(P018) ON-THE-SPOT NANOSPRAY PEPTIDE-GOLD FORMULATION FOR MYOCARDIAL INFARCTION TREATMENT

Background: Despite the progress of cardiac treatments over the last decades, the prevalence of heart failure is on the rise. While interventional procedures can restore blood supply after myocardial infarction, patients who do not have immediate access or do not respond adequately to such procedures are at higher risk to develop heart failure. We present a nano-spray therapy for on-the spot-repair of a heart attack. Our sprayable therapy uses nano-engineered peptide-based materials, where nanomolar concentrations of surface engineered spherical nanogold are used to coat the surface of the cardiac muscle. The spray-on treatment was applied in a clinically relevant mouse myocardial infarction model at the delayed heart attack effects which is a prime opportunity to intervene to limit pathological cardiac remodelling and promote infarct repair.

METHODS AND RESULTS: Here, we conducted a study to (i) develop custom-made peptides for stabilizing and anchoring nanogold to the cardiac muscle; (ii) design a sprayable therapy for treating infarcted myocardium; (iii) evaluate the therapeutic potential of the materials for treating infarcted murine hearts; and (iv) explore the biological response of this therapy in our animal model. We report the development, as well as the in vitro and in vivo testing, of a sprayable nano-therapeutic that uses surface engineered custom-designed multi-armed peptide grafted nanogold for on-the-spot coating of infarcted myocardial surface. When applied to mouse hearts, a 1-week after infarction, the spray-on treatment resulted in an increase in cardiac function (2.4-fold), muscle contractility, and myocardial electrical conductivity. The applied nanogold remained at the treatment site 28 days post-application with no off-target organ infiltration. Further, infarct size in the mice that received treatment was found to be < 10% of the total left ventricle area, while the number of blood vessels, pro-healing macrophages, and cardiomyocytes increased to levels comparable to that of a healthy animal.

Conclusion: We have demonstrated that by combining peptide design and an on-the-spot application, a therapeutic approach was developed that allows nanomolar concentrations of nanogold to restore cardiac function in a clinically relevant animal model of myocardial infarction. While the mechanism of action by which application of nanogold restores cardiac function post-myocardial infarction remains to be fully elucidated, including delivery of the therapy at different timepoints after heart injury. Our findings illustrate how peptide engineering can finely tune the properties of nanomaterials for use in therapeutic applications that in our case improved cardiac contractility and electrical signal propagation.