Intra-mitochondrial disulfide polymerization controls cancer cell necroptosis

Abstract In a biological system, energy-consuming reactions to attain a biological dissipative state are ubiquitous, and mimicking such reactions is a great challenge in synthetic chemistry. Herein, we report an intra-mitochondrial polymerization strategy for constructing macroscopic structures using a reactive oxygen species (ROS)-dissipative system. This is the first time that the occurrence of disulfide polymerization inside cancer mitochondria owing to the high ROS concentration of cancer mitochondria is reported. This polymerization hardly occurred inside cells owing to the intracellular reductive environment. The polymerization process of a thiol-containing monomer further increases the ROS level inside the mitochondria, thereby enabling the autocatalytic process to accelerate polymerization and induce mitochondrial dysfunction. This in-situ polymerization shows great potential for anticancer treatment against various cancer cell lines, including drug-resistant cancer cells.