In vivo evaluation of urokinase-loaded hollow nanogels for sonothrombolysis on suture embolization-induced acute ischemic stroke rat model  

作　　者：Yuming Teng Haiqiang Jin Ding Nan Mengnan Li Chenghe Fan Yuanyuan Liu Pu Lv Wei Cui Yongan Sun Hongjun Hao Xiaozhong Qu Zhenzhong Yang Yining Huang 

机构地区：[1]Department of Neurology,Peking University First Hospital,Beijing 100034,China [2]State Key Laboratory of Polymer Physics and Chemistry,Institute of Chemistry,Chinese Academy of Sciences,Beijing 100190,China [3]College of Materials and Opto-Electronic Technology,University of Chinese Academy of Sciences,Beijing 100049,China

出　　处：《Bioactive Materials》2018年第1期102-109,共8页生物活性材料（英文）

基　　金：This work is financially supported by the National Natural Science Foundation of China(81400941,51473169).

摘　　要：The urokinase-type plasminogen activator(uPA)loaded hollow nanogels(nUK)were synthesized by a one-step reaction of glycol chitosan and aldehyde capped poly(ethylene oxide).The resultant formulation is sensitive to diagnostic ultrasound(US)of 2 MHz.Herein,we evaluated the in vivo sonothrombolysis performance of the nUK on acute ischemic stroke rat model which was established by suture embolization of middle cerebral artery(MCA).Via intravenous(i.v.)administration,the experimental data prove a controlled release of the therapeutic protein around the clots under ultrasound stimulation,leading to enhanced thrombolysis efficiency of the nUK,evidenced from smaller infarct volume and better clinical scores when compared to the i.v.dose of free uPA no matter with or without US intervention.Meanwhile,the preservation ability of the nanogels not only prolonged the circulation duration of the protein,but also resulted in the better blood-brain barrier protection of the nUK formulation,showing no increased risk on the hemorrhagic transformation than the controls.This work suggests that the nUK is a safe sonothrombolytic formulation for the treatment of acute ischemic stroke.

关 键 词：Hollow nanogel Ultrasound responsive Urokinase delivery THROMBOLYSIS In vivo evaluation 

分 类 号：R73[医药卫生—肿瘤]