Harnessing GLUT1-Targeted Pro-oxidant Ascorbate for Synergistic Phototherapeutics.
Angew Chem Int Ed Engl
; 61(17): e202110832, 2022 04 19.
Article
em En
| MEDLINE
| ID: mdl-35142018
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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Bases de dados:
MEDLINE
Assunto principal:
Fotoquimioterapia
/
Neoplasias
Limite:
Humans
Idioma:
En
Revista:
Angew Chem Int Ed Engl
Ano de publicação:
2022
Tipo de documento:
Article