血脑屏障（BBB）是一个复杂且高度限制性的屏障，可阻止大多数生物分子和药物进入大脑。然而，治疗胶质母细胞瘤迫切需要向大脑输送药物的有效策略。本工作基于脑转移性乳腺癌细胞（EB）来源的外泌体高效的血脑屏障穿透特性，制备了由Mn2+、砷酸盐和葡萄糖氧化酶（GOx）自组装构建的纳米反应器（记为MAG@EB）成用 EB 包裹的纳米颗粒。 MAG@EB 可以提高穿过 BBB 的效率，靶向并在原位胶质母细胞瘤位点积聚。 GOx 驱动的糖酵解有效地切断了葡萄糖的供应，同时还提供了大量的 H2O2 并降低了 pH 值。同时，释放的Mn2介导的类芬顿反应将升高的H2O2转化为剧毒的·OH。此外，AsV被谷胱甘肽还原为AsIII，AsIII激活抑癌基因P53，从而杀死胶质母细胞瘤细胞。体内和体外结果表明，胶质母细胞瘤会死于 MAG@EB 引发的氧化还原级联反应，产生显着的治疗效果。这项工作为未来治疗胶质母细胞瘤提供了一种由级联纳米反应器介导的有前景的治疗选择。版权所有 © 2024 Elsevier Ltd. 保留所有权利。

The blood-brain barrier (BBB) is a complex and highly restrictive barrier that prevents most biomolecules and drugs from entering the brain. However, effective strategies for delivering drugs to the brain are urgently needed for the treatment of glioblastoma. Based on the efficient BBB penetration properties of exosomes derived from brain metastatic breast cancer cells (EB), this work prepared a nanoreactor (denoted as MAG@EB), which was constructed by self-assembly of Mn2+, arsenate and glucose oxidase (GOx) into nanoparticles wrapped with EB. MAG@EB can enhance the efficiency of traversing the BBB, target and accumulate at in situ glioblastoma sites. The GOx-driven glycolysis effectively cuts off the glucose supply while also providing an abundance of H2O2 and lowering pH. Meanwhile, the released Mn2+ mediated Fenton-like reaction converts elevated H2O2 into highly toxic ·OH. Besides, AsV was reduced to AsIII by glutathione, and the tumor suppressor gene P53 was activated by AsIII to kill glioblastoma cells. Glioblastoma succumbed to the redox cascade triggered by MAG@EB, as the results demonstrated in vivo and in vitro, yielding a remarkable therapeutic effect. This work provides a promising therapeutic option mediated by cascaded nanoreactors for the future treatment of glioblastoma.Copyright © 2024 Elsevier Ltd. All rights reserved.