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

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. 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. The oxidative agents catalyze production of a larger amount of polymer, which generates more oxidative agent as autocatalytic emergency, leading to dysfunction of mitochondria.