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

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.

Automated summary

In this study, rod-shaped polylactic acid polyglycolic acid nanoparticles encapsulated with piceatannol were developed to target and interfere with the interaction between neutrophils and inflamed endothelial cells in ischemic stroke. The nanoparticles with an aspect ratio of 5 exhibited enhanced internalization by neutrophils and were able to block neutrophil adherence to endothelial cells and inhibit infiltration into the blood-brain barrier. The released piceatannol within the ischemic region also inhibited neuroinflammation.