Intramitochondrial Polymerization-induced Self-Assembly (Mito-PISA) Using Covalent Bond Controls Cancer Cell Necrosis

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 an intra-mitochondrial polymerization strategy for constructing macroscopic structures by ROS-dissipative system. For the first time, we found that the disulfide polymerization occurred inside cancer mitochondria owing to the high ROS concentration of cancer mitochondria, while it is hardly happened inside cell due to intracellular reductive environment. Polymerization process of thiol-containing monomer further increases ROS level inside mitochondria, which enables 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 cell.