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An Acidity‐Unlocked Magnetic Nanoplatform Enables Self‐Boosting ROS Generation through Upregulation of Lactate for Imaging‐Guided Highly Specific Chemodynamic Therapy
Author(s) -
Shi Linan,
Wang Youjuan,
Zhang Cheng,
Zhao Yan,
Lu Chang,
Yin Baoli,
Yang Yue,
Gong Xiangyang,
Teng Lili,
Liu Yanlan,
Zhang Xiaobing,
Song Guosheng
Publication year - 2021
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.202014415
Subject(s) - chemistry , downregulation and upregulation , reactive oxygen species , intracellular , oxidative stress , catalysis , in vivo , cancer therapy , tumor microenvironment , biophysics , cancer research , microbiology and biotechnology , biochemistry , cancer , tumor cells , biology , medicine , gene
Chemodynamic therapy is an emerging tumor therapeutic strategy. However, the anticancer effects are greatly limited by the strong acidity requirements for effective Fenton‐like reaction, and the inevitably “off‐target” toxicity. Herein, we develop an acidity‐unlocked nanoplatform (FePt@FeO x @TAM‐PEG) that can accurately perform the high‐efficient and tumor‐specific catalysis for anticancer treatment, through dual pathway of cyclic amplification strategy. Notably, the pH‐responsive peculiarity of tamoxifen (TAM) drug allows for the catalytic activity of FePt@FeO x to be “turn‐on” in acidic tumor microenvironments, while keeping silence in neutral condition. Importantly, the released TAM within cancer cells is able to inhibit mitochondrial complex I, leading to the upregulated lactate content and thereby the accumulated intracellular H + , which can overcome the intrinsically insufficient acidity of tumor. Through the positive feedback loop, large amount of active FePt@FeO x nanocatalyzers are released and able to access to the endogenous H 2 O 2 , exerting the improved Fenton‐like reaction within the more acidic condition. Finally, such smart nanoplatform enables self‐boosting generation of reactive oxygen species (ROS) and induces strong intracellular oxidative stress, leading to the substantial anticancer outcomes in vivo, which may provide a new insight for tumor‐specific cascade catalytic therapy and reducing the “off‐target” toxicity to surrounding normal tissues.