Intra-Mitochondrial Polymerization-induced Self-Assembly using Dynamic Disulfide Bond for Anti-Cancer Treatment

Abstract

The potential use of intracellular polymerization could be new strategy in cancer theranostics. However, the regulation of polymerization has been still challenging due to spatiotemporal control. Unexpected polymerization can cause cellular damage on normal cells, decrease efficiency of intra-mitochondrial polymerization. In this regards, polymerization consisted of reversible bond would be beneficial due to easily decomposable property, reducing side effect. Disulfide bonds are one of dynamic covalent bonds used in the generation of reversible chemical systems. Under slightly basic condition, thiol group are deprotonated to give thiolate which are oxidized to disulfide. The disulfide bond can be decomposed easily into thiolate group under reduced environment. The high concentration and elevated level of ROS provide effective condition to occur polymerization inside mitochondria of cancer cells. However, low concentration and low level of ROS in normal mitochondria might not be sufficient for polymerization occurrence. In cancer cells, the resulting polymer stress mitochondria, leading to generation of ROS. The oxidative agents catalyze production of a larger amount of polymer, which generates more oxidative agent as autocatalytic emergency, leading to dysfunction of mitochondria.