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

Joël Daouk,Alain Delconte,Denise Béchet,Mathilde Iltis,Hervé Schohn,Paul Rocchi,Benoît Habermeyer,François Lux,Philippe Arnoux,Batoul Dhaini,Olivier Tillement,Muriel Barberi-Heyob,Céline Frochot

doi:10.3390/ph14050396

Abstract

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.

Highlights

We evaluated the effect of X-photodynamic therapy (PDT) on human GBM U-251 MG cell survival after taneously support a photodynamic effect
We already demonstrated that the grafting of P1 on AGuIX doped with Gd induced a hydrodynamic diameter at about 11.1 nm, twice as large as the original AGuIX@Gd nanoparticle, with an estimated diameter at 4.9 nm on average [38]
Gd in the original AGuIX@Gd by Tb and grafted P1 to demonstrate the interest of such nanoparticle in X-PDT

Summary

Introduction

Glioblastoma multiforme (GBM) is one of the main incurable brain tumors, mainly due to the presence of infiltrated cells within the parenchyma, responsible for GBM recurrence into the surrounding brain tissue [1]. Brain exposure to X-ray involves the generation of oxidative stress, which are responsible for DNA alteration, lipid peroxidation, protein oxidation, and cell redox statue changes, triggering cells to cell death [3]. These effects are not limited to malignant cells, and alter surrounding cells.

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Results

Conclusion