Premium
An Ethacrynic Acid‐Brominated BODIPY Photosensitizer (EA‐BPS) Construct Enhances the Lethality of Reactive Oxygen Species in Hypoxic Tumor‐Targeted Photodynamic Therapy
Author(s) -
Won Miae,
Koo Seyoung,
Li Hao,
Sessler Jonathan L.,
Lee Jin Yong,
Sharma Amit,
Kim Jong Seung
Publication year - 2021
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.202012687
Subject(s) - photodynamic therapy , reactive oxygen species , photosensitizer , chemistry , glutathione , bodipy , in vivo , apoptosis , cytotoxicity , cancer research , pharmacology , in vitro , biochemistry , biophysics , medicine , enzyme , biology , photochemistry , fluorescence , microbiology and biotechnology , quantum mechanics , physics , organic chemistry
Despite being a clinically approved intervention for cancer, photodynamic therapy (PDT) still suffers from limitations. Prime among these is a therapeutic response that is mostly oxygen dependent. This limits the utility of PDT in treating hypoxic tumors since lower levels of cytotoxic reactive oxygen species (ROS) are generated in regions of low oxygen tension. Glutathione‐pi (GST‐pi) is a key enzyme that militates against ROS‐mediated apoptosis. We report herein a new construct, EA‐BPS, that contains both a brominated BODIPY photosensitizer (BPS) and an ethacrynic acid (EA) GST‐pi inhibitor. Photoirradiation of EA‐BPS induces a synergistic antitumor effect that results from the combination of ROS production and GST‐pi inhibition. Relative to BPS alone, an enhanced cell‐killing effect is seen under hypoxic conditions both in vitro and in vivo. We conclude that by making better use of the available oxygen in tumor environments, improved therapeutic PDT outcomes should be achievable even under hypoxic conditions.