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Microthrombus‐Targeting Micelles for Neurovascular Remodeling and Enhanced Microcirculatory Perfusion in Acute Ischemic Stroke
Author(s) -
Lu Yifei,
Li Chao,
Chen Qinjun,
Liu Peixin,
Guo Qin,
Zhang Yu,
Chen Xinli,
Zhang Yujie,
Zhou Wenxi,
Liang Donghui,
Zhang Yiwen,
Sun Tao,
Lu Weigen,
Jiang Chen
Publication year - 2019
Publication title -
advanced materials
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 10.707
H-Index - 527
eISSN - 1521-4095
pISSN - 0935-9648
DOI - 10.1002/adma.201808361
Subject(s) - neurovascular bundle , neuroprotection , micelle , ischemia , neuroinflammation , microglia , materials science , neuroscience , stroke (engine) , medicine , inflammation , pharmacology , cardiology , chemistry , biology , pathology , mechanical engineering , aqueous solution , engineering
Abstract Reperfusion injury exists as the major obstacle to full recovery of neuron functions after ischemic stroke onset and clinical thrombolytic therapies. Complex cellular cascades including oxidative stress, neuroinflammation, and brain vascular impairment occur within neurovascular units, leading to microthrombus formation and ultimate neuron death. In this work, a multitarget micelle system is developed to simultaneously modulate various cell types involved in these events. Briefly, rapamycin is encapsulated in self‐assembled micelles that are consisted of reactive oxygen species (ROS)‐responsive and fibrin‐binding polymers to achieve micelle retention and controlled drug release within the ischemic lesion. Neuron survival is reinforced by the combination of micelle facilitated ROS elimination and antistress signaling pathway interference under ischemia conditions. In vivo results demonstrate an overall remodeling of neurovascular unit through micelle polarized M2 microglia repair and blood–brain barrier preservation, leading to enhanced neuroprotection and blood perfusion. This strategy gives a proof of concept that neurovascular units can serve as an integrated target for ischemic stroke treatment with nanomedicines.