GGCX-金纳米粒子-透明质酸纳米复合物的构建及其对骨性关节炎治疗的探究

Osteoarthritis (OA) is the most pupular disease on orthopaedic in the elder, mainly manifested as the progressive destruction of articular cartilage. How to effectively delay the progress of OA and improve symptoms through using biotechnology and the latest drugs is a research hotspot. According to previous research has shown that gamma pancreatic acyl carboxylase (GGCX) associated with the degree of cartilage degeneration of OA, As results show that，the in vivo and in vitro of articular cartilage degeneration has certain inhibitory effect, can be used as a new drug for the treatment of OA. However, due to the problems of drug absorption and stability, it is hard to maintain effective drug concentration around joint. Gold nanoparticles can enter the cell through non-specific endocytosis, stabilize drug concentration and release of drugs taking in internal and external stimulation as the ideal drug carrier. Hyaluronic acid has little immune response combined with GGCX for targeted treatment of OA, and can be carried with gold nanoparticles to form an optical probe to dynamically monitor the therapeutic effect.In this study,the preparation of GGCX-AuNPs-HA nanocomposite was prepared and injected into the joint cavity of the osteoarthritis rabbit model,and assess the pharmacokinetics of it in vivo.

骨性关节炎（OA）是中老年最为常见的骨关节病，主要表现为关节软骨进行性破坏。如何通过生物技术与最新药物的运用有效延缓OA进展、改善症状是研究热点。据前期研究表明γ-谷氨酰基羧化酶(GGCX)与OA的软骨退变程度相关，体内外研究结果表明其对关节软骨的退变具有一定的抑制作用，可作为治疗OA的全新药物。但由于药物吸收性与稳定性等问题，很难维持关节内有效的药物浓度。金纳米粒子可通过非特异性内吞作用进入细胞，稳定药物浓度并根据内外部的刺激作用释放药物，是理想的药物载体。透明质酸免疫反应少，可配合GGCX对OA进行靶向治疗，并可通过与金纳米粒子结合，构成光学探针，动态监测治疗效果。本课题拟制备GGCX-AuNPs-HA纳米复合物，将其注射入骨性关节炎兔模型的关节腔内，研究其在体内的药物动力学。

研究结果表明γ-谷氨酰基羧化酶(GGCX)与OA的软骨退变程度相关,其对关节软骨的退变具有一定的抑制作用，可作为治疗OA的全新药物。金纳米粒子可通过非特异性内吞作用进入细胞，稳定药物浓度并根据内外部的刺激作用释放药物，是理想的药物载体。本课题制备了性能良好的金纳米复合物，我们发现金纳米复合物可以使OA软骨细胞 IL-1、TNF-α、MMP-13 的 mRNA 表达量降低以减轻炎症反应，并且可以使OA软骨细胞的凋亡率降低；体内实验表明，该金纳米复合物可以使SD大鼠的OA软骨胶原纤维比例、软骨面积增加，硬骨面积减少，对OA进展具有一定的抑制作用；我们还发现，该金纳米复合物可有效示踪炎性状态的细胞，具备定性示踪能力，并且该荧光探针与活性氧（ROS） 存在一定的正比例线性关系，可作为检测OA严重程度的检测试剂进而实现临床转化。