Chang Meiqi, Wang Zeyu, Dong Caihong, Zhou Ruirui, Chen Liang, Huang Hui, Feng Wei, Wang Ziliang, Wang Yin, Chen Yu
Central Laboratory of Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 200071, P. R. China.
State Key Laboratory of High-Performance Ceramics and Superfine Microstructure, Shanghai Institute of Ceramics, Chinese Academy of Sciences, Shanghai, 200050, P. R. China.
Adv Mater. 2023 Feb;35(7):e2208817. doi: 10.1002/adma.202208817. Epub 2022 Dec 18.
Overcoming apoptosis resistance to achieve efficient breast cancer treatment remains a challenge. The precise induction of another form of programmed cell death, pyroptosis, is an excellent alternative for treating cancer. Ultrasound (US)-enhanced enzyme dynamic (enzyodynamic) therapy is developed by employing LaFeO (LFO) perovskite nanocrystals as a substrate to increase the rate of deleterious reactive oxygen species (ROS) generation for intensive cell pyroptosis. LFO nanocrystals possess quadruple enzyme-mimicking activities, including oxidase-, peroxidase-, glutathione peroxidase-, and catalase-mimicking activities, which undertake the dominant therapeutic task through cascade catalytic reactions, including the reversal of hypoxic microenvironment, depletion of endogenous glutathione, and continuous output of ROS. US exogenous stimulation increases the transition rate of the intermediate complex to Fe (II) and favors incremental ROS production, by which the ROS burst-induced pyroptosis process is accomplished through the ROS-TXNIP-NLRP3-GSDMD pathway. Both in vitro and in vivo antineoplastic outcomes affirm the ascendancy of LFO nanozyme-induced pyroptosis. This work highlights the critical role of US coupled with nanocatalytic reactors in pyroptosis-dominant breast cancer treatment with the apoptosis resistance circumvention feature.
克服凋亡抗性以实现有效的乳腺癌治疗仍然是一项挑战。精确诱导另一种形式的程序性细胞死亡——焦亡，是治疗癌症的一种极佳选择。超声（US）增强酶动力学（酶动力）疗法是通过使用LaFeO（LFO）钙钛矿纳米晶体作为底物来提高有害活性氧（ROS）的生成速率，从而实现强烈的细胞焦亡。LFO纳米晶体具有四重酶模拟活性，包括氧化酶、过氧化物酶、谷胱甘肽过氧化物酶和过氧化氢酶模拟活性，它们通过级联催化反应承担主要治疗任务，包括逆转缺氧微环境、消耗内源性谷胱甘肽以及持续输出ROS。US外源刺激增加了中间复合物向Fe（II）的转变速率，并有利于ROS的增量产生，通过ROS-TXNIP-NLRP3-GSDMD途径完成ROS爆发诱导的焦亡过程。体外和体内的抗肿瘤结果都证实了LFO纳米酶诱导焦亡的优势。这项工作突出了US与纳米催化反应器在具有凋亡抗性规避特征的以焦亡为主的乳腺癌治疗中的关键作用。
