Intra-mitochondrial Disulfide Polymerization Controls Cancer Cell Necroptosis

Abstract

The energy consuming reactions to biological dissipative state are ubiquitous in biological system, and its mimicry is a great challenge in synthetic chemistry. Herein, we developed intra-mitochondrial polymerization strategy for constructing macroscopic structures by ROS-dissipative system. For the first time, we found that disulfide polymerization is occurred inside cancer mitochondria owing to high ROS concentration of cancer mitochondria, while the disulfide polymerization is hardly happened inside cell due to intracellularly reductive environment. Polymerization process of thiol-containing monomer increases ROS inside mitochondria, which enable the autocatalytic process to accelerate further polymerization and induce mitochondrial dysfunction. This in-situ polymerization shows great potential for anticancer treatment against various cancer cell lines including drug resistant cancer cell.