus-responsive drug delivery, biomimetic nanoplatforms, theranostic systems, and biohybrid constructs-are systematically analyzed with respect to their capacity to modulate the post-infarction microenvironment. The mechanisms underlying MOF-mediated cardiac repair are critically evaluated, with emphasis on oxidative stress regulation, inflammatory microenvironment reprogramming, and angiogenesis promotion. Key translational barriers, including biosafety assessment, scalable manufacturing, delivery-route optimization, and validation in large-animal models, are also discussed. Finally, future directions involving multi-omics-guided architectural design, organ-on-chip technology, 3D-printed cardiac patches, regulatory science, and a testable research agenda are proposed. Although MOF-based MI therapies remain at the preclinical stage, these convergent efforts may accelerate the bench-to-bedside translation of MOF-based precision nanomedicines for cardiovascular disease.