Intracellular polymerization and self-assembly to control cellular fate

Abstract

The endeavor efforts to cure the cancer have been made to develop cytotoxic chemotherapy, targeted chemotherapy, to immunotherapy. However, the cytotoxic chemotherapy has severe side effects to kill healthy normal cells, and targeted chemotherapy which inhibits specific cancer proteins has a drug resistance problem, and immunotherapy is only applicable for limited patient. Therefore, it is highly demanded to develop a new paradigm of cancer therapy. Our research team has focused the efforts on the development of new cancer therapy using supramolecular approach through molecular design based on the knowledge of supramolecular chemistry. In this talk, I would like to discuss about mitochondria-targeted supramolecular therapeutics. 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. 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.