Terbium-Based AGuIX-Design Nanoparticle to Mediate X-ray-Induced Photodynamic Therapy.

Fiche publication

Date publication

avril 2021

Journal

Pharmaceuticals (Basel, Switzerland)

Auteurs

Membres identifiés du Cancéropôle Est :
Pr BARBERI-HEYOB Muriel , Dr FROCHOT Céline , Pr SCHOHN Hervé , Dr DAOUK Joël

Tous les auteurs :
Daouk J, Iltis M, Dhaini B, Béchet D, Arnoux P, Rocchi P, Delconte A, Habermeyer B, Lux F, Frochot C, Tillement O, Barberi-Heyob M, Schohn H

Lien Pubmed

https://www.ncbi.nlm.nih.gov/pubmed/33922073

Résumé

X-ray-induced photodynamic therapy is based on the energy transfer from a nanoscintillator to a photosensitizer molecule, whose activation leads to singlet oxygen and radical species generation, triggering cancer cells to cell death. Herein, we synthesized ultra-small nanoparticle chelated with Terbium (Tb) as a nanoscintillator and 5-(4-carboxyphenyl succinimide ester)-10,15,20-triphenyl porphyrin (P1) as a photosensitizer (AGuIX@Tb-P1). The synthesis was based on the AGuIX@ platform design. AGuIX@Tb-P1 was characterised for its photo-physical and physico-chemical properties. The effect of the nanoparticles was studied using human glioblastoma U-251 MG cells and was compared to treatment with AGuIX@ nanoparticles doped with Gadolinium (Gd) and P1 (AguIX@Gd-P1). We demonstrated that the AGuIX@Tb-P1 design was consistent with X-ray photon energy transfer from Terbium to P1. Both nanoparticles had similar dark cytotoxicity and they were absorbed in a similar rate within the cells. Pre-treated cells exposure to X-rays was related to reactive species production. Using clonogenic assays, establishment of survival curves allowed discrimination of the impact of radiation treatment from X-ray-induced photodynamic effect. We showed that cell growth arrest was increased (35%-increase) when cells were treated with AGuIX@Tb-P1 compared to the nanoparticle doped with Gd.