Terbium-Based AGuIX-Design Nanoparticle to Mediate X-ray-Induced Photodynamic Therapy.
Joël DaoukMathilde IltisBatoul DhainiDenise BéchetPhilippe ArnouxPaul RocchiAlain DelconteBenoît HabermeyerFrançois LuxCéline FrochotOlivier TillementMuriel Barberi-HeyobHervé SchohnPublished in: Pharmaceuticals (Basel, Switzerland) (2021)
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.
Keyphrases
- photodynamic therapy
- induced apoptosis
- cell cycle arrest
- energy transfer
- cell death
- quantum dots
- mycobacterium tuberculosis
- high resolution
- high glucose
- endothelial cells
- physical activity
- oxidative stress
- magnetic resonance imaging
- computed tomography
- endoplasmic reticulum stress
- drug induced
- radiation induced
- high throughput
- radiation therapy
- cell proliferation
- combination therapy
- iron oxide