【摘要】 利用原位自由基聚合反应设计合成了葡萄糖氧化酶纳米胶囊(nGOx)和负载替拉扎明(TPZ)的介孔二氧化硅纳米胶囊(nMSNs-TPZ),具有交联结构的聚合物壳层赋予GOx与MSNs-TPZ更高的稳定性与更长的瘤内滞留时间. nGOx持续增强的肿瘤乏氧微环境能够促使TPZ转化为具有细胞毒性的自由基,二者协同作用增强了肿瘤治疗的效果.研究结果表明, nGOx与nMSNs-TPZ均具有尺寸均一的球形结构. nGOx在胰蛋白酶、特定温度以及不同pH溶液中的稳定性均有显著提升,并展现出良好的催化活性. nMSNs-TPZ在谷胱甘肽（GSH）存在下能够有效降解，实现TPZ的可控释放.体外细胞实验和体内动物实验均证实, nGOx产生的局部乏氧环境更有利于TPZ发挥作用,两者的协同治疗展现出更优越的抑瘤效果.更多还原

【Abstract】 In this study, glucose oxidase nanocapsules(nGOx) and mesoporous silica nanocapsules loaded with tirapazamide(nMSNs-TPZ) were designed and synthesized using in situ radical polymerization reactions. The crosslinked polymer shell structure provided GOx and MSNs-TPZ with higher stability and longer tumor retention time. The sustained enhancement of the tumor hypoxic microenvironment by nGOx promoted the conversion of TPZ into cytotoxic free radicals, enhancing the therapeutic efficacy of tumor treatment through synergistic effects. Both n GOx and nMSNs-TPZ were found to have spherical structures with uniform sizes. nGOx exhibited significantly improved stability and good catalytic activity in trypsin, specific temperatures, and different pH solutions. On the other hand, nMSNs-TPZ could be efficiently degraded in the presence of GSH, allowing for the controlled release of TPZ. In vitro cellular experiments and in vivo animal studies confirmed that the local hypoxic environment generated by nGOx was more favorable for TPZ to exert its effects. The synergistic treatment of the two nanocapsules shows superior tumor suppression effects. Therefore, this therapeutic strategy holds promise as another potential method for tumor treatment.更多还原