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Article Dans Une Revue Photodiagnosis and Photodynamic Therapy Année : 2023

Using rare-earth based nanoscintillators for X-ray induced photodynamic therapy

Fréderic Chaput
Christine Moriscot
Benoît Gallet

Résumé

Pancreatic cancer is associated with a poor prognosis despite multimodal treatments consisting in surgery, chemotherapy and radiotherapy. Photodynamic therapy (PDT) is a promising treatment that aims to activate photosensitizers with light in order to induce local cell damage. However, its use for treating deep tumors, including pancreatic tumors, is limited because of the low penetration depth of light in tissues. To overcome this limitation, it has been proposed to use nanoscintillators (NS) that down-convert ionizing radiation such as X-rays used in radiotherapy, into UV-visible photons. These nanoparticles could improve the efficacy of radiotherapy through at least three effects: the radiation dose-enhancement effect1 that is a physical effect due to the accumulation of heavy elements in the vicinity of tumors, the emission of UV-C photons that increase direct DNA damage, and the activation of photodynamic therapy by X-rays (X-PDT)2. The aim of our project is to conjugate NS with appropriate photosensitizers to achieve PDT during radiotherapy. Here, we present our results obtained with lanthanum fluoride nanoscintillators doped with cerium (LaF3:Ce) coated with either triphosphate or polyethylene glycol (PEG). The choice of the coating is of major importance because it could modify the NS toxicity and uptake in cells and microtumors, and thus impact their therapeutic efficacy. We studied the properties of NS on both 2D and 3D culture models of pancreatic tumors, grown in suspension or as adherent microtumors. As LaF3:Ce nanoparticles are only excited by UV photons, they could not be observed with a conventional confocal microscope. Therefore, we used X-ray fluorescence microscopy (ID16, ESRF) and transmission electron microscopy (IBS) to analyze their distribution within the cells, and X-ray fluorescence microtomography (P06, DESY) to study their accumulation in tumor spheroids. We observed that NS functionalized with triphosphate coating formed many aggregates and were present in greater amounts within the cells, compared to those with PEG coating. These experiments also showed a higher concentration of lanthanum – the main constituent of NS – inside the tumor spheroids when a triphosphate coating was used. We obtained similar intrinsic toxicities for both coatings, and promising preliminary results regarding the therapeutic potential of LaF3:Ce NS. We are currently investigating the role of the NS coating on treatment efficacy, biodistribution and pharmacokinetics using in vivo models of pancreatic tumors. Finally, their conjugation with photosensitizers will be investigated to evaluate X-PDT efficacy.

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Chimie
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Dates et versions

hal-04293863 , version 1 (19-11-2023)

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Paternité - Pas d'utilisation commerciale - Pas de modification

Identifiants

Citer

Clémentine Fulbert, Sarah Stelse-Masson, Fréderic Chaput, Thibault Jacquet, Anthony Nomezine, et al.. Using rare-earth based nanoscintillators for X-ray induced photodynamic therapy. Photodiagnosis and Photodynamic Therapy, 2023, 41 (10), pp.103421. ⟨10.1016/j.pdpdt.2023.103421⟩. ⟨hal-04293863⟩
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