An Activatable Photosensitizer Targeted to γ-Glutamyltranspeptidase

Mayumi Chiba, Yuki Ichikawa, Mako Kamiya, Toru Komatsu, Tasuku Ueno, Kenjiro Hanaoka, Tetsuo Nagano, Norbert Lange, Yasuteru Urano

Research output: Contribution to journalArticlepeer-review

78 Citations (Scopus)

Abstract

We adopted a spirocyclization-based strategy to design γ-glutamyl hydroxymethyl selenorhodamine green (gGlu-HMSeR) as a photo-inactive compound that would be specifically cleaved by the tumor-associated enzyme γ-glutamyltranspeptidase (GGT) to generate the potent photosensitizer HMSeR. gGlu-HMSeR has a spirocyclic structure and is colorless and does not show marked phototoxicity toward low-GGT-expressing cells or normal tissues upon irradiation with visible light. In contrast, HMSeR predominantly takes an open structure, is colored, and generates reactive oxygen species upon irradiation. The γ-glutamyl group thus serves as a tumor-targeting moiety for photodynamic therapy (PDT), switching on tumor-cell-specific phototoxicity. To validate this system, we employed chick chorioallantoic membrane (CAM), a widely used model for preliminary evaluation of drug toxicity. Photoirradiation after gGlu-HMSeR treatment resulted in selective ablation of implanted tumor spheroids without damage to healthy tissue.

Original languageEnglish
Pages (from-to)10418-10422
Number of pages5
JournalAngewandte Chemie - International Edition
Volume56
Issue number35
DOIs
Publication statusPublished - 2017 Aug 21
Externally publishedYes

Keywords

  • photodynamic therapy
  • photosensitizers
  • rhodamines
  • targeted antitumor agents
  • γ-glutamyl transpeptidase

ASJC Scopus subject areas

  • Catalysis
  • Chemistry(all)

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