Stromal cell-derived factor-encapsulated nanoparticles target ischemic myocardium and attenuate myocardial injury via proangiogenic effects.

Abstract

Lipid bilayer nanoparticles (NPs) with and without stromal cell-derived factor (SDF) were created to target and treat ischemia/reperfusion (I/R)-injured myocardium. Male Wistar rats were subjected to myocardial I/R insult and, at reperfusion, randomized to receive systemic injections of 5 mL/kg PBS, 6 μg/kg of NPs, SDF, or SDF-NPs. Four days after treatment, SDF-NPs circulated and accumulated selectively in the ischemic myocardium, with an SDF concentration roughly three times that of the other three treatments. SDF-NP-treated rats had more endothelial progenitor cells (EPCs) in the blood and preserved capillaries and arterioles in the ischemic border myocardium four weeks post-treatment, which improved microvascular perfusion, reduced fibrosis, and preserved heart function. Notably, hearts treated with SDF-NPs retained left ventricular function at four weeks compared to 1-day post-treatment, with a 2.7 ± 1.2 % increase in the ejection fraction. The other three treatments decreased left ventricular function at four weeks (PBS: -7.8 ± 1.2 %, P < 0.001; empty NPs: -3.9 ± 1.3 %, P = 0.004; SDF solution: -5.1 ± 1.3 %, P = 0.001). Hence, systemically injected SDF-NPs selectively accumulate in ischemic cardiac tissue, shielding the myocardium from I/R injury via angiogenic effects through increased EPC migration. This novel cardioprotective drug may be clinically translatable.