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生物相容性氨基修饰钽纳米颗粒持续清除关节内活性氧并缓解骨关节炎

Sustained intra-articular reactive oxygen species scavenging and alleviation of osteoarthritis by biocompatible amino-modified tantalum nanoparticles.

作者信息

Jiang Yunsheng, Li Tao, Yang Junjun, Wang Xin, Song Xiongbo, Chen Guangxing, Dai Gang, Li Rong, Yao Chunyan, Chen Jiajia, Chen Cheng, Gong Xiaoyuan, Yang Liu

机构信息

Center for Joint Surgery, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China.

State Key Laboratory of Trauma, Burns and Combined Injury, Chongqing Engineering Research Center for Nanomedicine, Institute of Combined Injury, College of Preventive Medicine, Third Military Medical University (Army Medical University), Chongqing, China.

出版信息

Front Bioeng Biotechnol. 2023 Jan 13;11:1118850. doi: 10.3389/fbioe.2023.1118850. eCollection 2023.

Abstract

Recent studies highlight the vital role of oxidative stress and reactive oxygen species (ROS) during progression of osteoarthritis (OA). Attenuating oxidative stress and reducing reactive oxygen species generation in joints represent reasonable strategies for the treatment of osteoarthritis. To address the potential question for clinical translation, and improve the biocompatibility and long-term performance of current antioxidants, the present study provided high biocompatible small positively charged tantalum nanoparticles (Ta-NH NPs) with sustained intra-articular catalase activity and first applied to osteoarthritis intervention. Our results showed that Ta-NH NPs were stable with good biocompatibility, and protected viability and hyaline-like phenotype in HO-challenged chondrocytes. In addition, the biodistribution data demonstrated a sustained retention of Ta-NH NPs in the joint cavity, particularly in articular cartilage without organ toxicity and abnormality in hemogram or blood biochemistry indexes. Finally, compared with catalase (CAT), Ta-NH NPs exhibited long-term therapeutic effect in monosodium iodoacetate (MIA) induced osteoarthritis model. This study preliminarily explored the potential of simply modified metal nanoparticles as effective reactive oxygen species scavenging agent for osteoarthritis intervention, and offered a novel strategy to achieve sustained reactive oxygen species suppression using biocompatible Ta-based nano-medicine in oxidative stress related diseases.

摘要

近期研究突显了氧化应激和活性氧(ROS)在骨关节炎(OA)进展过程中的关键作用。减轻关节中的氧化应激并减少活性氧的产生是治疗骨关节炎的合理策略。为了解决临床转化的潜在问题,并提高当前抗氧化剂的生物相容性和长期性能,本研究提供了具有持续关节内过氧化氢酶活性的高生物相容性带正电的小钽纳米颗粒(Ta-NH NPs),并首次将其应用于骨关节炎干预。我们的结果表明,Ta-NH NPs稳定且具有良好的生物相容性,并且在HO刺激的软骨细胞中保护了细胞活力和透明样表型。此外,生物分布数据表明Ta-NH NPs在关节腔中持续保留,特别是在关节软骨中,且对器官无毒性,血常规或血液生化指标也无异常。最后,与过氧化氢酶(CAT)相比,Ta-NH NPs在碘乙酸钠(MIA)诱导的骨关节炎模型中表现出长期治疗效果。本研究初步探索了简单修饰的金属纳米颗粒作为有效的活性氧清除剂用于骨关节炎干预的潜力,并提供了一种新策略,即使用生物相容性钽基纳米药物在氧化应激相关疾病中实现持续的活性氧抑制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0ae7/9880278/ad6758e62bb9/fbioe-11-1118850-g001.jpg

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