动态交联水凝胶负载二硫化钼和抗氧化剂用于肿瘤性骨缺损修复的体外研究

In Vitro Investigation of a Dynamically Crosslinked Hydrogel Incorporating Molybdenum Disulfide and Antioxidants for Tumorous Bone Defect Repair

摘要: 针对骨肉瘤术后高复发及缺损部位氧化应激难题，利用水凝胶作为药物递送载体，设计并制备集光热抗肿瘤与抗氧化功能于一体的MAEO复合纳米水凝胶。该水凝胶以席夫碱键和离子络合动态交联改性透明质酸与海藻酸钠为基质，物理掺杂二硫化钼(MoS₂)纳米花作为光热剂，同时负载表没食子儿茶素没食子酸酯(EGCG)为抗氧化剂。在1064 nm近红外光照射下，含100 μg/mL MoS₂的水凝胶可产生高效光热效应，显著杀伤肿瘤细胞，并保持良好的生物相容性。同时，负载的EGCG清除活性氧，降低局部炎症与氧化应激水平，有利于改善骨缺损微环境。MAEO水凝胶协同整合光热治疗与抗氧化药物，有望为肿瘤性骨缺损修复及术后防复发提供新策略。

Abstract: In order to solve the problems of high recurrence and oxidative stress in the defect site of osteosarcoma after operation, MAEO composite nano-hydrogel with photothermal anti-tumor and anti-oxidation functions was designed and prepared by using hydrogel as drug delivery carrier. The hydrogel matrix was prepared from modified hyaluronic acid and sodium alginate through dynamic Schiff base bonding and ionic coordination crosslinking. Molybdenum disulfide (MoS₂) nanoflowers were physically incorporated as photothermal agents, while epigallocatechin gallate (EGCG) was loaded as a potent antioxidant. Upon 1064 nm near-infrared (NIR) laser irradiation, the hydrogel containing 100 μg/mL MoS₂ exhibited an efficient photothermal conversion effect, resulting in significant tumor cell ablation while maintaining favorable biocompatibility. Meanwhile, the released EGCG effectively scavenged reactive oxygen species (ROS), thereby alleviating local inflammation and oxidative stress and contributing to the improvement of the bone defect microenvironment. By synergistically integrating photothermal therapy with antioxidative drug delivery, the MAEO hydrogel demonstrates considerable potential as a therapeutic strategy for postoperative prevention of osteosarcoma recurrence and tumorous bone defect repair.