Lysosomes targeting pH activable imaging-guided photodynamic agents.
Fiche publication
Date publication
février 2023
Journal
Chembiochem : a European journal of chemical biology
Auteurs
Membres identifiés du Cancéropôle Est :
Dr ELHABIRI Mourad, Dr FIGLIOLA Carlotta, Pr DIDIER Pascal, Dr ANTON Halina
Tous les auteurs :
Figliola C, Anton H, Sutter C, Chériaux C, Sutter A, Mazan V, Elhabiri M, Didier P, Jacquemin D, Ulrich G
Lien Pubmed
Résumé
Photodynamic therapy (PDT) is a photochemistry-based medical treatment combining light at a specific wavelength and a photosensitizer (PS) in the presence of oxygen. Application of PDT as a conventional treatment is limited and clearly the approval in clinics of new PS is challenging. The selective accumulation of the PS in the targeted malignant cells is of paramount importance to reduce the side effects that are typical of the current worldwide approved PS. Here we report a new series of aniline- and iodine-substituted BODIPY derivatives (1-3) as promising lysosome-targeting and pH-responsive theranostic PS, which displayed a significant in vitro light-induced cytotoxicity, efficient imaging properties and low dark toxicity (for 2 and 3). These compounds were obtained in few reproducible synthetic steps and good yields. Spectroscopic and electrochemical measurements along with computational calculations confirmed the quenching of the emissive properties of the PS, while both fluorescence and 1O2 emission were obtained only under acidic conditions inducing amine protonation. The pKa values and pH-dependent emissive properties of 1-3 being established, their cellular uptake and activation in the lysosomal vesicles (pH ≈ 4-5) were confirmed by their co-localization with the commercial LysoTracker deep red and light-induced cytotoxicity (IC50 between 0.16 and 0.06 µM) against HeLa cancer cells.
Mots clés
photodynamic therapy, BODIPYs, intraorganellar activation, pH-responsive photosensitizers, selectivity
Référence
Chembiochem. 2023 02 23;:e202300139