Cancer-Selective Supramolecular Chemotherapy by Disassembly-Assembly Approach

M. T. Jeena, Seongeon Jin, Keunsoo Jeong, Yuri Cho, Jin Chul Kim, Jeong Hyeon Lee, Seokyoung Lee, Suk Won Hwang, Sang Kyu Kwak, Sehoon Kim, Ja Hyoung Ryu

Research output: Contribution to journalArticlepeer-review

Abstract

Intramitochondrial supramolecular assembly can be a new therapeutic strategy for treating cancer because mitochondria are the key for virtually all facets of the tumorigenesis. However, the in vivo applications of mitochondria-targeting molecules are limited due to the positive charge and hydrophobicity that should be possessed by these molecules to penetrate the mitochondrial membrane, which may induce nonspecific serum protein interactions and normal cell accumulation. Herein, a stimuli-responsive mitochondria-targeting molecule, Mito-SA that forms nano-sized micelles under physiological conditions is presented. In the aggregated state, the succinic amide bonds in Mito-SA are cleaved in response to tumoral pH by stabilizing the transition state through the intermolecular interactions and the micelle disassembles into a mitochondria-targeting parent molecule, Mito-FF. The Mito-FF accumulate inside cancer mitochondria to induce cell death by intra-mitochondrial self-assembly into fiber structures. This tumoral stimuli-responsive disassembly–assembly approach will provide insight to develop mitochondria targeted supramolecular anticancer agent with high tumoral specificity.

Original languageEnglish
Article number2208098
JournalAdvanced Functional Materials
Volume32
Issue number52
DOIs
Publication statusPublished - 2022 Dec 22

Keywords

  • assembly-disassembly
  • cancer cell death
  • enhanced specificities
  • intra-mitochondrial assemblies
  • pH stimuli

ASJC Scopus subject areas

  • Chemistry(all)
  • Materials Science(all)
  • Condensed Matter Physics

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