Abstract：
Chemodynamic therapy (CDT) involving the use of metal nanozymes presents new opportunities for the treatment of deep-seated tumors. However, the lower ROS catalytic rate and dependence on high H2O2 concentrations affect therapeutic efficacy. To address this issue, a hydrogel was constructed for the treatment of osteosarcoma by combining Cu-Fe3O4 nanozymes (NCs) and artemisinin (AS) coencapsulated in situ with sodium alginate (ALG) and calcium ions. This hydrogel can release nanoparticles and AS within tumor tissue for an extended period of time, utilizing the multienzyme activity of NCs to achieve ROS accumulation. The carbon radicals (•C) generated from the interaction of Fe2+/Cu2+ with AS amplify oxidative stress, leading to tumor cell damage. Simultaneously, the NCs activate ferroptosis via the GPX4 pathway by depleting GSH and activate cuproptosis via the DLAT pathway by causing intracellular copper overload, enhancing therapeutic efficacy. In vitro experiments confirmed that the NCs-AS-ALG hydrogel has an excellent tumor cell killing effect, while in vivo experimental results demonstrated that it can effectively eliminate tumors with excellent biocompatibility, providing a new approach for osteosarcoma treatment.
摘要：
涉及使用金属纳米酶的化学动力学疗法（CDT）为治疗深层肿瘤提供了新的机会。然而,较低的ROS催化速率和对高H2O2浓度的依赖性影响治疗效果。为了解决这个问题，通过将Cu-Fe3O4纳米酶（NCs）和青蒿素（AS）与海藻酸钠（ALG）和钙离子原位共封装，构建了用于治疗骨肉瘤的水凝胶。这种水凝胶可以在肿瘤组织内长时间释放纳米颗粒和AS，利用NCs的多酶活性实现ROS积累。Fe2+/Cu2+与AS相互作用产生的碳自由基(•C)放大了氧化应激,导致肿瘤细胞损伤。同时,NCs通过消耗GSH通过GPX4途径激活铁凋亡，并通过引起细胞内铜过载通过DLAT途径激活铜凋亡，增强治疗效果。体外实验证实NCs-AS-ALG水凝胶具有优异的肿瘤细胞杀伤作用,而体内实验结果表明，它可以有效地消除肿瘤，具有优异的生物相容性，为骨肉瘤的治疗提供了新的途径。
