开发多功能、刺激响应的纳米药物很有趣，因为它具有有效治疗癌症的潜力。然而，纳米药物的肿瘤渗透性差导致抗肿瘤功效有限。在此，开发了一种负载MnO和CaO2纳米颗粒的氧驱动硅基纳米电机（Si-motor），它可以通过CaO2和MnO的级联反应在肿瘤微环境（TME）中移动。在酸性 TME 下，CaO2 与酸反应释放 Ca2 诱导线粒体损伤，同时产生 O2 和 H2O2，此时负载的 MnO 发挥芬顿样活性，在产生的 H2O2 的基础上产生·OH 和 O2。产生的 O2 驱动 Si 电机前进，从而赋予 TME 中形成的电机主动输送能力。同时，具有谷胱甘肽（GSH）消耗能力的MnO进一步防止活性氧（ROS）被破坏。这种 TME 驱动的 Si 马达具有增强的细胞摄取和深度渗透，可放大由细胞内 Ca2 超载、Mn2 诱导的 GSH 消耗和 Mn2 介导的化学动力学治疗 (CDT) 引起的协同氧化应激，从而导致出色的肿瘤细胞死亡。创建的纳米电机可以为主动协同癌症治疗提供有效的平台。© 2024 Wiley‐VCH GmbH。

Developing multifunctional, stimuli-responsive nanomedicine is intriguing because it has the potential to effectively treat cancer. Yet, poor tumor penetration of nanodrugs results in limited antitumor efficacy. Herein, an oxygen-driven silicon-based nanomotor (Si-motor) loaded with MnO and CaO2 nanoparticles is developed, which can move in tumor microenvironment (TME) by the cascade reaction of CaO2 and MnO. Under acidic TME, CaO2 reacts with acid to release Ca2+ to induce mitochondrial damage and simultaneously produces O2 and H2O2, when the loaded MnO exerts Fenton-like activity to produce ·OH and O2 based on the produced H2O2. The generated O2 drives Si-motor forward, thus endowing active delivery capability of the formed motors in TME. Meanwhile, MnO with glutathione (GSH) depletion ability further prevents reactive oxygen species (ROS) from being destroyed. Such TME actuated Si-motor with enhanced cellular uptake and deep penetration provides amplification of synergistic oxidative stresscaused by intracellular Ca2 + overloading, GSH depletion induced by Mn2+, and Mn2+ mediated chemodynamic treatment (CDT), leading to excellent tumor cell death. The created nanomotor may offer an effective platform for active synergistic cancer treatment.© 2024 Wiley‐VCH GmbH.