脊髓损伤(SCI)是中枢神经系统严重的损伤，减少神经炎症、促轴突生长、保护神经元、康复训练等是治疗SCI的重要手段。我们前期研究显示，小分子药物氯喹(CQ)显著抑制早期神经炎症；大分子药物成纤维细胞生长因子10(FGF10)有效减少神经元凋亡、促进轴突生长，均有利于SCI后神经修复。若CQ和FGF10共同递送，协同康复训练可同时发挥多重作用治疗SCI。由于理化性质差异，两种不同性质药物联合靶向递送是难题，本项目拟构建可注射型脂质体丝素蛋白水凝胶，并以靶向硫酸软骨素蛋白聚糖(CSPG)的CAQK四肽修饰联合药物载体，以实现靶向到胶质瘢痕部位共载递送，结合减重平台训练，全面综合评价其协同治疗SCI作用，并结合多种分子生物学手段及组学技术探讨其协同机理。本项目利用靶向制剂新技术实现对两种不同性质的药物共同递送，结合康复训练发挥多重功效联合治疗SCI，将为SCI神经修复提供新的治疗策略。

Spinal cord injury (SCI) often causes permanent, devastating disabilities. Enhancing neuronal survival, inhibiting inflammation, promoting plasticity and axonal re-growth are considered to be the main approaches for neural regeneration. In our previous study, a small molecular drug, chloroquine (CQ), protect the neurons through reducing the inflammation by inhibiting the NF-κB pathway. A macromolecular protein drug, FGF10 was available for treat SCI by inhibiting cell apoptosis, stimulating microtubules stabilize. It’s supposed FGF10 and CQ were delivered together, in coordination with rehabilitation training, may show obvious synergistic reaction. However, in view of the different physiochemical characteristics of FGF10 and CQ, current evidence is lacking to deliver together with high efficiency. In this project, a new CSPGs-targeted liposome (CAQK-Lip) in the silk fibroin (SF) hydrogel to encapsulate simultaneously FGF10 and CQ will be designed. Combine with in situ injection to form a three-dimensional supporting gel and weight-loss platform training, the synergistic effect and mechanism with multiple comprehensive evaluation system in SCI models will be investigated, by various molecular biological methods and omics technologies. This project utilizes targeted delivery system to deliver two different drugs, combined with rehabilitation training, to exert multiple effects in the treatment of SCI, which will provide a new therapeutic strategy for SCI.