@article{Yakufu2026, 
author = {Wusiman Yakufu and Yuekai Shi and Jinfeng Gao and Ayitongguli Aimaiti and Nueraili Kadi and Qiyu Li and Miribanguli Alifu and Aikebaier Yasen and Muhetaer Wubuli and Yang Pang and Su Li and Zhenzhen Huang and Rongrong Lu and Maimaitiaili Tuerxun and Reyimai Mutailipu and Abulimiti Jamali and Wumaierjiang Kelimu and Xianglin Tang and Qibing Wang and Yuqiong Chen and Abudureheman Mijiti and Zheyong Huang and Junbo Ge},
title = {Decoupling local renin-angiotensin system inhibition from systemic effects: A neutrophil-mimetic, ROS-responsive nanocarrier for precision therapy of myocardial ischemia/reperfusion injury},
year = {2026},
journal = {Nano Research},
volume = {19},
number = {8},
pages = {94908732},
keywords = {myocardial ischaemia/reperfusion injury, targeted drug delivery, neutrophil-mimetic nanocarrier, reactive oxygen species (ROS)-responsive, local renin-angiotensin system inhibition},
url = {https://www.sciopen.com/article/10.26599/NR.2026.94908732},
doi = {10.26599/NR.2026.94908732},
abstract = {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.}
}