Calcium fluoride based multifunctional nanoparticles for multimodal imaging

Abstract

New multifunctional nanoparticles (NPs) that can be used as contrast agents (CA) in different imaging techniques, such as photoluminescence (PL) microscopy and magnetic resonance imaging (MRI), open new possibilities for medical imaging, e.g., in the fields of diagnostics or tissue characterization in regenerative medicine. The focus of this study is on the synthesis and characterization of CaF2:(Tb3+,Gd3+) NPs. Fabricated in a wet-chemical procedure, the spherical NPs with a diameter of 5–10 nm show a crystalline structure. Simultaneous doping of the NPs with different lanthanide ions, leading to paramagnetism and fluorescence, makes them suitable for MR and PL imaging. Owing to the Gd3+ ions on the surface, the NPs reduce the MR T 1 relaxation time constant as a function of their concentration. Thus, the NPs can be used as a MRI CA with a mean relaxivity of about r = 0.471 mL·mg−1·s−1. Repeated MRI examinations of four different batches prove the reproducibility of the NP synthesis and determine the long-term stability of the CAs. No cytotoxicity of NP concentrations between 0.5 and 1 mg·mL−1 was observed after exposure to human dermal fibroblasts over 24 h. Overall this study shows, that the CaF2:(Tb3+,Gd3+) NPs are suitable for medical imaging.

Luminescent Supraparticles Based on CaF2–Nanoparticle Building Blocks as Code Objects with Unique IDs

“…The synthesis, which is detailed in the Experimental Section, was done, using a slightly modified continuous precipitation method, which was published elsewhere. 26,30 Nanoparticles with sizes around 30 nm were obtained (transmission electron microscopy (TEM) images can be found in the Supporting Information (SI) Figure S1).…”

“…23−25 Due to its low phonon energy, quenching of the rare earth ion excited states is minimized. 26 In contrast to frequently used alkaline earth metal fluorides like NaYF 4 , the rare earth free matrix CaF 2 does not require cost-intensive purification of the precursors, as it is the case for yttrium, where such purification steps are necessary to exclude rare earth impurities which could otherwise negatively interfere with the luminescence color and efficiency of the phosphor system. 27 This is why Eu, Tm, Dy, Tb, and Sm doped CaF 2 nanoparticles were synthesized and characterized.…”

Bimodal Ultrasound and X-ray Bioimaging Properties of Particulate Calcium Fluoride Biomaterial

“…Therefore, this material holds tremendous promise for biomedical applications. For instance, it was tested for wound healing when formulated in hydrogels [20], 19 F magnetic resonance imaging [21], photoluminescence biosensing when doped with Mn 2+ [22], biomedical imaging when doped by Tb 3+ /Gd 3+ [23], and for targeted labeling of cancer cells when doped with Eu 3+ [12]. Due to its high fluorine content, most of the studies are limited to the potential of calcium fluoride in dental applications [16,[24][25][26].…”

Absolute Luminescence Efficiency of Europium-Doped Calcium Fluoride (CaF2:Eu) Single Crystals under X-ray Excitation

“…Up until now, CaF has been used in a limited number of biomedical applications [22][23][24][25][43][44][45][46][47][48][49][50][51][52]. For example, CaF 2 has been applied in conjunction with SiPMs in gamma spectrometry, and due to its biocompatibility and the stability of the material, it has proven to be significant for fluorescent labeling in biological applications.…”