Rod‐Shaped Polymeric Nanoparticles Intervene Neutrophils for Efficient Ischemic Stroke Therapy

• Published in: Advanced functional materials 2023-05, Vol.33 (19), p.n/a
• Main Authors: Song, Zhuolun, Fang, Jinghuan, Wang, Zhenhua, Xiao, Renming, Guo, Xing, Zhou, Shaobing
• Format: Article
• Language: English
• Subjects: Aspect ratio; Brain; drug delivery; Endothelial cells; Macrophages; Materials science; nanocarriers; Nanoparticles; neuroinflammation alleviation; neutrophil intervention; Neutrophils; Occlusion; Polyglycolic acid; Polylactic acid; Stroke; stroke therapy; Therapy
• ISSN: 1616-301X; 1616-3028
• DOI: 10.1002/adfm.202212326

Neutrophils are associated with pro‐inflammation and contribute to pathophysiology of ischemic stroke. Prevention of neutrophils from infiltrating into ischemic area can be a potential approach for stroke therapy. In this study, a rod‐shaped polylactic acid polyglycolic acid (PLGA) nanoparticles encapsulated with piceatannol is developed to target and intervene the interaction of neutrophils with inflamed endothelial cells. In contrast to macrophages, neutrophils exhibit enhanced endocytosis of elongated particles. The nanoparticles with aspect ratio (AR) of 5 display higher internalization by neutrophils compared to other nanoparticles. Thus, AR5 nanoparticles are screened out to load with piceatannol (Pic@AR5) for investigating the therapeutic effect against middle cerebral artery occlusion model. It is demonstrated that Pic@AR5 can block the adherence of neutrophils to endothelial cells, inhibiting the infiltration of neutrophils into blood‐brain barrier (BBB). Besides, the inflammatory cytokine of ischemic brain can also be reduced even if a small part of Pic@AR5‐carried neutrophils enter BBB. The nanoparticles release piceatannol within the ischemic region, which inhibit microglial Syk signal and result in alleviation of neuroinflammation. This strategy provides new insights into ischemic stroke therapy. A rod‐shaped PLGA nanoplatform loading with piceatannol is successfully developed for preventing the infiltration of neutrophils into blood‐brain barrier (BBB) and alleviating neuroinflammation in microglia by inhibiting the Syk signaling. With this nanoplatform, an effective therapeutic efficiency is achieved in acute ischemic stroke through obvious reduction of infarct volume, significant behavioral recovery, and remarkable BBB protective effect.