de Schellenberger Angela Ariza, Hauptmann Ralf, Millward Jason M, Schellenberger Eyk, Kobayashi Yuske, Taupitz Matthias, Infante-Duarte Carmen, Schnorr Jörg, Wagner Susanne
Department of Radiology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Charitéplatz 1, 10117, Berlin, Germany.
Berlin Ultrahigh Field Facility, Max Delbrück Center for Molecular Medicine, Robert-Rössle-Str. 10, 13125, Berlin, Germany.
J Nanobiotechnology. 2017 Oct 10;15(1):71. doi: 10.1186/s12951-017-0301-6.
Intrinsic iron in biological tissues frequently precludes unambiguous the identification of iron oxide nanoparticles when iron-based detection methods are used. Here we report the full methodology for synthesizing very small iron oxide nanoparticles (VSOP) doped with europium (Eu) in their iron oxide core (Eu-VSOP) and their unambiguous qualitative and quantitative detection by fluorescence.
The resulting Eu-VSOP contained 0.7 to 2.7% Eu relative to iron, which was sufficient for fluorescent detection while not altering other important particle parameters such as size, surface charge, or relaxivity. A customized enhancer solution with high buffer capacity and nearly neutral pH was developed to provide an antenna system that allowed fluorescent detection of Eu-VSOP in cells and histologic tissue slices as well as in solutions even under acidic conditions as frequently obtained from dissolved organic material. This enhancer solution allowed detection of Eu-VSOP using a standard fluorescence spectrophotometer and a fluorescence microscope equipped with a custom filter set with an excitation wavelength (λ) of 338 nm and an emission wavelength (λ) of 616 nm.
The fluorescent detection of Eu-doped very small iron oxide nanoparticles (Eu-VSOP) provides a straightforward tool to unambiguously characterize VSOP biodistribution and toxicology at tissue, and cellular levels, providing a sensitive analytical tool to detect Eu-doped IONP in dissolved organ tissue and biological fluids with fluorescence instruments.
当使用基于铁的检测方法时，生物组织中的内源性铁常常妨碍对氧化铁纳米颗粒进行明确鉴定。在此，我们报告了在其氧化铁核心中掺杂铕（Eu）的超小氧化铁纳米颗粒（VSOP）（Eu-VSOP）的完整合成方法，以及通过荧光对其进行明确的定性和定量检测。
所得的Eu-VSOP相对于铁含有0.7%至2.7%的Eu，这足以进行荧光检测，同时不会改变其他重要的颗粒参数，如尺寸、表面电荷或弛豫率。开发了一种具有高缓冲能力和接近中性pH值的定制增强剂溶液，以提供一种天线系统，即使在溶解有机物质经常导致的酸性条件下，也能在细胞和组织切片以及溶液中对Eu-VSOP进行荧光检测。这种增强剂溶液允许使用标准荧光分光光度计和配备定制滤光片组的荧光显微镜检测Eu-VSOP，激发波长（λ）为338 nm，发射波长（λ）为616 nm。
铕掺杂的超小氧化铁纳米颗粒（Eu-VSOP）的荧光检测提供了一种直接的工具，可在组织和细胞水平上明确表征VSOP的生物分布和毒理学，为使用荧光仪器检测溶解器官组织和生物流体中的铕掺杂IONP提供了一种灵敏的分析工具。
