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具有ROS清除、抗细胞焦亡和细胞外基质再生功能的微环境响应性金属-酚网络释放平台用于椎间盘退变

Microenvironment-responsive metal-phenolic network release platform with ROS scavenging, anti-pyroptosis, and ECM regeneration for intervertebral disc degeneration.

作者信息

Zhou Hao, He Jinpeng, Liu Renfeng, Cheng Jun, Yuan Yuhao, Mao Wanpu, Zhou Jun, He Honghui, Liu Qianqi, Tan Wei, Shuai Cijun, Deng Youwen

机构信息

Department of Spine Surgery, The Third Xiangya Hospital, Central South University, Changsha, Hunan, 410013, China.

Department of Joint Surgery and Sports Medicine, The Affiliated Nanhua Hospital, Hengyang Medical School, University of South China, Hengyang, Hunan, 421002, China.

出版信息

Bioact Mater. 2024 Mar 15;37:51-71. doi: 10.1016/j.bioactmat.2024.02.036. eCollection 2024 Jul.

DOI:10.1016/j.bioactmat.2024.02.036
PMID:38515609
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10954684/
Abstract

Intervertebral disc degeneration (IVDD) can be caused by aging, injury, and genetic factors. The pathological changes associated with IVDD include the excessive accumulation of reactive oxygen species (ROS), cellular pyroptosis, and extracellular matrix (ECM) degradation. There are currently no approved specific molecular therapies for IVDD. In this study, we developed a multifunctional and microenvironment-responsive metal-phenolic network release platform, termed TMP@Alg-PBA/PVA, which could treat (IL-1β)-induced IVDD. The metal-phenolic network (TA-Mn-PVP, TMP) released from this platform targeted mitochondria to efficiently scavenge ROS and reduce ECM degradation. Pyroptosis was suppressed through the inhibition of the IL-17/ERK signaling pathway. These findings demonstrate the versatility of the platform. And in a rat model of IVDD, TMP@Alg-PBA/PVA exhibited excellent therapeutic effects by reducing the progression of the disease. TMP@Alg-PBA/PVA, therefore, presents clinical potential for the treatment of IVDD.

摘要

椎间盘退变（IVDD）可由衰老、损伤和遗传因素引起。与IVDD相关的病理变化包括活性氧（ROS）过度积累、细胞焦亡和细胞外基质（ECM）降解。目前尚无批准用于IVDD的特异性分子疗法。在本研究中，我们开发了一种多功能且对微环境有响应的金属-酚网络释放平台，称为TMP@Alg-PBA/PVA，它可以治疗白细胞介素-1β（IL-1β）诱导的IVDD。该平台释放的金属-酚网络（TA-Mn-PVP，TMP）靶向线粒体以有效清除ROS并减少ECM降解。通过抑制IL-17/ERK信号通路抑制焦亡。这些发现证明了该平台的多功能性。在IVDD大鼠模型中，TMP@Alg-PBA/PVA通过减缓疾病进展表现出优异的治疗效果。因此，TMP@Alg-PBA/PVA在治疗IVDD方面具有临床潜力。

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