Liu Sitong, Zhang Chen, Zhou Yuanyuan, Zhang Fang, Duan Xiaohui, Liu Yang, Zhao Xibang, Liu Jie, Shuai Xintao, Wang Jiali, Cao Zhong
School of Biomedical Engineering, Shenzhen Campus of Sun Yat-sen University, Shenzhen, Guangdong, 518107, China.
Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, 510120, China.
Biomaterials. 2023 Apr;295:122030. doi: 10.1016/j.biomaterials.2023.122030. Epub 2023 Jan 31.
Since the progression of osteoarthritis (OA) is closely associated with synovitis and cartilage destruction, the inhibition of inflammatory responses in synovial macrophages and reactive oxygen species (ROS) induced apoptosis in chondrocytes is crucial for OA amelioration. However, most of the current anti-inflammatory and antioxidant drugs are small molecules apt to be eliminated in vivo. Herein, mesoporous polydopamine nanoparticles (DAMM NPs) doped with arginine and manganese (Mn) ions were prepared to load dexamethasone (DEX) for OA intervention. A series of in vitro studies showed that the sustained release of DEX from DAMM NPs suppressed synovial inflammation and simultaneously inhibited toll-like receptor 3 (TLR-3) production in chondrocytes, contributing to prevention of chondrocyte apoptosis through the inflammatory factor-dependent TLR-3/NF-κB signaling pathway via modulation of macrophage-chondrocyte crosstalk. In addition, DAMM NPs exerted a predominant role in removal of ROS generated in chondrocytes. Therefore, the DEX-loaded DAMM NPs significantly attenuated OA development in mice model. Importantly, the T1-T2 magnetic contrast capabilities of DAMM NPs allowed an MRI-trackable delivery, manifesting a distinct feature widely regarded to boost the potential of nanomedicines for clinical applications. Together, our developed antioxidant-enhanced DAMM NPs with MRI-visible signals may serve as a novel multifunctional nanocarriers for prevention of OA progression.
由于骨关节炎（OA）的进展与滑膜炎和软骨破坏密切相关，抑制滑膜巨噬细胞中的炎症反应以及活性氧（ROS）诱导的软骨细胞凋亡对于改善OA至关重要。然而，目前大多数抗炎和抗氧化药物都是小分子，易于在体内被清除。在此，制备了掺杂精氨酸和锰（Mn）离子的介孔聚多巴胺纳米颗粒（DAMM NPs）以负载地塞米松（DEX）用于OA干预。一系列体外研究表明，DEX从DAMM NPs中的持续释放抑制了滑膜炎症，同时抑制了软骨细胞中Toll样受体3（TLR-3）的产生，通过调节巨噬细胞-软骨细胞间的相互作用，有助于通过炎症因子依赖性的TLR-3/NF-κB信号通路预防软骨细胞凋亡。此外，DAMM NPs在清除软骨细胞中产生的ROS方面发挥了主要作用。因此，负载DEX的DAMM NPs显著减轻了小鼠模型中OA的发展。重要的是，DAMM NPs的T1-T2磁对比能力允许进行MRI跟踪递送，展现出一种被广泛认为可提升纳米药物临床应用潜力的独特特征。总之，我们开发的具有MRI可见信号的抗氧化增强型DAMM NPs可作为预防OA进展的新型多功能纳米载体。
