Thèse
Publié le 18 février 2019 | Mis à jour le 6 janvier 2020

Delphine VERNOS-BRICHART 2019-2021 - PhD director: Claire Rodriguez-Lafrasse, co-director: Olivier Tillement

équipes IPNL-LRCM, ILM-FENNEC

Titre: Novel generation of ultrasmall high Z tailored nanoparticles for tumor cell radiosensitization

One of the greatest challenges of radiotherapy is to concentrate the effect of radiation on cancer cells while sparing the healthy surrounding tissues. Gadolinium-based nanoparticles (AGuIX®) have proven their radio-sensitizing efficiency in different tumor models, both in vitro and in vivo. These results led to two ongoing clinical trials. In this context, it is important to consolidate the medical development and to develop the next optimized generation of ultrasmall nanoparticles for diagnostic and therapy. To do so, we decided to synthesize nanoparticles containing atoms with high-atomic number. Gadolinium atoms can provide radiation dose amplification. However, the probability for photoelectric interaction with a given atom is proportionate to Z3, where Z is the atomic number of the atom. Therefore, gadolinium (ZGd = 64) has a much lower probability of interaction than bismuth (ZBi = 83) and both have a much higher probability of interaction than Yttrium (ZY = 39).
The aim of the thesis is to (i) study the radiosensitizing effect of bismuth nanoparticles in different cellular models and (ii) establish a relation between the atomic number of the metal present in the nanoparticle and the radio-enhancing effect.
To this end, a novel synthesis process led to ultrasmall nanoparticles made of polysiloxane displaying free chelates on their surface. This versatile synthesis permits the addition of selected metals (gadolinium, bismuth or yttrium) at the surface of the nanoparticles. To assess the radiosensitizing effect of these nanoparticles, different cell lines were irradiated with photons (220 kV) and the cell response was measured with clonogenic survival assays and other biological endpoints.

  • Éditeur
    Thèse en cours depuis le 1er janvier 2019
  • Auteur(s)
    Delphine Vernos