Department of Chemistry, POSTECH-CATHOLIC Biomedical Engineering Institute, POSTECH, Pohang 37673, South Korea.
OmniaMed Co., Ltd, Pohang 37666, Republic of Korea.
Biomater Sci. 2024 Mar 12;12(6):1477-1489. doi: 10.1039/d3bm01918g.
Osteoarthritis (OA) is a degenerative arthritis disease marked by inflammation, pain, and cartilage deterioration. Elevated nitric oxide (NO) levels play a pivotal role in mediating OA-related inflammation and are found in abundance within OA joints. This study introduces a NO-scavenging hyaluronic acid conjugate (HA-NSc) bearing both lubrication and anti-inflammatory properties for the treatment of osteoarthritis. For this, a derivative of -phenylenediamine (-PD) with good NO-scavenging capability (NSc) is designed, synthesized and chemically conjugated to HA. Owing to the amphiphilicity, this as-synthesized HA-NSc conjugate formed self-assembled nanoparticles (HA-NSc NPs) under aqueous conditions. When treated with activated murine macrophage RAW 264.7 cells that produce high levels of NO, these nanoparticles effectively reduced intracellular NO concentrations and inflammatory cytokines. In an OA animal model, the HA-NSc NPs significantly alleviated pain and diminished the cartilage damage due to the combined lubricating property of HA and NO-scavenging ability of NSc. Overall, the results from the study suggest HA-NSc NPs as a dual-action therapeutic agent for the treatment of OA by alleviating pain, inflammation, and joint damage, and also positioning the HA-NSc NPs as a promising candidate for innovative treatment of OA.
骨关节炎（OA）是一种退行性关节炎疾病，其特征为炎症、疼痛和软骨恶化。一氧化氮（NO）水平升高在介导 OA 相关炎症中起着关键作用，并且在 OA 关节中大量存在。本研究介绍了一种具有润滑和抗炎特性的 NO 清除透明质酸缀合物（HA-NSc），用于治疗骨关节炎。为此，设计、合成了一种具有良好 NO 清除能力（NSc）的 - 苯二胺（-PD）衍生物，并将其化学偶联到 HA 上。由于两亲性，这种合成的 HA-NSc 缀合物在水相条件下形成自组装纳米颗粒（HA-NSc NPs）。当用产生大量 NO 的活化的鼠巨噬细胞 RAW 264.7 细胞处理时，这些纳米颗粒有效地降低了细胞内的 NO 浓度和炎症细胞因子。在 OA 动物模型中，HA-NSc NPs 通过 HA 的润滑特性和 NSc 的 NO 清除能力显著缓解疼痛并减轻软骨损伤。总的来说，该研究结果表明，HA-NSc NPs 是一种通过缓解疼痛、炎症和关节损伤来治疗 OA 的双重作用治疗剂，并且将 HA-NSc NPs 作为一种有前途的 OA 创新治疗候选物。
