Lanthanides-Based Nanoparticles Conjugated with Rose Bengal for FRET-Mediated X-Ray-Induced PDT

Batoul Dhaini; Joël Daouk; Hervé Schohn; Philippe Arnoux; Valérie Jouan-Hureaux; Albert Moussaron; Agnès Hagege; Mathilde Achard; Samir Acherar; Tayssir Hamieh; Céline Frochot

arXiv · 2511.10116

Lanthanides-Based Nanoparticles Conjugated with Rose Bengal for FRET-Mediated X-Ray-Induced PDT

Batoul Dhaini·Joël Daouk·Hervé Schohn·Philippe Arnoux·Valérie Jouan-Hureaux·Albert Moussaron·Agnès Hagege·Mathilde Achard·Samir Acherar·Tayssir Hamieh·Céline Frochot

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Abstract

In order to find a good candidate for F{ö}rster Resonance Energy Transfer (FRET)-mediated X-ray-induced photodynamic therapy (X-PDT) for the treatment of cancer, lanthanide (Ln)-based AGuIX nanoparticles (NPs) conjugated with Rose Bengal (RB) as a photosensitizer (PS) were synthesized. X-PDT overcomes the problem of the poor penetration of visible light into tissues, which limits the efficacy of PDT in the treatment of deep-seated tumors. It is essential to optimize FRET efficiency by maximizing the overlap integral between donor emission and acceptor absorption and lengthening the duration of the donor emission. In this study, we optimized energy transfer between a scintillator (Sc) as a donor and a PS as an acceptor. Terbium (Tb) and Gadolinium (Gd) as Scs and Rose RB as a PS were chosen. The study of energy transfer between Tb, Gd and RB in solution and chelated on AGuIX NPs proved to be FRET-like. RB was conjugated directly onto AGuIX NPs (i.e., AGuIX Ln@RB), and the use of a spacer arm (i.e., AGuIX Ln@spacer arm-RB) increased FRET efficiency. Singlet oxygen production by these NPs was observed under UV--visible illumination and X-ray irradiation. The in vitro bioassay demonstrated 52% cell death of U-251MG derived from human malignant glioblastoma multiforme at a concentration of 1 $μ$M RB after illumination and irradiation (2 Gy, 320 kV, 10 mA, 3 Gy/min at 47 cm). In addition, the RB-coupled NRP-1-targeting peptide (i.e., K(RB)DKPPR) was conjugated onto AGuIX NPs by a thiol-maleimide click chemistry reaction, and an affinity in the nM range was observed.

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Batoul Dhaini, Joël Daouk, Hervé Schohn, Philippe Arnoux, Valérie Jouan-Hureaux, Albert Moussaron, Agnès Hagege, Mathilde Achard, Samir Acherar, Tayssir Hamieh, Céline Frochot. 2025-11-13. Lanthanides-Based Nanoparticles Conjugated with Rose Bengal for FRET-Mediated X-Ray-Induced PDT. https://arxiv.org/abs/2511.10116

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