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A natural polyphenolic nanoparticle--knotted hydrogel scavenger for osteoarthritis therapy

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机构: [1]Department of Oral & Cranio-Maxillofacial Surgery, Shanghai Ninth People’s Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology & Shanghai Research Institute of Stomatology, Shanghai, 200011, China [2]Department of Radiology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, 200072, China [3]College of Polymer Science and Engineering, State Key Laboratory of Polymer Materials Engineering, Sichuan University, Chengdu, 610065, China [4]Department of Thyroid Oncology, Chongqing University Cancer Hospital, Chongqing, 400030, China [5]Shanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedic Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, China [6]Department of Spine Surgery, Zhongda Hospital, Southeast University, Nanjing, 210009, China [7]School of Life Science, Shanghai Key Laboratory of Regulatory Biology, East China Normal University, Shanghai, 200241, China
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关键词: Osteoarthritis therapy Tea polyphenol nanoparticle Antioxidant Nitric oxide scavenging pH-responsive release

摘要:
Exploring highly efficient and cost-effective biomaterials for osteoarthritis (OA) treatment remains challenging, as current therapeutic strategies are difficult to eradicate the excessive reactive oxygen species (ROS) and nitric oxide (NO) at damaged sites. Tea polyphenol (TP) nanoparticles (NPs), a nature-inspired antioxidant in combination with 2-(4-Carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (carboxy-PTIO), a NO scavenger, could provide maximized positive therapeutic effects on OA by eradicating both ROS and NO. Notably, this combination not only improves the half-life of the TP monomer and the drug loading efficiency of carboxy-PTIO but also prevents nitrite from being harmful to tissue. Moreover, the protonation ability of carboxy-PTIO allows smart acid-responsive release in response to environmental pH, which provides conditioned treatment strategies for OA. In in vitro experiments, TP/PTIO NPs downregulated proinflammatory cytokine release via synergistic removal of ROS and NO and suppression of ROS/NF-κB and iNOS/NO/Caspase-3 signaling. For in vivo experiments, NPs were cross-linked with 4-arm-PEG-SH to form an injectable hydrogel system. The release of TP and carboxy-PTIO from the system efficiently prevents cartilage inflammation and damage via similar signaling pathways. Overall, the proposed system provides an efficient approach for OA therapy.© 2024 The Authors.

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出版当年[2025]版:
大类 | 1 区 医学
小类 | 1 区 工程:生物医学 1 区 材料科学:生物材料
最新[2025]版:
大类 | 1 区 医学
小类 | 1 区 工程:生物医学 1 区 材料科学:生物材料
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第一作者机构: [1]Department of Oral & Cranio-Maxillofacial Surgery, Shanghai Ninth People’s Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology & Shanghai Research Institute of Stomatology, Shanghai, 200011, China
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