Intracellular Construction of Topological Polymer Networks to Destruct Organelles

Topological polymers play a major role in their interaction with intracellular organelles to affect their cellular activities owing to their large surface area and multilevel branched structures. Yet, the existing studies on these polymers mainly focus on the topochemical polymerization outside the cells and how these topological polymers interact with the cell outer membrane. Herein, we established an intracellular topological polymerization based on the 2′-Te modified oligonucleotides (DNA-Te2), containing two tellurium as polymerization active sites that undergo oxidative polymerization inside living cells. The highly oxidized polytelluoxane effectively disturbed antioxidant systems by an interaction between Te (IV) and selenoproteins, thus leading to the effective inhibition of cancer cells. More importantly, the generated topological polymer networks were shown to interfere with organelles in cells, effectively affecting the substrate communication between organelles and the cytoplasm, eventually modulating their cellular behavior and killing cancer cells. Biological evaluation showed that our strategy exhibited efficient tumor inhibition effect and good biosafety. Ultimately, we believe our approach provides a new possibility for chemists and biologists to manipulate cellular activity in the realm of topological polymerization.