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Title: Harnessing GLUT1-targeted pro-oxidant ascorbate for synergistic phototherapeutics
Authors: Koo, Seyoung
Lee, Min-Goo
Sharma, Amit
Li, Mingle
Zhang, Xingcai
Pu, Kanyi
Chi, Sung-Gil
Kim, Jong Seung
Keywords: Engineering::Bioengineering
Issue Date: 2022
Source: Koo, S., Lee, M., Sharma, A., Li, M., Zhang, X., Pu, K., Chi, S. & Kim, J. S. (2022). Harnessing GLUT1-targeted pro-oxidant ascorbate for synergistic phototherapeutics. Angewandte Chemie (International Ed. in English), 61(17), e202110832-.
Journal: Angewandte Chemie (International ed. in English)
Abstract: Despite extensive efforts to realize effective photodynamic therapy (PDT), there is still a lack of therapeutic approaches concisely structured to mitigate the major obstacles of PDT in clinical applications. Herein, we report a molecular strategy exploiting ascorbate chemistry to enhance the efficacy of PDT in cancer cells overexpressing glucose transporter 1 (GLUT1). AA-EtNBS, a 5-O-substituted ascorbate-photosensitizer (PS) conjugate, undergoes a reversible structural conversion of the ascorbate moiety in the presence of reactive oxygen species (ROS) and glutathione (GSH), thereby promoting its uptake in GLUT1-overexpressed KM12C colon cancer cells and perturbing tumor redox homeostasis, respectively. Due to the unique pro-oxidant role of ascorbate in tumor environments, AA-EtNBS effectively sensitized KM12C cancer cells prior to PS-mediated generation of superoxide radicals under near-infrared (NIR) illumination. AA-EtNBS successfully exhibited GLUT1-targeted synergistic therapeutic efficacy during PDT both in vitro and in vivo. Therefore, this study outlines a promising strategy employing ascorbate both as a targeting unit for GLUT1-overexpressed cancer cells and redox homeostasis destruction agent, thereby enhancing therapeutic responses towards anticancer treatment when used in conjunction with conventional PDT.
ISSN: 1433-7851
DOI: 10.1002/anie.202110832
Rights: © 2022 Wiley-VCH GmbH. All rights reserved.
Fulltext Permission: none
Fulltext Availability: No Fulltext
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