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An Activatable Photosensitizer Targeted to γ‐Glutamyltranspeptidase
Author(s) -
Chiba Mayumi,
Ichikawa Yuki,
Kamiya Mako,
Komatsu Toru,
Ueno Tasuku,
Hanaoka Kenjiro,
Nagano Tetsuo,
Lange Norbert,
Urano Yasuteru
Publication year - 2017
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201704793
Subject(s) - phototoxicity , photosensitizer , photodynamic therapy , chemistry , moiety , biophysics , reactive oxygen species , cytotoxicity , cancer research , biochemistry , stereochemistry , in vitro , photochemistry , biology , organic chemistry
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.