4.6 Article

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

Journal

PHARMACEUTICALS
Volume 14, Issue 5, Pages -

Publisher

MDPI
DOI: 10.3390/ph14050396

Keywords

glioblastoma multiforme; AGuIX (R); terbium; gadolinium; photodynamic therapy; X-ray-induced photodynamic therapy; singlet oxygen

Funding

  1. CRAN
  2. French Ligue Nationale Contre le Cancer
  3. European EURONANOMED II programme [447/15/GM]
  4. CPER IT2MP
  5. Laura: les couleurs de la vie association

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X-ray-induced photodynamic therapy based on nanoparticles with Terbium as a nanoscintillator and P1 as a photosensitizer showed promising results in treating human glioblastoma cells. Energy transfer from Terbium to P1 was consistent, leading to increased cell growth arrest compared to nanoparticles doped with Gadolinium.
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.

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