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.

中文翻译：

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用于癌细胞生物成像的叶酸功能化下转换 Y2O3:Eu3+ 发光纳米粒子的纳米毒理学研究。

发光镧系元素下转换纳米粒子 (DCNP) 提供了高发光强度、窄带宽和大斯托克斯位移的尖锐发射峰的组合，导致主要用于成像的高性能生物医学应用。本研究的目的是对与 Eu ³⁺共掺杂的 DCNPs Y ₂ O ₃进行纳米毒理学研究。并用叶酸 (FA) 进行功能化。这些评估包括细胞毒性、基因毒性、血液相容性和体外炎症研究。我们通过流式细胞术和共聚焦显微镜证明了 FA-DCNPs 在乳腺癌和黑色素瘤细胞中的内化。它们是通过溶胶-凝胶法合成的，并涂有一层薄薄的二氧化硅壳，使其具有生物相容性；此外，它们还被氨基和 FA 配体官能化，这些配体与位于所研究癌细胞表面的叶酸受体 (FR) 结合。这种功能化使 DCNP 能够通过结合 FA-FR 的内吞作用被内吞到癌细胞中。DCNPs 用透射电子显微镜、傅里叶变换红外光谱和光致发光表征。纳米毒理学评估表明，在三种细胞系（乳腺癌、皮肤癌和成骨细胞）中，两种纳米颗粒（裸露的和功能化的）在测试浓度（0.01-20 μg/mL）下均无细胞毒性和基因毒性。它们也是血液相容的，不会产生一氧化氮体外通过巨噬细胞。FA-DCNPs 清楚地定位在细胞质中，发出亮红色的光。因此，在本文中，我们对与 Eu ³⁺共掺杂的 FA-DCNPs Y ₂ O _{3 进行}了完整的纳米毒理学研究，我们得出结论，这些纳米颗粒具有生物相容性，可进一步用于癌细胞生物成像。