Monte Carlo simulations guided by imaging to predict the in vitro ranking of radiosensitizing nanoparticles

Paul Retif,1–3 Aurélie Reinhard,2,3 Héna Paquot,2,3 Valérie Jouan-Hureaux,2,3 Alicia Chateau,2,3 Lucie Sancey,4 Muriel Barberi-Heyob,2,3 Sophie Pinel,2,3 Thierry Bastogne2,3,5 1Unité de Physique Médicale, CHR Metz-Thionville, Ars-Laquenexy, 2Université de Lorraine, 3CRAN, UMR 7039, CNRS, Vandoeuvre-lès-Nancy, 4Institut Lumière Matière, UMR 5306, CNRS, Villeurbanne, 5INRIA-BIGS & CRAN, Université de Lorraine, Vandoeuvre-lès-Nancy Cedex, France Abstract: This article addresses the in silico–in vitro prediction issue of organometallic nanoparticles (NPs)-based radiosensitization enhancement. The goal was to carry out computational experiments to quickly identify efficient nanostructures and then to preferentially select the most promising ones for the subsequent in vivo studies. To this aim, this interdisciplinary article introduces a new theoretical Monte Carlo computational ranking method and tests it using 3 different organometallic NPs in terms of size and composition. While the ranking predicted in a classical theoretical scenario did not fit the reference results at all, in contrast, we showed for the first time how our accelerated in silico virtual screening method, based on basic in vitro experimental data (which takes into account the NPs cell biodistribution), was able to predict a relevant ranking in accordance with in vitro clonogenic efficiency. This corroborates the pertinence of such a prior ranking method that could speed up the preclinical development of NPs in radiation therapy. Keywords: biomedical applications of radiations, computer simulation, nanomedicine, virtual screenin

Rose Bengal coupled to AGuIX NPs for anti-cancer photodynamic therapy

Rose Bengal is a well-known photosensitizer used in the treatment of several diseases [1, 2]. This photosensitizer produces a large amount of singlet oxygen upon specific illumination, which allows its use in pho-todynamic therapy [3]. The work to be presented highlights the passive tumor targeting by coupling Rose Bengal to nanoparticles in clinical phase 2 AGuIX chelated with lanthanides (Terbium or Gadolinium). One of the limitations of photodynamic therapy is the poor penetration of light into the tissues [4]. X-ray excitation of AGuIX(Ln)@RB over-comes this problem. Following the excitation of the lanthanide by X-ray, a FRET energy transfer from lanthanide to Rose Bengal takes place. Rose Bengal is then able to produce singlet oxygen. To enhance the tar-geting, peptide can be covalently couple to the nanoparticles [5]. Two types of peptide targeting NRP1 receptors over-expressed in neovessels were grafted on the nanoparticles.This presentation focuses on the synthesis, photophysical properties of these nanoparticles, physical characterization, the type of energy trans-fer between the species, and the in vitro PDT-X effect