School of Engineering, Centro de Enseñanza Técnica y Superior (CETYS), Ensenada, Mexico.
Bionanotechnology Department, Centro de Nanociencias y Nanotecnología, Universidad Nacional Autónoma de México, CNyN-UNAM, Ensenada, Mexico.
J Biomed Mater Res B Appl Biomater. 2020 Aug;108(6):2396-2406. doi: 10.1002/jbm.b.34572. Epub 2020 Feb 4.
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 Y O codoped with Eu 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 Y O codoped with Eu and we conclude that these nanoparticles are biocompatible and can be further used for cancer cells bioimaging.
上转换发光纳米粒子（DCNPs）提供了高发光强度、尖锐的发射峰和窄带宽以及大斯托克斯位移的组合，导致高性能的生物医学应用，主要用于成像。本研究的目的是提出一种关于 Y O 共掺 Eu 的 DCNPs 的纳米毒理学研究，并对其进行功能化修饰以结合叶酸（FA）。这些评估包括细胞毒性、遗传毒性、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。它们通过溶胶-凝胶法合成，并涂覆有薄的二氧化硅壳以使其具有生物相容性；还通过氨基和 FA 配体进行功能化，这些配体与研究的癌细胞表面的叶酸受体（FR）结合。这种功能化使 DCNPs 能够通过与 FR 结合的内吞作用被内化到癌细胞中。通过透射电子显微镜、傅里叶变换红外光谱和光致发光对 DCNPs 进行了表征。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，在测试浓度（0.01-20 μg/mL）下，两种纳米粒子（裸纳米粒子和功能化纳米粒子）均无细胞毒性和遗传毒性。此外，它们具有血液相容性，并且不会在体外通过巨噬细胞产生一氧化氮。FA-DCNPs 明显定位于细胞质中，呈现明亮的红色发光。因此，本文对共掺 Eu 的 FA-DCNPs 进行了全面的纳米毒理学研究，并得出结论，这些纳米粒子具有生物相容性，可进一步用于癌细胞生物成像。
