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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\u2010assembled micelles that are consisted of reactive oxygen species (ROS)\u2010responsive and fibrin\u2010binding 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\u2013brain 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.<\/jats:p>","DOI":"10.1002\/adma.201808361","type":"journal-article","created":{"date-parts":[[2019,4,8]],"date-time":"2019-04-08T05:31:12Z","timestamp":1554701472000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":179,"title":["Microthrombus\u2010Targeting Micelles for Neurovascular Remodeling and Enhanced Microcirculatory Perfusion in Acute Ischemic Stroke"],"prefix":"10.1002","volume":"31","author":[{"given":"Yifei","family":"Lu","sequence":"first","affiliation":[{"name":"Key Laboratory of Smart Drug Delivery Ministry of Education State Key Laboratory of Medical Neurobiology Department of Pharmaceutics School of Pharmacy Fudan University  Shanghai 201203 China"},{"name":"National Pharmaceutical Engineering and Research Center China State Institute of Pharmaceutical Industry  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