Engineered erythrocytes for intracellular delivery of therapeutic tools in cardiac hypertrophy models

Cardiac hypertrophy and heart failure are major causes of morbidity and mortality in Western societies. Many factors have been implicated in cardiac remodeling, including alterations in gene expression in cardiomyocyte apoptosis signaling, cytokines and growth factors that influence cardiac dynamics and deficits in energy metabolism, as well as in alterations of cardiac extracellular matrix composition. Among these factors, Birc5-Survivin and Osteopontin seem to play a crucial role in hypertrophic cardiomyocyte signaling. We speculate that their therapeutic targeting could block cardiac remodeling, by inhibiting cardiac fibrosis, apoptosis and autophagy, and alleviate cardiac dysfunction. Within the NANOMAX-ENCODER project, oligonucleotide-based molecules, such as optical-nanosensor Molecular Beacons and siRNAs, able to target the Surivivin and Osteopontin markers, have been developed. Their diagnostic and therapeutic potential has been evaluated both in vitro and in vivo in cardiac hypertrophy models. Furthermore, erythrocyte-based drug delivery system and functionalized nanoparticles have been used in vivo to target unhealthy cardiac cells and to enhance the penetration and transfer of oligonucleotide-based molecules inside target cells. Taken together, the in vitro and in vivo experimental data suggest that Survivin and Osteopontin are effective therapeutic targets to slow disease progression and that target delivery of oligonucleotide-based molecules by engineered erythrocytes could represent a novel promising therapeutic strategy for cardiac hypertrophy.