Synthesis of europium-doped VSOP, customized enhancer solution and improved microscopy fluorescence methodology for unambiguous histological detection

• Published in: Journal of nanobiotechnology Vol. 15; no. 1; p. 71
• Main Authors: de Schellenberger, Angela Ariza, Hauptmann, Ralf, Millward, Jason M, Schellenberger, Eyk, Kobayashi, Yuske, Taupitz, Matthias, Infante-Duarte, Carmen, Schnorr, Jörg, Wagner, Susanne
• Format: Journal Article
• Language: English
• Published: England BioMed Central 10.10.2017; BMC
• Subjects: Animals; Buffers; Cell cycle; Chemical industry; Contrast agents; Europium; Europium - analysis; Europium - pharmacokinetics; Ferric Compounds - analysis; Ferric Compounds - chemical synthesis; Ferric Compounds - pharmacokinetics; Fluorescence; Identification methods; Iron; Iron oxides; Localization; Mathematical analysis; Medical imaging; Methodology; Mice; Mice, Inbred C57BL; Microscopy; Microscopy, Fluorescence - methods; MRI; Multiple sclerosis; Nanoparticles; Nanoparticles - analysis; Nanoparticles - ultrastructure; Nanotechnology - methods; NMR; Nuclear magnetic resonance; RAW 264.7 Cells; Surface charge; Tissue Distribution; Tissues; Toxicology; VSOP; Wavelength; Fluorescence; MRI; Europium; VSOP
• ISSN: 1477-3155; 1477-3155
• 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.