Inflammation-responsive monocyte-biomimetic nanobubbles realizing microvascular recanalization and xenon neuroprotection in ischemic stroke

Abstract

Ischemic stroke (IS) is an acute and severed disease with vascular inflammation prior to thrombus events. Considering the current treatment strategies focus on the thrombus-target effect, reaching the early intervention and extending therapeutic time windows remains a key challenge. Herein, inspired by the monocyte infiltration mechanism to the early stroke lesion, nanobubbles encapsulating xenon with monocyte membrane shell (Xe-MNBs) are designed for emergency theranostics of IS. Xe-MNBs quickly target to the inflammatory damaged vessels and competitively inhibit the inflammatory progression via abundant membrane cytokine receptors. Afterwards, Xe-MNBs serve as a platform to recanalize microvasculature and locally deliver neuroprotective Xe in the stroke lesion, synergistically extending the “door-to-needle” streamline. In photothrombotic ischemic stroke mice, the aggregation of Xe-MNBs in stroke brains reaches approximately 8.2 times higher than normal brains within 0.5 h of stroke induction. In vivo results confirmed that blood flow perfusion, neuroprotection and inflammation inhibition can significantly improve the neurological recovery of stroke mice, also investigated by gene transcriptome analysis. This work provides a novel monocyte-biomimetic nanosystem for inflammation-responsive drug delivery and gives a proof of concept for priority management of IS with Xe-MNBs.