High-Performance Self-Cascade Pyrite Nanozymes for Apoptosis–Ferroptosis Synergistic Tumor Therapy

作者：Xiangqin Meng, Dandan Li, Lei Chen, Helen He, Qian Wang, Chaoyi Hong, Jiuyang He, Xingfa Gao, Yili Yang, Bing Jiang, Guohui Nie, Xiyun Yan, Lizeng Gao, Kelong Fan · 发表于：ACS Nano · 年份：2021 · DOI：10.1021/acsnano.1c01248 · 被引用次数：468 · 研究领域：Advanced Nanomaterials in Catalysis、Nanoplatforms for cancer theranostics、Nanocluster Synthesis and Applications

As next-generation artificial enzymes, nanozymes have shown great promise for tumor catalytic therapy. In particular, their peroxidase-like activity has been employed to catalyze hydrogen peroxide (H 2 O 2 ) to produce highly toxic hydroxyl radicals ( • OH) to kill tumor cells. However, limited by the low affinity between nanozymes with H 2 O 2 and the low level of H 2 O 2 in the tumor microenvironment, peroxidase nanozymes usually produced insufficient • OH to kill tumor cells for therapeutic purposes. Herein, we present a pyrite peroxidase nanozyme with ultrahigh H 2 O 2 affinity, resulting in a 4144- and 3086-fold increase of catalytic activity compared with that of classical Fe 3 O 4 nanozyme and natural horseradish peroxidase, respectively. We found that the pyrite nanozyme also possesses intrinsic glutathione oxidase-like activity, which catalyzes the oxidation of reduced glutathione accompanied by H 2 O 2 generation. Thus, the dual-activity pyrite nanozyme constitutes a self-cascade platform to generate abundant • OH and deplete reduced glutathione, which induces apoptosis as well as ferroptosis of tumor cells. Consequently, it killed apoptosis-resistant tumor cells harboring KRAS mutation by inducing ferroptosis. The pyrite nanozyme also exhibited favorable tumor-specific cytotoxicity and biodegradability to ensure its biosafety. These results indicate that the high-performance pyrite nanozyme is an effective therapeutic reagent and may aid the development of nanozyme...