Following a myocardial infarction (MI), heart failure remains a significant burden for patients worldwide. As the cardiomyocytes in the infarct region undergo apoptosis, the surrounding extracellular matrix begins to degrade, leading to negative left ventricular remodeling and dysfunction. The design of biomaterials for non-invasive, acute MI treatment is ideal for inhibiting cell death, and to restore cardiac function. Polymeric nanoparticles can be delivered via intravenous (IV) injection and targeted to the damaged cardiac tissue through the enhanced permeability and retention (EPR) effect, making them promising candidates for minimally invasive, acute MI treatment methods. Here, a class of biodegradable, poly(lactone)-based amphiphilic block copolymers, functionalized with an enzyme responsive peptide, were synthesized for the formation of a nanoparticle delivery system to the infarcted tissue. Following cleavage of the hydrophilic peptide by inflammatory enzymes, matrix metalloproteinase (MMP)-2/9, the hydrophobicity of the remaining polymeric structure causes assemblies of aggregates that are retained in the infarcted tissue. Gradual clearance from the body results as the polymeric unit degrades. Concurrently, these nanoparticle systems can be functionalized with a therapeutic peptide, affording a non-invasive, slow release MI treatment that can be delivered as acutely as possible to repair and treat damaged cardiac tissue.

Biodegradable, enzyme-responsive nanoparticles for acute myocardial infarction

253rd National Meeting (2017)

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