4.8 Article

Specific Unlocking of a Nanozyme-Based Butterfly Effect To Break the Evolutionary Fitness of Chaotic Tumors

Journal

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
Volume 59, Issue 24, Pages 9491-9497

Publisher

WILEY-V C H VERLAG GMBH
DOI: 10.1002/anie.201916142

Keywords

antitumor agents; butterfly effect; chaotic tumors; iridium oxide; parallel cascade reactions

Funding

  1. Joint Sino-German Research Projects [21761132028]
  2. National Natural Science Foundation of China [21675149, 21874125, 21877107]
  3. Key Research Program of Frontier Sciences, CAS [QYZDY-SSW-SLH019]
  4. Science and Technology Development Program of Jilin Province [20170414037GH, 20190201074JC, 20180101015JC]
  5. K. C. Wong Education Foundation

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Chaos and the natural evolution of tumor systems can lead to the failure of tumor therapies. Herein, we demonstrate that iridium oxide nanoparticles (IrOx) possess acid-activated oxidase and peroxidase-like functions and wide pH-dependent catalase-like properties. The integration of glucose oxidase (GOD) unlocked the oxidase and peroxidase activities of IrOx by the production of gluconic acid from glucose by GOD catalysis in cancer cells, and the produced H2O2 was converted into O-2 to compensate its consumption in GOD catalysis owing to the catalase-like function of the nanozyme, thus resulting in the continual consumption of glucose and the self-supply of substrates to generate superoxide anion and hydroxyl radical. Moreover, IrOx can constantly consume glutathione (GSH) by self-cyclic valence alternation of Ir-IV and Ir-III. These cascade reactions lead to a butterfly effect of initial starvation therapy and the subsequent pressure of multiple reactive oxygen species (ROS) to completely break the self-adaption of cancer cells.

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