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

被引：72

作者：

Chen, Jiaxin ^{[1
]}

Zhu, Haifeng ^{[1
]}

Zhu, Yutao ^{[1
]}

Zhao, Chenchen ^{[1
]}

Wang, Shengyu ^{[1
]}

Zheng, Yixin ^{[1
]}

Xie, Ziang ^{[1
]}

Jin, Yang ^{[1
]}

Song, Honghai ^{[1
]}

Yang, Linjun ^{[1
]}

Zhang, Jin ^{[2
]}

Dai, Jiayong ^{[1
]}

Hu, Zhijun ^{[1
]}

Wang, Huaiyu ^{[3
]}

机构：

[1] Zhejiang Univ, Key Lab Musculoskeletal Syst Degenerat, Regenerat Translat Res Zhejiang Prov, Dept Orthopaed Surg,Sir Run Run Shaw Hosp,Sch Med, East Qing Chun Rd, Hangzhou 310016, Peoples R China

[2] Fuzhou Univ, Coll Chem Engn, 2 Xueyuan Rd, Fuzhou 350108, Peoples R China

[3] Chinese Acad Sci, Shenzhen Inst Adv Technol, Ctr Human Tissues & Organs Degenerat, Shenzhen 518055, Guangdong, Peoples R China

来源：

BIOACTIVE MATERIALS | 2022年 / 9卷

基金：

中国国家自然科学基金;

关键词：

STING; IVD degeneration; siRNA delivery; Injectable hydrogel; Dynamic Schiff base; CYTOSOLIC-DNA; ADAPTER; 2ND-MESSENGER; ACTIVATION;

D O I：

10.1016/j.bioactmat.2021.08.003

中图分类号：

R318 [生物医学工程];

学科分类号：

0831 ;

摘要：

Inflammatory responses of nucleus pulposus (NP) can induce imbalanced anabolism and catabolism of extracellular matrix, and the cytosolic dsDNA accumulation and STING-NE-kappa B 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.

引用

页码：29 / 43

页数：15

共 59 条

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