Fiche publication
Date publication
janvier 2023
Journal
Pharmaceuticals (Basel, Switzerland)
Auteurs
Membres identifiés du Cancéropôle Est :
Pr BARBERI-HEYOB Muriel
,
Pr SCHOHN Hervé
,
Dr DAOUK Joël
Tous les auteurs :
Schneller P, Collet C, Been Q, Rocchi P, Lux F, Tillement O, Barberi-Heyob M, Schohn H, Daouk J
Lien Pubmed
Résumé
Cerenkov-induced photodynamic therapy (CR-PDT) with the use of Gallium-68 (Ga) as an unsealed radioactive source has been proposed as an alternative strategy to X-ray-induced photodynamic therapy (X-PDT). This new strategy still aims to produce a photodynamic effect with the use of nanoparticles, namely, AGuIX. Recently, we replaced Gd from the AGuIX@ platform with Terbium (Tb) as a nanoscintillator and added 5-(4-carboxyphenyl succinimide ester)-10,15,20-triphenylporphyrin (P1) as a photosensitizer (referred to as AGuIX@Tb-P1). Although Cerenkov luminescence from Ga positrons is involved in nanoscintillator and photosensitizer activation, the cytotoxic effect obtained by PDT remains controversial. Herein, we tested whether free Ga could substitute X-rays of X-PDT to obtain a cytotoxic phototherapeutic effect. Results were compared with those obtained with AGuIX@Gd-P1 nanoparticles. We showed, by Monte Carlo simulations, the contribution of Tb scintillation in P1 activation by an energy transfer between Tb and P1 after Cerenkov radiation, compared to the Gd-based nanoparticles. We confirmed the involvement of the type II PDT reaction during Ga-mediated Cerenkov luminescence, id est, the transfer of photon to AGuIX@Tb-P1 which, in turn, generated P1-mediated singlet oxygen. The effect of Ga on cell survival was studied by clonogenic assays using human glioblastoma U-251 MG cells. Exposure of pre-treated cells with AGuIX@Tb-P1 to Ga resulted in the decrease in cell clone formation, unlike AGuIX@Gd-P1. We conclude that CR-PDT could be an alternative of X-PDT.
Mots clés
AGuIX, Cerenkov radiation, Gadolinium, Monte Carlo simulations, Terbium, glioblastoma, photodynamic therapy, singlet oxygen
Référence
Pharmaceuticals (Basel). 2023 01 18;16(2):
