Injectable self-healing hydrogel with siRNA delivery property for sustained STING silencing and enhanced therapy of intervertebral disc degeneration

查看全文 作　　者：Jiaxin [1]Chen;Haifeng [1]Zhu;Yutao [1]Zhu;Chenchen [1]Zhao;Shengyu [1]Wang;Yixin [1]Zheng;Ziang [1]Xie;Yang [1]Jin;Honghai [1]Song;Linjun [1]Yang;Jin [2]Zhang;Jiayong [1]Dai;Zhijun [1]Hu;Huaiyu [3]Wang

机构地区：[1]Department of Orthopaedic Surgery,Sir Run Run Shaw Hospital,Zhejiang University School of Medicine,Key Laboratory of Musculoskeletal System Degeneration,Regeneration Translational Research of Zhejiang Province,East Qing Chun Road,Hangzhou,310016,PR China;[2]College of Chemical Engineering,Fuzhou University,2 Xueyuan Road,Fuzhou,350108,PR China;[3]Center for Human Tissues and Organs Degeneration,Shenzhen Institutes of Advanced Technology,Chinese Academy of Sciences,Shenzhen,518055,Guangdong,PR China

出　　处：《Bioactive Materials》索引2022年第7卷第3期,共15页

基　　金：The study was sponsored by National Natural Science Foundation of China(81672150,51903050);Zhejiang medical and health science and technology project(2018KY117,2019ZD041);Natural Science Foundation of Zhejiang Province of China(LQ20H160053);New talent in medical field of Zhejiang Province,and the fundamental research funds for the central universities(2019QNA7027). 摘　　要：Inflammatory responses of nucleus pulposus(NP)can induce imbalanced anabolism and catabolism of extracellular matrix,and the cytosolic dsDNA accumulation and STING-NF-κB pathway activation found in NP inflammation are considered as fairly important cause of intervertebral disc(IVD)degeneration.Herein,we constructed a siSTING delivery hydrogel of aldehyde hyaluronic acid(HA-CHO)and poly(amidoamine)PAMAM/siRNA complex to intervene the abnormal STING signal for IVD degeneration treatment,where the formation of dynamic Schiff base bonds in the system(siSTING@HPgel)was able to overcome the shortcomings such as low cellular uptake,short half-life,and rapid degradation of siRNA-based strategy.PAMAM not only formed complexes with siRNA to promote siRNA transfection,but also served as dynamic crosslinker to construct hydrogel,and the injectable and self-healing hydrogel efficiently and steadily silenced STING expression in NP cells.Finally,the siSTING@HPgel significantly eased IVD inflammation and slowed IVD degeneration by prolonging STING knockdown in puncture-induced IVD degeneration rat model,revealing that STING pathway was a therapeutic target for IVD degeneration and such novel hydrogel had great potential for being applied to many other diseases for gene delivery. 关键词：STING IVD degeneration siRNA delivery Injectable hydrogel Dynamic Schiff base

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Injectable self-healing hydrogel with siRNA delivery property for sustained STING silencing and enhanced therapy of intervertebral disc degeneration

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