Targeting fibrosis in the failing heart with nanoparticles.

Abstract Heart failure (HF) is a clinical syndrome characterized by typical symptoms and signs caused by a structural and/or functional cardiac abnormality, resulting in a reduced cardiac output and/or elevated intracardiac pressures at rest or during stress. Due to increasing incidence, prevalence and, most importantly mortality, HF is a healthcare burden worldwide, despite the improvement of treatment options and effectiveness. Acute and chronic cardiac injuries trigger the activation of neurohormonal, inflammatory, and mechanical pathways ultimately leading to fibrosis, which plays a key role in the development of cardiac dysfunction and HF. The use of nanoparticles for targeted drug delivery would greatly improve therapeutic options to identify, prevent and treat cardiac fibrosis. In this review we will highlight the mechanisms of cardiac fibrosis development to depict the pathophysiological features for passive and active targeting of acute and chronic cardiac fibrosis with nanoparticles. Then we will discuss how cardiomyocytes, immune and inflammatory cells, fibroblasts and extracellular matrix can be targeted with nanoparticles to prevent or restore cardiac dysfunction and to improve the molecular imaging of cardiac fibrosis.