한빛사 논문
Miae Won+, Seyoung Koo+, Hao Li+, Jonathan L. Sessler,* Jin Yong Lee,* Amit Sharma,* and Jong Seung Kim*
[*] Dr. M. Won,[+] Dr. S. Koo,[+] Prof. J. S. Kim
Department of Chemistry, Korea University
Seoul 02841 (Korea)
H. Li,[+] Prof. J. Y. Lee
Department of Chemistry, Sungkyunkwan University
Suwon 16419 (Korea)
Prof. J. L. Sessler
Department of Chemistry, University of Texas at Austin
Austin, TX 78712-1224 (USA)
Dr. A. Sharma
CSIR—Central Scientific Instruments Organisation, Sector-30 C
Chandigarh 160030 (India)
[+] These authors contributed equally to this work.
*Corresponding author
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.
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