Sheng Chuanyi, Zhu Baorong, Lin Xiaomei, Shen Hongyuan, Wu Zhonghua, Shi Jinjun, Ge Liang
Department of Clinical Laboratory, Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine, Nanjing, China.
Nanjing Liuhe District Hospital of Traditional Chinese Medicine, Nanjing, China.
J Drug Target. 2025 Jun;33(5):804-816. doi: 10.1080/1061186X.2024.2449488. Epub 2025 Jan 7.
In this study, we developed an intra-articular injectable hydrogel drug depot (SMN-CeO@G) for sustained OA treatment. This hydrogel system, which carries sinomenine-loaded cerium dioxide nanoparticles (SMN-CeO), enhances anti-inflammatory and anti-apoptotic effects within the joint cavity. SMN-CeO@G features a three-dimensional network structure with an approximate pore size of 10 μm, stably encapsulating SMN-CeO nanoparticles (∼75 nm). Under hydrogen peroxide (HO) exposure and simulated mechanical stress, SMN-CeO@G achieves a cumulative SMN release of 44.72 ± 7.83% over 48 hours, demonstrating controlled release capabilities. At an SMN concentration of 0.5 μg/mL, SMN-CeO@G significantly enhances proliferation, reduces apoptosis, and lowers matrix metalloproteinases-13 (MMP-13) secretion in IL-1β-induced ATDC5 chondrocytes. In the ATDC5-RAW264.7 co-culture model, SMN-CeO@G effectively reduces reactive oxygen species (ROS) levels, apoptosis (∼20%), and MMP13 concentrations (24.3 ± 3.1 ng/mL) in chondrocytes, likely due to the promotion of macrophages M2 polarisation. In anti-OA efficacy studies, a single intra-articular injection of SMN-CeO@G significantly reduces osteophyte formation, promotes subchondral bone normalisation, alleviates pain sensitivity, and lowers serum IL-1β (59.3 ± 2.4 pg/mL) and MMP-13 (23.6 ± 1.7 ng/mL) levels in OA model rats. SMN-CeO@G also achieves prolonged retention in the synovial fluid, with 6.7 ± 2.8% SMN still detectable at 72 hours post-injection, a factor crucial for sustained therapeutic effect. Overall, SMN-CeO@G presents a promising tool for intra-articular OA treatment.
在本研究中，我们开发了一种用于骨关节炎（OA）持续治疗的关节腔内可注射水凝胶药物储库（SMN-CeO@G）。这种携带负载青藤碱的二氧化铈纳米颗粒（SMN-CeO）的水凝胶系统增强了关节腔内的抗炎和抗凋亡作用。SMN-CeO@G具有三维网络结构，近似孔径为10μm，能稳定包裹SMN-CeO纳米颗粒（约75nm）。在过氧化氢（HO）暴露和模拟机械应力下，SMN-CeO@G在48小时内实现了44.72±7.83%的青藤碱累积释放，显示出控释能力。在青藤碱浓度为0.5μg/mL时，SMN-CeO@G显著增强白细胞介素-1β诱导的ATDC5软骨细胞的增殖、减少凋亡并降低基质金属蛋白酶-13（MMP-13）的分泌。在ATDC5-RAW264.7共培养模型中，SMN-CeO@G有效降低软骨细胞中的活性氧（ROS）水平、凋亡（约20%）和MMP13浓度（24.3±3.1ng/mL），这可能是由于促进了巨噬细胞M2极化。在抗OA疗效研究中，单次关节腔内注射SMN-CeO@G可显著减少骨赘形成，促进软骨下骨正常化，减轻疼痛敏感性，并降低OA模型大鼠血清白细胞介素-1β（59.3±2.4pg/mL）和MMP-13（23.6±1.7ng/mL）水平。SMN-CeO@G在滑液中的保留时间也延长，注射后72小时仍可检测到6.7±2.8%的青藤碱，这是实现持续治疗效果的关键因素。总体而言，SMN-CeO@G是一种用于关节腔内OA治疗的有前景的工具。
