Fiche publication
Date publication
avril 2026
Journal
Journal of the American Chemical Society
Auteurs
Membres identifiés du Cancéropôle Est :
Dr FROCHOT Céline
Tous les auteurs :
Zhang Y, Xiao Z, Southwell JW, Gao R, Saubaméa B, Moinard M, Arnoux P, Frochot C, Mesdom P, Gasser G
Lien Pubmed
Résumé
Pyroptosis plays an emerging role in cancer immunotherapy, however, most currently known compounds that activate this cell death mechanism were discovered serendipitously. Here, we report a pyroptosis-inducing strategy that works through metabolic reprogramming of cancer cells to enhance antitumor immunity. Specifically, an osmium-based photosensitizer () was covalently attached to a small-molecule glutamine carrier protein inhibitor (IMD-0354), to construct the conjugate . This conjugate significantly enhanced the photosensitizer's uptake into cancer cells via the glutamine metabolic pathway, inhibited glutamine uptake, and promoted mitochondrial targeting. As a result, upon light irradiation, induced mitochondrial damage and impaired electron transport chain function as well as intracellular redox homeostasis, leading to a switch in the mode of cell death from the apoptosis typically observed with to gasdermin D (GSDMD)-mediated pyroptosis. Our study offers a new avenue for the development of scalable pyroptosis-inducing agents.
Référence
J Am Chem Soc. 2026 04 21;:
