ACS Nano 12, 7826–7837 (2018)

Myocardial infarction is caused by formation of a thrombus that occludes the blood vessels, interrupting the blood flow to the heart with subsequent ischaemic damage. A first line of treatment consists in administration of anticoagulant drugs to dissolve the aggregated fibrin in the thrombus and re-establish blood flow. But a sudden rush of blood to the heart can result in ischaemic reperfusion injury and cardiac fibrosis.

Mihalko and collaborators present a fibrin-targeted nanogel that releases tissue plasminogel activator (tPA), for blood thinning, and Y-27632, a small drug that inhibits the cellular mechanisms underlying fibrosis. The nanogel is composed of a polymeric mesh of different densities, with a highly cross-linked core entrapping the smaller molecule and a looser shell encapsulating tPA. This architecture enables release of tPA for clot dissolution, followed by delivery of Y-27632. Upon injection in animal models, the nanogel targets the damaged heart with little accumulation in other organs and leads to improved cardiac functions, measured in terms of increased left ventricular ejection fractions, diminished fibrin deposition and reduced scar-tissue formation.