Heart failure following myocardial infarction (MI) is a leading cause of deaths in US. MI triggers ischemic necrosis of cardiomyocytes, and initiates a chain of inflammatory responses, which lead to negative left ventricular (LV) remodeling and compromised cardiac function. Although injectable biomaterials have been extensively studied as the potential treatment for MI, a majority of them suffers from limited delivery method and fast cardiac clearance, which restrain their applications in acute MI (AMI). Previously, our group developed an intravenous injectable peptide-polynorbornene amphiphile based nanoparticle that was shown to target and be retained in the infarct up to 28 days in response to the overexpressed matrix metalloproteinases (MMPs) post AMI. As the nanoparticles reach the infarct through the leaky vasculature, the upregulated MMPs cleave the peptide corona, triggering the formation of micron size aggregates for long-term retention. MMPs have also been demonstrated as the major contributor to the adverse LV remodeling in literature. Herein, we showed that the nanoparticles can be deployed as a delivery vehicle for a small molecule MMP inhibitor. By conjugating the inhibitor on the polymer backbone via a hydrolytically labile ester bond, we achieved targeted MMP inhibitor delivery to the infarct. Based on the result from the rat AMI model, our material showed prolonged retention in the infract (six days post intravenous injection) and significantly decreased cardiac MMP level. The impact of nanoparticle treatment on cardiac function is currently under investigation.

Enzyme-responsive nanoparticles for targeted drug delivery to the heart post-myocardial infarction

Macromolecular Chemistry: The Second Century

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ACS Spring 2020 National Meeting & Expo

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.