Selective ablation of β-galactosidase-expressing cells with a rationally designed activatable photosensitizer

Yuki Ichikawa, Mako Kamiya, Fumiaki Obata, Masayuki Miura, Takuya Terai, Toru Komatsu, Tasuku Ueno, Kenjiro Hanaoka, Tetsuo Nagano, Yasuteru Urano

Research output: Contribution to journalArticlepeer-review

75 Citations (Scopus)

Abstract

We have developed an activatable photosensitizer capable of specifically inducing the death of β-galactosidase-expressing cells in response to photoirradiation. By using a selenium-substituted rhodol scaffold bearing β-galactoside as a targeting substituent, we designed and synthesized HMDESeR-βGal, which has a non-phototoxic spirocyclic structure owing to the presence of the galactoside moiety. However, β-galactosidase efficiently converted HMDESeR-βGal into phototoxic HMDESeR, which exists predominantly in the open xanthene form. This structural change resulted in drastic recovery of visible-wavelength absorption and the ability to generate singlet oxygen (1O2). When HMDESeR-βGal was applied to larval Drosophila melanogaster wing disks, which express β-galactosidase only in the posterior region, photoirradiation induced cell death in the β-galactosidase-expressing region with high specificity. Bull's eye! An activatable photosensitizer capable of specifically inducing the death of β-galactosidase-expressing cells in response to light irradiation was developed. Reaction with the enzyme resulted in a dynamic structural change to the phototoxic open form (see scheme), thus enabling the specific ablation of cells of interest in living tissues.

Original languageEnglish
Pages (from-to)6772-6775
Number of pages4
JournalAngewandte Chemie - International Edition
Volume53
Issue number26
DOIs
Publication statusPublished - 2014 Jun 23
Externally publishedYes

Keywords

  • activatable photosensitizers
  • cell ablation
  • fluorescent probes
  • intramolecular spirocyclization
  • selenium

ASJC Scopus subject areas

  • Catalysis
  • Chemistry(all)

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