Microthrombus‐Targeting Micelles for Neurovascular Remodeling and Enhanced Microcirculatory Perfusion in Acute Ischemic Stroke. Issue 21 (8th April 2019)

• Record Type: Journal Article
• Authors: 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
• Is Part Of: Advanced materials. Volume 31:Issue 21(2019)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2019-04-08
• Subjects: ischemic stroke -- microenvironment modulation -- microglia polarization -- neurovascular units -- no‐reflow; Materials -- Periodicals; Chemical vapor deposition -- Periodicals; 620.11
• DOI: 10.1002/adma.201808361
• Languages: English
• ISSNs: 0935-9648

Abstract

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. Abstract : A microthrombus‐targeting and neurovascular‐remodeling micelle system is developed, exhibiting multitarget modulations including microglia polarization, autophagy enhancement, and blood–brain barrier repairment against ischemic stress and reperfusion injury. Through the positive intervention of cellular crosstalk within neurovascular units in the ischemic penumbra, enhanced neuroprotection and improved cerebral blood perfusion are achieved for better neurological outcomes.