药物从纳米载体中的非特异性渗漏严重削弱了化疗的安全性和有效性，构建肿瘤微环境（TME）响应性的递送纳米载体、实现药物的调节释放至关重要。本文以二氧化锰（MnO2）为看门人，开发了一种基于介孔聚多巴胺（MPDA）的智能纳米平台来递送阿霉素（DOX），精确控制DOX的释放，同时进行光热治疗（PTT）和化学动力学治疗（CDT）已实现。在正常生理环境下，稳定的MnO2外壳有效避免了DOX的泄漏。然而，在 TME 中，过表达的谷胱甘肽 (GSH) 降解了 MnO2 壳，导致 DOX 释放。此外，MPDA的光热效应和生成的Mn2的类芬顿反应进一步加速了细胞死亡。因此，所开发的MPDA-DOX@MnO2纳米平台可以智能调节DOX的释放，并且CDT/PTT/化疗联合疗法具有高安全性和高疗效的抗肿瘤效果。©作者2023。牛津大学出版社出版。

The non-specific leakage of drugs from nanocarriers seriously weakened the safety and efficacy of chemotherapy, and it was very critical of constructing tumor microenvironment (TME)-responsive delivery nanocarriers, achieving the modulation release of drugs. Herein, using manganese dioxide (MnO2) as gatekeeper, an intelligent nanoplatform based on mesoporous polydopamine (MPDA) was developed to deliver doxorubicin (DOX), by which the DOX release was precisely controlled, and simultaneously the photothermal therapy (PTT) and chemodynamic therapy (CDT) were realized. In normal physiological environment, the stable MnO2 shell effectively avoided the leakage of DOX. However, in TME, the overexpressed glutathione (GSH) degraded MnO2 shell, which caused the DOX release. Moreover, the photothermal effect of MPDA and the Fenton-like reaction of the generated Mn2+ further accelerated the cell death. Thus, the developed MPDA-DOX@MnO2 nanoplatform can intelligently modulate the release of DOX, and the combined CDT/PTT/chemotherapy possessed high-safety and high-efficacy against tumors.© The Author(s) 2023. Published by Oxford University Press.