Nanotoxicological study of downconversion Y₂O₃:Eu³⁺luminescent nanoparticles functionalized with folic acid for cancer cells bioimaging

Abstract

Luminescent lanthanide downconversion nanoparticles (DCNPs) provide a combination of high luminescence intensity, sharp emission peaks with narrow bandwidth and a large Stokes' shift, leading to high‐performance biomedical applications mainly for imaging. The purpose of this study is to present a nanotoxicological study of DCNPs Y2O3 codoped with Eu3+ and functionalized with folic acid (FA). These assessments include cytotoxicity, genotoxicity, hemocompatibility, and in vitro inflammatory studies. We demonstrated by flow cytometry and confocal microscope the internalization of FA‐DCNPs in breast cancer and melanoma cells. They were synthesized by sol–gel method and coated with a thin silica shell to make them biocompatible; also they were functionalized with amino groups and FA ligands that bind to the folate receptors (FR) located on the surface of the cancer cells studied. This functionalization enables the DCNPs to be internalized into the cancer cells via endocytosis by the conjugation FA‐FR. The DCNPs were characterized with transmission electron microscope, Fourier transform infrared spectroscopy and photoluminescence. The nanotoxicological assessments demonstrated that both nanoparticles (bare and functionalized) are no cytotoxic and no genotoxic at the tested concentrations (0.01–20 μg/mL) in three cell lines (breast, skin cancer, and osteoblasts). Also they are hemocompatible and do not exert nitric oxide production in vitro by macrophages. The FA‐DCNPs were clearly localized into the cell cytoplasm with bright red luminescence. Thus, herein we present a complete nanotoxicological study of FA‐DCNPs Y2O3 codoped with Eu3+ and we conclude that these nanoparticles are biocompatible and can be further used for cancer cells bioimaging.

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

“…The main objective of the study was to systematically analyze the biological effects on A375 cells induced by either Y 2 O 3 NPs or superficial X-ray radiation to eventually reveal the potential role of Y 2 O 3 NPs during X-ray exposure. We believe these investigations are essential for biomedical cancer applications in the new field of theranostics where Y 2 O 3 NPs could be used as intracellular dosimetric sensors during X-ray treatment via bioimaging of tumors [ 24 , 25 , 26 , 27 ].…”

Nanotoxicological Assessments to Warranty the use of Functionalized Y2O3 Nanoparticles for Biomedical Applications

“…FTIR analysis of bare and doped NPs was previously reported [34]. The PL of excitation and emission spectra of NPs and Y2O3:Eu 3+ (4% mol) bare and functionalized DCNPs-FA are depicted in Fig.…”

“…To probe the bio-and hemocompatibility of DCNPs we used fibroblasts cells (L929), and erythrocytes from peripheral blood samples, and we tested the in vitro inflammatory responses on macrophages (RAW 264.7). We previously reported a nanotoxicological study of Y2O3: Eu 3 (5% mol) DCNPs with MDA-MB-231, B16-F10 and RAW 264.7 cell lines [34], herein we present broader comparison of the Y2O3-based DCNPs for biomedical applications.…”

Hybrid AuNPs-3MPS-MTX nanosystem and its evaluation for treating cervical cancer and melanoma

“…The internalization of nanoparticles was evaluated by comparing the side scatter values of cell samples, as previously documented. 21 We seeded a density of 4 × 10 5 cells in a 12-well plate and cultured them for 24 hours at 37 °C with 5% CO 2 . Subsequently, the cells were washed with PBS and incubated with AuNPs-3MPS, AuNPs-3MPS-MTX and MTX at a concentration of 1 to 64 μg m −1 for 48 hours under the same conditions.…”