Alginate sulfate-nanoparticles loaded with hepatocyte growth factor and insulin-like growth factor-1 improve left ventricular repair in a porcine model of myocardial ischemia reperfusion injury

• DOI: 10.1016/j.ejpb.2023.01.012
• Publication Date: 2023-01-21T16:14:34Z
• Authors: Ming Wu; Beatriz Pelacho; Piet Claus; Stijn De Buck; Denise Veltman; Hilde Gillijns; Patricia Holemans; Peter Pokreisz; Ellen Caluwé; Estefania Iglesia...; Smadar Cohen; Felipe Prosper; Stefan Janssens
• Keywords: 0301 basic medicine; 0303 health sciences; Hepatocyte Growth Factor; Sulfates; Swine; Myocardial Infarction; Myocardial Reperfusion Injury; 3. Good health; Disease Models, Animal; 03 medical and health sciences; Animals; Nanoparticles; Insulin-Like Growth Factor I

Nanomedicine offers great potential for the treatment of cardiovascular disease and particulate systems have the capacity to markedly improve bioavailability of therapeutics. The delivery of pro-angiogenic hepatocyte growth factor (HGF) and pro-survival and pro-myogenic insulin-like growth factor (IGF-1) encapsulated in Alginate-Sulfate nanoparticles (AlgS-NP) might improve left ventricular (LV) functional recovery after myocardial infarction (MI). In a porcine ischemia-reperfusion model, MI is induced by 75 min balloon occlusion of the mid-left anterior descending coronary artery followed by reperfusion. After 1 week, pigs (n = 12) with marked LV-dysfunction (LV ejection fraction, LVEF < 45%) are randomized to fusion imaging-guided intramyocardial injections of 8 mg AlgS-NP prepared with 200 µg HGF and IGF-1 (HGF/IGF1-NP) or PBS (Control). Intramyocardial injection is safe and pharmacokinetic studies of Cy5-labeled NP confirm superior cardiac retention compared to intracoronary infusion. Seven weeks after intramyocardial-injection of HGF/IGF1-NP, infarct size, measured using magnetic resonance imaging, is significantly smaller than in controls and is associated with increased coronary flow reserve. Importantly, HGF/IGF1-NP-treated pigs show significantly increased LVEF accompanied by improved myocardial remodeling. These findings demonstrate the feasibility and efficacy of using AlgS-NP as a delivery system for growth factors and offer the prospect of innovative treatment for refractory ischemic cardiomyopathy.