Harnessing GLUT1-Targeted Pro-oxidant Ascorbate for Synergistic Phototherapeutics

Seyoung Koo, Min Goo Lee, Amit Sharma, Mingle Li, Xingcai Zhang, Kanyi Pu, Sung Gil Chi, Jong Seung Kim

Research output: Contribution to journalArticlepeer-review

15 Citations (Scopus)


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.

Original languageEnglish
Article numbere202110832
JournalAngewandte Chemie - International Edition
Issue number17
Publication statusPublished - 2022 Apr 19

Bibliographical note

Publisher Copyright:
© 2022 Wiley-VCH GmbH.


  • Ascorbate
  • GLUT1
  • Phototherapeutics
  • Pro-Oxidant
  • Targeted Therapy

ASJC Scopus subject areas

  • Catalysis
  • General Chemistry


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