한빛사 논문
Seyoung Koo+, Min-Goo Lee+, Amit Sharma, Mingle Li, Xingcai Zhang, Kanyi Pu,* Sung-Gil Chi,* and Jong Seung Kim*
[*] Dr. S. Koo,+ Dr. M. Li, Prof. J. S. Kim
Department of Chemistry, Korea University Seoul 02841 (Korea)
Dr. M.-G. Lee,+ Prof. S.-G. Chi
Department of Life Science, Korea University Seoul 02841 (Korea)
Prof. A. Sharma
Central Scientific Instruments Organisation (CSIR) Sector-30C, Chandigarh 160030 (India)
Dr. X. Zhang
John A. Paulson School of Engineering and Applied Sciences Harvard University Cambridge, MA 02138 (USA)
Dr. X. Zhang
School of Engineering, Massachusetts Institute of Technology Cambridge, MA 02139 (USA)
Prof. K. Pu
School of Chemical and Biomedical Engineering Nanyang Technological University 70 Nanyang Drive, 637457 Singapore (Singapore)
[+] These authors contributed equally to this work.
*Corresponding author.
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.
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