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

作者：Qinfeng Ding, Yitong Wang, Tianyou Wang, Chengyao Zhang, Shengbing Yang, Lu Mao, Yiyun Cheng, Yiwen Li, Kaili Lin · 发表于：Bioactive Materials · 年份：2024 · DOI：10.1016/j.bioactmat.2024.09.037 · 被引用次数：22 · 研究领域：Osteoarthritis Treatment and Mechanisms、Proteoglycans and glycosaminoglycans research、Silk-based biomaterials and applications

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. Acid-responsive tea polyphenol nanoparticle-based hydrogel platform for osteoarthritis therapy through ...