An Ethacrynic Acid-Brominated BODIPY Photosensitizer (EA-BPS) Construct Enhances the Lethality of Reactive Oxygen Species in Hypoxic Tumor-Targeted Photodynamic Therapy

Miae Won, Seyoung Koo, Hao Li, Jonathan L. Sessler, Jin Yong Lee, Amit Sharma, Jong Seung Kim

Research output: Contribution to journalArticlepeer-review

10 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)3196-3204
Number of pages9
JournalAngewandte Chemie - International Edition
Volume60
Issue number6
DOIs
Publication statusPublished - 2021 Feb 8

Keywords

  • BODIPY
  • Hypoxia
  • ethacrynic acid
  • glutathione S-transferase-pi
  • photodynamic therapy

ASJC Scopus subject areas

  • Catalysis
  • Chemistry(all)

Fingerprint

Dive into the research topics of 'An Ethacrynic Acid-Brominated BODIPY Photosensitizer (EA-BPS) Construct Enhances the Lethality of Reactive Oxygen Species in Hypoxic Tumor-Targeted Photodynamic Therapy'. Together they form a unique fingerprint.

Cite this