1. Academic Validation
  2. Molecularly imprinted nanoparticles hitchhiking on neutrophils for precise treatment of ischemic stroke

Molecularly imprinted nanoparticles hitchhiking on neutrophils for precise treatment of ischemic stroke

  • J Colloid Interface Sci. 2025 Jul:689:137246. doi: 10.1016/j.jcis.2025.03.035.
Ruizhen Lv 1 Fang Li 2 Yong Liu 3 Mingzhu Song 4 Jiayu Yuan 5 Ge Zhang 6 Mengdi Sun 7 Yifei Zhang 8 Xiangchen Su 9 Yuting Zhao 10 Jia Dong 11 Yijie Shi 12 Liang Zhao 13
Affiliations

Affiliations

  • 1 School of Pharmacy, Jinzhou Medical University, Jinzhou 121000, China. Electronic address: lvruizhen0902@163.com.
  • 2 School of Pharmacy, Jinzhou Medical University, Jinzhou 121000, China. Electronic address: jyyxlifang@163.com.
  • 3 School of Pharmacy, Jinzhou Medical University, Jinzhou 121000, China. Electronic address: ly13697799544@163.com.
  • 4 School of Pharmacy, Jinzhou Medical University, Jinzhou 121000, China. Electronic address: songsong191326@163.com.
  • 5 School of Pharmacy, Jinzhou Medical University, Jinzhou 121000, China. Electronic address: yuanjiayukm@163.com.
  • 6 School of Pharmacy, Jinzhou Medical University, Jinzhou 121000, China. Electronic address: zhangge0625@163.com.
  • 7 School of Pharmacy, Jinzhou Medical University, Jinzhou 121000, China. Electronic address: sunmengdi5@163.com.
  • 8 School of Pharmacy, Jinzhou Medical University, Jinzhou 121000, China. Electronic address: zyf1234567890422@163.com.
  • 9 School of Pharmacy, Jinzhou Medical University, Jinzhou 121000, China. Electronic address: 1368386534@qq.com.
  • 10 School of Pharmacy, Jinzhou Medical University, Jinzhou 121000, China. Electronic address: zhaoyutingcd@163.com.
  • 11 School of Pharmacy, Jinzhou Medical University, Jinzhou 121000, China. Electronic address: dj1180@163.com.
  • 12 School of Pharmacy, Jinzhou Medical University, Jinzhou 121000, China; Collaborative Innovation Center for Age-related Disease, Jinzhou Medical University, Jinzhou, Liaoning, China. Electronic address: shiyijie119@163.com.
  • 13 School of Pharmacy, Jinzhou Medical University, Jinzhou 121000, China; Collaborative Innovation Center for Age-related Disease, Jinzhou Medical University, Jinzhou, Liaoning, China; Key Laboratory of Neurodegenerative Diseases of Liaoning Province, Jinzhou Medical University, Jinzhou, China. Electronic address: liangzhao79@163.com.
Abstract

Ischemic stroke (IS), the most prevalent type of stroke worldwide, is associated with a variety of complex processes, including oxidative stress, Apoptosis, and Ferroptosis. Recent findings indicate that inhibiting iron overload as a key regulatory mechanism of Ferroptosis profoundly influences the pathogenesis and treatment of IS. In addition, enhanced blood-brain barrier (BBB) penetration and precise targeting of the ischaemic site contribute to improved therapeutic outcomes in IS. In this study, we developed FeSO4 templated-molecularly imprinted nanoparticles (MINPs) with high-affinity recognition of ferrous ions (Fe2+). MINPs exhibited physicochemical properties that perfectly match the polarity and condensed structure of Fe2+, resulting in the effective and specific clearance of Fe2+ through efficient and selective adsorption both in vivo and in vitro. Moreover, MINPs hitchhiked circulating neutrophils, thereby facilitating their penetration through BBB and enhancing targeted delivery to the ischemic brain. Our results, supported by transcriptomic analysis, further elucidated the molecular mechanisms by which MINPs significantly inhibit Ferroptosis while concurrently regulating Apoptosis and inflammation, thereby conferring marked neuroprotection against IS.

Keywords

Ferroptosis; Ferrous ions; Ischemic stroke; Molecularly imprinted nanoparticles; Neutrophil.

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