Tunable regional targeting of self-assembling peptide nanomaterials in acute myocardial infarction

Acute myocardial infarction (AMI) causes cardiac tissue damage and creates a transient leaky vasculature, which is an attractive target for intravascular therapeutics. Nanomaterials have the potential to deliver therapeutics to the injured heart, yet the influence of particle size, shape, and surface decoration on infarct localization has not been systematically examined. Here, we evaluated a self-assembling peptide platform that can be tuned to form high aspect ratio nanofibers or globular nanoparticles by modifying the β sheet forming domain. This platform has tunable nanofiber length distribution via sonication and aging as well as surface decoration via targeting peptides. In a rat model of AMI, the incorporation of a type IV collagen targeting peptides significantly increased localization of the nanofibers to the injured leaky vasculature while globular peptides diffuse through and targeted the infarcted myocardium. These results demonstrate that this modular peptide nanomaterial can be tuned via geometry and surface moieties to either target to the compromised vasculature components or infiltrate the infarct. This study establishes size, shape, and surface decoration as critical features for effective intravascular nanomaterial delivery after AMI.