Enzyme‐Responsive Nanoparticles for Targeted Accumulation and Prolonged Retention in Heart Tissue after Myocardial Infarction

Herein, we describe a method for targeting to and retaining intravenously (IV) injected nanoparticles at the site of acute myocardial infarction (MI) in a rat model. Enzyme-responsive peptide-polymer amphiphiles (PPAs) were prepared and assembled as spherical micellar nanoparticles. The resulting nanoparticles respond to matrix metalloproteineases (MMP-2 and MMP-9) that are upregulated in heart tissue post-myocardial infarction. The nanoparticles undergo a morphological transition from spherical-shaped, discrete materials to network-like assemblies when acted upon by MMPs. We show that 15–20 nm, responsive nanoparticles can be injected IV, undergoing reaction with MMPs in the heart after MI, with the resulting assemblies remaining within the infarct for up to 28 days. The initial studies reported here set the stage for the development of targeting systems for therapeutic delivery for acute MI. Critically, with this development, injection of materials is possible via the IV route immediately following MI, resulting in targeted accumulation and long term retention at the site of MI.