In situ-transition nanozyme triggered by tumor microenvironment boosts synergistic cancer radio-/chemotherapy through disrupting redox homeostasis. (August 2022)

• Record Type: Journal Article
• Authors: Yuan, Zhongwen; Liu, Xinxin; Ling, Jiabao; Huang, Guanning; Huang, Jiarun; Zhu, Xueqiong; He, Lizhen; Chen, Tianfeng
• Is Part Of: Biomaterials. Volume 287(2022)
• Publication Date: 2022-08
• Subjects: Radiotherapy -- Tumor microenvironment -- Mn -- Nanozyme -- Redox balance -- Radiosensitization; Biomedical materials -- Periodicals; Biocompatible Materials -- Periodicals; Biomatériaux -- Périodiques; 610.28
• DOI: 10.1016/j.biomaterials.2022.121620
• Languages: English
• ISSNs: 0142-9612

Abstract

Abstract: Disrupting redox homeostasis in the tumor microenvironment (TME), like excessive H2 O2, glutathione (GSH) and weak acidity, has been proved as an effective tumor therapeutic strategy. Herein, we constructed a TME-responsive nanozyme, DOX@HMSN/Mn3 O4 (R), with reversible Mn 3+ /Mn 2+ transition in situ triggered by TME to perturb the intrinsic redox homeostasis and catalyze reactive oxygen species (ROS) overproduction. In addition, this nanozyme could react with excess GSH in TME to produce GSSG, resulting in the consumption of reducing agents to suppress ROS clearance. Density functional theory calculations further confirmed that the nanozyme mainly exhibited the oxidase-like activity to catalyze the formation of hydroxyl radicals from O2, thus strengthening the oxidation environment in the TME. Combined with radiotherapy, the high-energy X-ray could excite the outer-layer electrons in the nanozyme, forming photoelectrons that participate in the oxidase-like enzymatic reaction, thus intensifying ROS accumulation and amplifying the radio-/chemotherapeutic efficacy.