Y2O3 Nanoparticles and X-ray Radiation-Induced Effects in Melanoma Cells.

Ioana Porosnicu,Bogdan I Bita,Cristian V A Munteanu,Felix Sima,Octavian G Duliu,Cristian M Butnaru,Ion Tiseanu,Elena Stancu

doi:10.3390/molecules26113403

Abstract

The innovative strategy of using nanoparticles in radiotherapy has become an exciting topic due to the possibility of simultaneously improving local efficiency of radiation in tumors and real-time monitoring of the delivered doses. Yttrium oxide (Y2O3) nanoparticles (NPs) are used in material science to prepare phosphors for various applications including X-ray induced photodynamic therapy and in situ nano-dosimetry, but few available reports only addressed the effect induced in cells by combined exposure to different doses of superficial X-ray radiation and nanoparticles. Herein, we analyzed changes induced in melanoma cells by exposure to different doses of X-ray radiation and various concentrations of Y2O3 NPs. By evaluation of cell mitochondrial activity and production of intracellular reactive oxygen species (ROS), we estimated that 2, 4, and 6 Gy X-ray radiation doses are visibly altering the cells by inducing ROS production with increasing the dose while at 6 Gy the mitochondrial activity is also affected. Separately, high-concentrated solutions of 25, 50, and 100 µg/mL Y2O3 NPs were also found to affect the cells by inducing ROS production with the increase of concentration. Additionally, the colony-forming units assay evidenced a rather synergic effect of NPs and radiation. By adding the NPs to cells before irradiation, a decrease of the number of proliferating cell colonies was observed with increase of X-ray dose. DNA damage was evidenced by quantifying the γ-H2AX foci for cells treated with Y2O3 NPs and exposed to superficial X-ray radiation. Proteomic profile confirmed that a combined effect of 50 µg/mL Y2O3 NPs and 6 Gy X-ray dose induced mitochondria alterations and DNA changes in melanoma cells.

Highlights

Rare earth oxide nanoparticles (NPs) have gained extensive attention over the last years due to their potential as nanodrugs for various biomedical applications including in vitro cancer cell imaging, in vivo tumor imaging through active targeting, X-ray imaging, photodynamic therapy etc. [1,2]
Chuang et al showed that Y2O3:Eu covered by silica shell (Y2O3: Eu@SiO2) NPs act as independent photosensitizers for X-ray induced photodynamic therapy by generating an increased amount of reactive oxygen species (ROS) under X-ray irradiation that lead to cancer cell death [10]
We have evaluated the effect of Y2O3 NPs under X-ray irradiation on A375 melanoma cells

Summary

Introduction

Rare earth oxide nanoparticles (NPs) have gained extensive attention over the last years due to their potential as nanodrugs for various biomedical applications including in vitro cancer cell imaging, in vivo tumor imaging through active targeting, X-ray imaging, photodynamic therapy etc. [1,2]. Europium (Eu) doped Y2O3 has been intensively studied as scintillator for medical imaging, radiation detection and dosimetry [3,4,5,6,7]. Chuang et al showed that Y2O3:Eu covered by silica shell (Y2O3: Eu@SiO2) NPs act as independent photosensitizers for X-ray induced photodynamic therapy by generating an increased amount of reactive oxygen species (ROS) under X-ray irradiation that lead to cancer cell death [10]. This was the confirmation that Y2O3-based NPs may directly induce X-ray photodynamic effects without the presence of conventional photosensitizers

Methods

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Discussion

Conclusion