Oxidative Polymerization in Living Cells

Yiheng Dai, Tianyu Li, Zhiheng Zhang, Yizheng Tan, Shuojiong Pan, Luo Zhang, and Huaping Xu

J. Am. Chem. Soc.2021, 143, 10709.

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.