SCINTILLATING NANOPARTICLES FOR X-RAYACTIVATED PHOTODYNAMIC THERAPY AND NEXT-GENERATION IN VIVO DOSIMETRY

Abstract

Objective: The aim of this study was to develop scintillating nanoparticles to simultaneously monitor the x-ray dose delivered to tumors during treatments with x-ray-activated photodynamic therapy (X-PDT). Methods: A microfluidic synthesis was developed to grow GdF3:Eu theranostic scintillating nanoparticles (ScNPs). The flow reaction was optimized
to enhance scintillation emission from the Eu+3 ions. Results: The as-prepared ~15 nm rhombohedral-shaped nanoparticles self-assembled into ~100 nm mesoporous flower-like nanostructures, but the rhombohedral units remained intact
and the scintillation spectra were unaltered. The conjugation of the ScNPs with multilayers of methylene blue (MB) in a
core-shell structure (GdF@MB) resulted in enhanced singlet oxygen (1O2
) generation under x-ray irradiation, with maximum 1O2
production for nanoparticles with 4 MB layers (GdF@4MB). High 1O2
yield was further evidenced in cytotoxicity
assays, demonstrating complete cell death only for the association of ScNPs with MB and x-rays. Because the scintillating
Eu+3 emission at 694 nm was within the therapeutic window and was only partially absorbed by the MB molecules, it
was explored for getting in vivo dosimetric information. Using porcine skin and fat to simulate the optical and radiological properties of human tissues, we showed that the scintillation light can be detected for a tissue layer of ~16 mm, thick
enough to be employed in radiotherapy treatments of breast cancers, for instance. Conclusion: The GdF3:Eu ScNPs and
the GdF@4MB nanoconjugates are strong candidates for treating cancer with X-PDT while monitoring the treatment and
the radiation dose delivered, opening new avenues to develop a next-generation modality of real-time in vivo dosimetry.