한빛사논문
Sangpil Kim‡, Batakrishna Jana‡, Eun Min Go‡, Ji Eun Lee, Seongeon Jin, Eun-Koung An, Juyoung Hwang, Youjung Sim, Sehee Son, Dohyun Kim, Chaekyu Kim, Jun-O Jin*, Sang Kyu Kwak*, Ja-Hyoung Ryu*
*Corresponding Authors
Ja-Hyoung Ryu
Department of Chemistry, Ulsan National Institute of Science and Technology (UNIST), Ulsan 44919, Republic of Korea
Sang Kyu Kwak
Department of Energy Engineering, School of Energy and Chemical Engineering, Ulsan National Institute of Science and Technology (UNIST), Ulsan 44919, Republic of Korea;
Jun-O Jin
Department of Medical Biotechnology, Yeungnam University, Gyeongsan 38541, South Korea;
Sangpil Kim - Department of Chemistry, Ulsan National Institute of Science and Technology (UNIST), Ulsan 44919, Republic of Korea
Batakrishna Jana - Department of Chemistry, Ulsan National Institute of Science and Technology (UNIST), Ulsan 44919, Republic of Korea
Eun Min Go - Department of Energy Engineering, School of Energy and Chemical Engineering, Ulsan National Institute of Science and Technology (UNIST), Ulsan 44919, Republic of Korea
Ji Eun Lee - Department of Energy Engineering, School of Energy and Chemical Engineering, Ulsan National Institute of Science and Technology (UNIST), Ulsan 44919, Republic of Korea
Seongeon Jin - Department of Chemistry, Ulsan National Institute of Science and Technology (UNIST), Ulsan 44919, Republic of Korea
Eun-Koung An - Department of Medical Biotechnology and Research Institute of Cell Culture, Yeungnam University, Gyeongsan 38541, South Korea
Juyoung Hwang - Department of Medical Biotechnology and Research Institute of Cell Culture, Yeungnam University, Gyeongsan 38541, South Korea
Youjung Sim - Department of Chemistry, Ulsan National Institute of Science and Technology (UNIST), Ulsan 44919, Republic of Korea
Sehee Son - Department of Chemistry, Ulsan National Institute of Science and Technology (UNIST), Ulsan 44919, Republic of Korea
Dohyun Kim - Department of Chemistry, Ulsan National Institute of Science and Technology (UNIST), Ulsan 44919, Republic of Korea
Chaekyu Kim - Department of Chemistry, Ulsan National Institute of Science and Technology (UNIST), Ulsan 44919, Republic of Korea
Author Contributions
‡S.K., B.J., and E.M.G. contributed equally to this work.
Abstract
Recent advances in supramolecular chemistry research have led to the development of artificial chemical systems that can form self-assembled structures that imitate proteins involved in the regulation of cellular function. However, intracellular polymerization systems that operate inside living cells have been seldom reported. In this study, we developed an intramitochondrial polymerization-induced self-assembly system for regulating the cellular fate of cancer cells. It showed that polymeric disulfide formation inside cells occurred due to the high reactive oxygen species (ROS) concentration of cancer mitochondria. This polymerization barely occurs elsewhere in the cell owing to the reductive intracellular environment. The polymerization of the thiol-containing monomers further increases the ROS level inside the mitochondria, thereby autocatalyzing the polymerization process and creating fibrous polymeric structures. This process induces dysfunction of the mitochondria, which in turn activates cell necroptosis. Thus, this in situ polymerization system shows great potential for cancer treatment, including that of drug-resistant cancers.
KEYWORDS : disulfide bond, intramitochondrial polymerization, polymerization induced self-assembly, cancer reactive oxygen species
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