Intracellular Polymerization-induced Self-Assembly for Supramolecular Approach to Control Cellular Fate

Abstract

The polymerization-induced artificial assembly of synthetic building units inside a living cell and the interaction of these assembly with the cellular components have rarely been studied, but are emerging as an intriguing strategy to control cellular fate. We developed intra-mitochondrial polymerization induced self-assembly (Mito-PISA) strategy for constructing polymeric structures by ROS-dissipative system. Targeting mitochondria, the vital organelle for cell survival, has been recognized as an efficient strategy in different therapeutic techniques by disturbing the normal function. Recently, we reported that intra-mitochondrial assembly induced the dysfunction of mitochondria by disrupting the membrane, resulting in the selective apoptosis of cancer cells. In addition, we described a mitochondria-targeting biomineralization system that favorably can induce silicification and consequent apoptosis of various cancer cells. Herein, we report that the in situ disulfide polymerization inside mitochondria is based on both large accumulation of monomers (increased local concentration for polymerization) and high ROS environment (chemical fuel for disulfide reaction). During the polymerization in a mitochondrial reducing environment, the autocatalytic process enables the continuous generation of ROS and the construction of bulky structures for mitochondrial dysfunction. This in-situ polymerization shows great potential for anticancer treatment against various cancer cell lines including drug resistant cancer cell. To the best of our knowledge, this is the first example showing intracellular polymerization to cause mitochondrial dysfunction and these findings can provide a new insight into intracellular polymerization and assembly for the regulation of cellular functions and a therapeutic approach and new targeting platform for the biomedical community.