4.8 Article

Harnessing GLUT1-Targeted Pro-oxidant Ascorbate for Synergistic Phototherapeutics

期刊

出版社

WILEY-V C H VERLAG GMBH
DOI: 10.1002/anie.202110832

关键词

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

资金

  1. National Research Foundation of Korea [2018R1A3B1052702, NRF-2021R1A2B03002487, NRF-2018R1D1A1B07041512, 2020H1D3A1A02080172]
  2. Basic Science Research Program [2020R1A6A3A01100558]
  3. 2018 Korea University Research Fellow Grant
  4. Department of Biotechnology, New Delhi [BT/RLF/Re-entry/59/2018]
  5. National Research Foundation of Korea [2020H1D3A1A02080172] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)

向作者/读者索取更多资源

This study presents a molecular strategy that enhances the efficacy of photodynamic therapy (PDT) by utilizing ascorbate chemistry. The strategy targets cancer cells overexpressing glucose transporter 1 (GLUT1) and disrupts tumor redox homeostasis, leading to improved therapeutic responses. The approach shows promising synergistic effects in vitro and in vivo.
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.

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