NRLP-Val at 8 mg/kg significantly reduced infarct size, inhibited fibrosis, and restored cardiac function at 28 days post-myocardial ischemia/reperfusion injury compared to free valsartan.
Does NRLP-Val reduce infarct size and improve cardiac remodeling in a murine model of myocardial ischemia/reperfusion injury?
A neutrophil-mimetic, ROS-responsive nanocarrier delivering valsartan effectively targets the ischemic myocardium to reduce reperfusion injury and improve cardiac remodeling in mice.
Myocardial ischaemia/reperfusion (MI/R) injury causes adverse cardiac remodelling by activating the local renin-angiotensin system (RAS). In this study, we engineered a neutrophil membrane-biomimetic nanocarrier that facilitates the reactive oxygen species (ROS)-responsive release of valsartan (NRLP-Val) to precisely target MI/R injury. This design leverages neutrophil-derived adhesion molecules for targeted delivery to the inflamed myocardium and promotes ROS-triggered drug release at the infarct site. NRLP-Val effectively traversed activated endothelium and protected cardiomyocytes from angiotensin II-induced mitochondrial dysfunction and apoptosis in vitro. In vivo, NRLP-Val demonstrated superior cardiac accumulation and a dose-dependent therapeutic profile in a murine MI/R model. Notably, the 8 mg/kg dose achieved maximal efficacy, which was statistically equivalent to that of the 12 mg/kg dose, in acutely reducing the infarct size, oxidative stress, apoptosis, and inflammation. Long-term treatment with 8 mg/kg NRLP-Val significantly inhibited fibrosis, improved ventricular remodelling, and restored cardiac function at 28 days, outperforming the non-targeted controls and free valsartan. The platform exhibited an excellent safety profile. Therefore, 8 mg/kg NRLP-Val is a promising and clinically translatable strategy for achieving potent local RAS inhibition without systemic compromise, offering a novel targeted therapeutic approach for ischaemic heart disease.
Yakufu et al. (Wed,) conducted a other in Myocardial ischemia/reperfusion injury. NRLP-Val vs. PBS, free Valsartan, RLP-Val was evaluated on Cardiac function (LVEF, LVFS) and ventricular remodeling at 28 days. NRLP-Val at 8 mg/kg significantly reduced infarct size, inhibited fibrosis, and restored cardiac function at 28 days post-myocardial ischemia/reperfusion injury compared to free valsartan.