4.8 Article

Oxidative Polymerization in Living Cells

Journal

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
Volume 143, Issue 28, Pages 10709-10717

Publisher

AMER CHEMICAL SOC
DOI: 10.1021/jacs.1c04821

Keywords

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Funding

  1. National Basic Research Plan of China [2018YFA208900]
  2. National Natural Science Foundation of China [21734004]
  3. Foundation for Innovative Research Groups of the National Natural Science Foundation of China [21821001]

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This study demonstrates a novel oxidative polymerization reaction in cells triggered by intracellular ROS, selectively inducing apoptosis in cancer cells. The polymerization products disrupt intracellular antioxidant systems, leading to increased oxidative stress, further promoting oxidative polymerization and activating apoptosis pathways related to ROS. The anticancer efficacy and biosafety of this strategy are proven in vitro and in vivo, suggesting a new possibility for chemists to manipulate cellular behavior through artificial chemical reactions.
Intracellular polymerization is an emerging technique that can potentially modulate cell behavior, but remains challenging because of the complexity of the cellular environment. Herein, taking advantage of the chemical properties of organotellurides and the intracellular redox environment, we develop a novel oxidative polymerization reaction that can be conducted in cells without external stimuli. We demonstrate that this polymerization reaction is triggered by the intracellular reactive oxygen species (ROS), thus selectively proceeding in cancer cells and inducing apoptosis via a unique self-amplification mechanism. The polymerization products are shown to disrupt intracellular antioxidant systems through interacting with selenoproteins, leading to greater oxidative stress that would further the oxidative polymerization and eventually activate ROS-related apoptosis pathways. The selective anticancer efficacy and biosafety of our strategy are proven both in vitro and in vivo. Ultimately, this study enables a new possibility for chemists to manipulate cellular proliferation and apoptosis through artificial chemical reactions.

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