Wang Zhaoyang, Li Zekai, Shi Yuehua, Zeng Leyong
Key Laboratory of Medicinal Chemistry and Molecular Diagnosis of the Ministry of Education, Chemical Biology Key Laboratory of Hebei Province, State Key Laboratory of New Pharmaceutical Preparations and Excipients, College of Chemistry and Materials Science, Hebei University, Baoding 071002, P.R. China.
Regen Biomater. 2023 Sep 22;10:rbad087. doi: 10.1093/rb/rbad087. eCollection 2023.
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 (MnO) 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 MnO shell effectively avoided the leakage of DOX. However, in TME, the overexpressed glutathione (GSH) degraded MnO shell, which caused the DOX release. Moreover, the photothermal effect of MPDA and the Fenton-like reaction of the generated Mn further accelerated the cell death. Thus, the developed MPDA-DOX@MnO nanoplatform can intelligently modulate the release of DOX, and the combined CDT/PTT/chemotherapy possessed high-safety and high-efficacy against tumors.
药物从纳米载体中的非特异性泄漏严重削弱了化疗的安全性和有效性，构建肿瘤微环境（TME）响应型递送纳米载体、实现药物的调控释放至关重要。在此，以二氧化锰（MnO）作为守门人，开发了一种基于介孔聚多巴胺（MPDA）的智能纳米平台用于递送阿霉素（DOX），借此精确控制DOX的释放，同时实现光热疗法（PTT）和化学动力学疗法（CDT）。在正常生理环境中，稳定的MnO壳层有效避免了DOX的泄漏。然而，在TME中，过表达的谷胱甘肽（GSH）降解了MnO壳层，从而导致DOX释放。此外，MPDA的光热效应以及所生成的Mn的类芬顿反应进一步加速了细胞死亡。因此，所开发的MPDA-DOX@MnO纳米平台能够智能调控DOX的释放，并且联合CDT/PTT/化疗对肿瘤具有高安全性和高效性。
