Synthesis of protein vesicles for extending time window of ischemic stroke treatment through microcirculatory thrombolysis
Synthesis of protein vesicles for extending time window of ischemic stroke treatment through microcirculatory thrombolysis
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DOI：
10.1016/j.cej.2022.140705
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发表时间：
2022-12
影响因子：
15.1
通讯作者：
Yingying Ren;Haiqiang Jin;Xiaotong Ma;Yuxuan Lu;Zhiyuan Shen;Jianwen Deng;Geoffrey I N Waterhouse;S. Guan;Yining Huang;X. Qu
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文献类型：
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作者：
Yingying Ren;Haiqiang Jin;Xiaotong Ma;Yuxuan Lu;Zhiyuan Shen;Jianwen Deng;Geoffrey I N Waterhouse;S. Guan;Yining Huang;X. Qu
微循环障碍是延长缺血性卒中治疗时间窗的主要障碍。本研究建立了一种动态模板法合成蛋白质囊泡的新方法，利用聚乙二醇（poly（ethylene glycol），poly（在小鼠大脑中动脉闭塞模型上，超静脉溶栓时间窗（> 4.5h）给予uPA@SOD囊泡可使脑侧支循环重新开放，有利于后期窗（>6 h）的大血管介入再通。这些导致缺氧条件的快速逆转和缺血组织中受损神经元的更有效的拯救。蛋白质囊泡的合成对中风治疗非常有益，同时能够轻松创建多蛋白质治疗系统。
Microcirculatory disturbances are a major barrier to extend the time window of ischemic stroke treatment. Herein, we developed a dynamic template method for the synthesis of protein vesicles, by which urokinase-type plasminogen activator (uPA) was crosslinked by poly(ethylene glycol)viapH sensitive host–guest interaction to form a protein gel-shell to encapsulate superoxide dismutase (SOD) for getting cascade biofunctions of microvessel thrombolysis and reperfusion injury inhibition. On a middle cerebral artery occlusion mouse model, the uPA@SOD vesicles administrated beyond intravenous thrombolysis time window (>4.5 h) could reopen the collateral circulation of brain, thus benefiting the followed interventional recanalization of large vessel in the late window (>6 h). These led to rapid reversion of hypoxia condition and more efficient rescue of injured neurons in the ischemic tissue. The synthesis of protein vesicles is highly beneficial for stroke treatment, meanwhile enabling the facile creation of multi-protein therapeutic systems.