Added Value of Scintillating Element in Cerenkov-Induced Photodynamic Therapy.
Perrine SchnellerCharlotte ColletQuentin BeenPaul RocchiFrançois LuxOlivier TillementMuriel Barberi-HeyobHervé SchohnJoël DaoukPublished in: Pharmaceuticals (Basel, Switzerland) (2023)
Cerenkov-induced photodynamic therapy (CR-PDT) with the use of Gallium-68 ( 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 68 Ga positrons is involved in nanoscintillator and photosensitizer activation, the cytotoxic effect obtained by PDT remains controversial. Herein, we tested whether free 68 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 68 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 68 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 68 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.
Keyphrases
- photodynamic therapy
- pet ct
- mycobacterium tuberculosis
- energy transfer
- fluorescence imaging
- high glucose
- monte carlo
- induced apoptosis
- diabetic rats
- endothelial cells
- quantum dots
- oxidative stress
- cell cycle arrest
- high throughput
- drug induced
- bone marrow
- living cells
- radiation therapy
- cell death
- cell therapy
- magnetic resonance imaging
- mesenchymal stem cells
- dual energy
- induced pluripotent stem cells
- pi k akt