Molecular logistics using cytocleavable polyrotaxanes for the reactivation of enzymes delivered in living cells

Atsushi Tamura, Go Ikeda, Ji-Hun Seo, Koji Tsuchiya, Hirofumi Yajima, Yoshihiro Sasaki, Kazunari Akiyoshi, Nobuhiko Yui

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

The intracellular delivery of enzymes is an essential methodology to extend their therapeutic application. Herein, we have developed dissociable supermolecule-enzyme polyelectrolyte complexes based on reduction-cleavable cationic polyrotaxanes (PRXs) for the reactivation of delivered enzymes. These PRXs are characterized by their supramolecular frameworks of a polymeric chain threading into cyclic molecules, which can form polyelectrolyte complexes with anionic enzymes while retaining their three dimensional structure, although their enzymatic activity is reduced. Upon the addition of a reductant, the PRXs dissociate into their constituent molecules and release the enzymes, resulting in a complete recovery of enzymatic activity. Under the intracellular environment, the PRX-based enzyme complexes showed the highest intracellular enzymatic activity and efficient activation of anticancer prodrugs to induce cytotoxic effects in comparison with the non-dissociable complexes and the commercial cell-penetrating peptide-based reagents. Thus, the intracellularly dissociable supermolecules are an attractive system for delivering therapeutic enzymes into living cells.

Original languageEnglish
Article number2252
JournalScientific Reports
Volume3
DOIs
Publication statusPublished - 2013 Aug 5
Externally publishedYes

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Rotaxanes
Enzymes
Cell-Penetrating Peptides
Reducing Agents
Prodrugs

ASJC Scopus subject areas

  • General
  • Medicine(all)

Cite this

Molecular logistics using cytocleavable polyrotaxanes for the reactivation of enzymes delivered in living cells. / Tamura, Atsushi; Ikeda, Go; Seo, Ji-Hun; Tsuchiya, Koji; Yajima, Hirofumi; Sasaki, Yoshihiro; Akiyoshi, Kazunari; Yui, Nobuhiko.

In: Scientific Reports, Vol. 3, 2252, 05.08.2013.

Research output: Contribution to journalArticle

Tamura, Atsushi ; Ikeda, Go ; Seo, Ji-Hun ; Tsuchiya, Koji ; Yajima, Hirofumi ; Sasaki, Yoshihiro ; Akiyoshi, Kazunari ; Yui, Nobuhiko. / Molecular logistics using cytocleavable polyrotaxanes for the reactivation of enzymes delivered in living cells. In: Scientific Reports. 2013 ; Vol. 3.
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