NO-releasing double-crosslinked responsive hydrogels accelerate the treatment and repair of ischemic stroke  

作　　者：Wen Guo Cheng Hu Yue Wang Wen Zhang Shaomin Zhang Jin Peng Yunbing Wang Jinhui Wu 

机构地区：[1]Center of Gerontology and Geriatrics,National Clinical Research Center for Geriatrics,West China Hospital,Sichuan University,Chengdu 610041,China [2]National Engineering Research Center for Biomaterials,College of Biomedical Engineering,Med-X Center for Materials,Sichuan University,Chengdu 610064,China

出　　处：《Acta Pharmaceutica Sinica B》2025年第2期1112-1125,共14页药学学报(英文版)

基　　金：supported by the funding listed as follows:National Key R&D Program of China(Nos.2018YFC2002100 and 2018YFC2002103);Science and Technology Department of Sichuan Province(Grant No.24ZYZYTS0172 and 2025ZNSFSC1021,China);the Key R&D Support Program of Chengdu(No.2022YF0900001SN,China),National Natural Science Foundation of China(No.32301115);National Key Research and Development Programs(2023YFC2412802,China);Fundamental Research Funds for the Central Universities(2023SCUH0011 and YJ2021115,China).

摘　　要：Stroke is a global disease that seriously threatens human life.The pathological mechanisms of ischemic stroke include neuroinflammation,oxidative stress,and the destruction of blood vessels at the lesion site.Here,a biocompatible in situ hydrogel platform was designed to target multiple pathogenic mechanisms post-stroke,including anti-inflammation,anti-oxidant,and promotion of angiogenesis.Double-crosslinked responsive multifunctional hydrogels could quickly respond to the pathological microenvironment of the ischemic damage site and mediate the delivery of nitric oxide(NO)and ISO-1(inhibitor of macrophage migration inhibitory factor,MIF).The hydrogel demonstrated good biocompatibility and could scavenge reactive oxygen species(ROS)and inflammatory cytokines,such as interleukin-6(IL-6),interleukin-10(IL-10),and MIF.In a mouse stroke model,hydrogels,when situated within the microenvironment of cerebral infarction characterized by weak acidity and elevated ROS release,would release anti-inflammatory nanoparticles rapidly that exert an anti-inflammatory effect.Concurrently,NO was sustained release to facilitate angiogenesis and provide neuroprotective effects.Neurological function was significantly improved in treated mice as assessed by the modified neurological severity score,rotarod test,and open field test.These findings indicate that the designed hydrogel held promise for sustained delivery of NO and ISO-1 to alleviate cerebral ischemic injury by responding to the brain's pathological microenvironment.

关 键 词：Hydrogel Nitric oxide Ischemic stroke Angiogenesis Anti-inflammation Macrophage migration inhibitory factor NEUROPROTECTIVE Double-crosslinked 

分 类 号：R743.3[医药卫生—神经病学与精神病学]