Self-cascade nanohybrids boost cell ferroptosis stress for tumor radiosensitization therapy. (December 2022)

• Record Type: Journal Article
• Authors: Wu, Qinghe; Hou, Mengfei; Zhang, Pengli; Jiang, Yifei; Liu, Meirong; Xiong, Liqin; Hai, Wangxi; Zhang, Min; Li, Xiao; Li, Biao; Zhang, Chunfu
• Is Part Of: Applied materials today. Volume 29(2022)
• Publication Date: 2022-12
• Subjects: Self-cascade nanozyme -- Glucose oxidase-mimicking activity -- Ferroptosis -- Tumor microenvironment -- Radiosensitization therapy; Materials science -- Periodicals; Materials -- Research -- Periodicals; 620.1105
• DOI: 10.1016/j.apmt.2022.101558
• Languages: English
• ISSNs: 2352-9407

Abstract

Highlights: A novel nanohybrid composed of MnO2 nanodots and bovine serum albumin (BSA)-coated Au nanoclusters (BAM) was fabricated as a high-performance radiosensitizer. The ultrasmall MnO2 nanodots possessed fascinating glucose oxidase-mimicking property and "four-in-one" catalytic activities. The nanohybrids could initiate self-cascade catalysis to reprogram tumor cell fate to ferroptosis and reshape tumor microenvironment, efficiently sensitizing radiotherapy of tumors. Abstract: Although ferroptosis plays a potential role in sensitizing tumor radiotherapy, its radiosensitization efficacy is still limited by insufficient endogenous H2 O2 and excess glutathione (GSH) in the tumor microenvironment (TME). Herein, we engineered a "four-in-one" self-cascade nanohybrid composed of MnO2 nanodots-encompassed and bovine serum albumin (BSA)-coated gold nanoclusters (BAM) for radiosensitization therapy of tumors by reprogramming tumor cell fate to ferroptosis and reshaping TME. The MnO2 nanodots possessed fascinating glucose oxidase (GOx)-mimicking activity to effectively catalyze tumor endogenous glucose into H2 O2, could further decompose H2 O2 into hydroxyl radicals (HO·) and O2 in response to acidic TME, and simultaneously depleted the endogenous GSH, breaking the redox homeostasis in TME. As a result, lipid peroxides (LPO) in cell membranes and ferroptosis stress of tumor cells were significantly up-regulated. Synergy with the hypoxia relief and enhancement by the gold nanocores, radiotherapy completely inhibited the tumor progression. Moreover, the gold nanocores were successfully radiolabeled with 64 Cu, and PET imaging revealed that BAM had high tumor-targeting efficiency and was renally clearable. Our study provides a unique perspective on radiosensitization therapy by regulating tumor cell fate to ferroptosis through rational design of a self-cascade nanozyme. Graphical abstract: Image, graphical abstract