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

Angew Chem Int Ed Engl. 2014 Jun 23;53(26):6772-5. doi: 10.1002/anie.201403221. Epub 2014 May 21.

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 ((1)O2). 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.

Keywords: activatable photosensitizers; cell ablation; fluorescent probes; intramolecular spirocyclization; selenium.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Drosophila melanogaster / growth & development
  • Fluorescent Dyes / chemistry
  • HEK293 Cells
  • Humans
  • Hydrogen-Ion Concentration
  • Larva / growth & development
  • Lasers
  • Photosensitizing Agents / chemistry
  • Photosensitizing Agents / toxicity
  • Selenium / chemistry
  • Selenium Compounds / chemistry*
  • Selenium Compounds / toxicity
  • Singlet Oxygen / metabolism
  • Thermodynamics
  • Wings, Animal / drug effects
  • Wings, Animal / growth & development
  • beta-Galactosidase / chemistry
  • beta-Galactosidase / metabolism*

Substances

  • Fluorescent Dyes
  • HMDESeR
  • Photosensitizing Agents
  • Selenium Compounds
  • Singlet Oxygen
  • beta-Galactosidase
  • Selenium