靶向线粒体的近红外响应型 MnO@PDA@Pd-SS31 纳米酶通过减轻氧化应激和逆转线粒体功能障碍缓解骨关节炎。

Mitochondrial-targeting and NIR-responsive MnO@PDA@Pd-SS31 nanozymes reduce oxidative stress and reverse mitochondrial dysfunction to alleviate osteoarthritis.

机构信息

Guangxi Engineering Center in Biomedical Materials for Tissue and Organ Regeneration, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, China; Collaborative Innovation Centre of Regenerative Medicine and Medical Bioresource Development and Application, Guangxi Key Laboratory of Regenerative Medicine，The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, China; Department of Orthopaedics Trauma and Hand Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, China; Department of Orthopedics, The Second Affiliated Hospital of Guangxi Medical University, Nanning, 530005, China.

出版信息

Biomaterials. 2024 Mar;305:122449. doi: 10.1016/j.biomaterials.2023.122449. Epub 2023 Dec 22.

DOI:10.1016/j.biomaterials.2023.122449

PMID:38194734

Abstract

Mitochondrial reactive oxygen species (mROS) play a crucial role in the process of osteoarthritis (OA), which may be a promising target for therapy of OA. In this study, novel mitochondrial-targeting and SOD-mimic MnO@PDA@Pd-SS31 nanozymes with near-infrared (NIR) responsiveness and synergistic cascade to scavenge mROS were designed for the therapy of OA. Results showed that the nanozymes accelerated the release of Pd and MnO under NIR irradiation, exhibiting enhanced activities of SOD and CAT mimic enzymes with reversed mitochondrial dysfunction and promoted mitophagy to effectively scavenge mROS from chondrocytes, modulate the microenvironment of oxidative stress, and eventually inhibit the inflammatory response. Nanozymes were excreted in vivo through intestinal metabolic pathway and had good biocompatibility, effectively reducing the inflammatory response and relieving articular cartilage degeneration in OA joints, with a reduction of 93.7 % and 93.8 % in OARSCI scores for 4 and 8 weeks respectively. Thus, this study demonstrated that the mitochondria targeting and NIR responsive MnO@PDA@Pd-SS31 nanozymes could efficiently scavenge mROS, repair damaged mitochondrial function and promote cartilage regeneration, which are promising for the treatment of OA in clinical applications.

摘要

线粒体活性氧（mROS）在骨关节炎（OA）的发生发展过程中发挥着关键作用，可能成为 OA 治疗的一个有前景的靶点。在本研究中，设计了一种新型的线粒体靶向、近红外（NIR）响应的 SOD 模拟 MnO@PDA@Pd-SS31 纳米酶，通过级联反应来清除 mROS，用于 OA 的治疗。结果表明，纳米酶在 NIR 照射下加速了 Pd 和 MnO 的释放，表现出增强的 SOD 和 CAT 模拟酶的活性，逆转了线粒体功能障碍，并促进了自噬以有效地从软骨细胞中清除 mROS，调节氧化应激的微环境，最终抑制炎症反应。纳米酶通过肠道代谢途径在体内排出，具有良好的生物相容性，有效减轻 OA 关节的炎症反应和缓解软骨退化，OARSCI 评分分别降低了 93.7%和 93.8%，4 周和 8 周时分别为 4 和 8 周。因此，本研究表明，线粒体靶向和 NIR 响应的 MnO@PDA@Pd-SS31 纳米酶可以有效地清除 mROS，修复受损的线粒体功能，促进软骨再生，有望在临床应用中用于治疗 OA。