Development of a Delivery Platform for Protein-Based Regenerative and Reparative Cardiac Therapies

Cell-based therapies for heart failure have been investigated in the field of regenerative medicine, however recent discoveries have shown that cardiac progenitor-cell derived paracrine effects (the secretome) may be inducing endogenous repair, instead of an intrinsic benefit from the stem cells themselves. We hypothesize that polyurethane-based nanoparticles will enable the delivery of therapeutic components of neonatal cardiac progenitor cell secretomes (BMP-4 and Ang1-7) and will induce characteristics representative of repair in damaged heart tissue. Polyurethane-based nanoparticles with a diameter of 190 ± 2 nm (polydispersity index < 0.2) and a zeta potential of -40 ± 1 mV were generated through an emulsion inversion technique. Through optimization of the concentration, coating duration, and coating efficiency, BMP-4 and Ang1-7 were coated onto the surface of the nanoparticles. Treatment with the coated nanoparticles significantly reduced expression of senescence associated b-galactosidase, a marker for senescence which is an important contributor to heart failure. On-going future work will further investigate the biological function of the nanoparticles with their biological payload, characterize both the particle and the biomolecule stabilities, and investigate co-delivery of multiple biomolecules simultaneously, in both in vitro cardiac cell and in vivo heart tissue models.