We have synthesized gadolinium oxysulfide nanoparticles (NPs) doped with other lanthanides (Eu(3+), Er(3+), Yb(3+)) via a hydroxycarbonate precursor precipitation route followed by a sulfuration process under a H2S-Ar atmosphere at 750 °C in order to propose new multimodal nanoplatforms for Magnetic Resonance (MR), X-ray and photoluminescence imaging. Gd2O2S:Eu(3+) NPs strongly absorb near UV (≈ 300-400 nm) and re-emit strong red light (624 nm). They can be easily internalized by cancer cells, and imaged by epifluorescence microscopy under excitation in the NUV (365 nm). They are not cytotoxic for living cells up to 100 μg mL(-1). Consequently, they are well adapted for in vitro imaging on cell cultures. Gd2O2S:Eu(3+) NPs also show strong transverse relaxivity and strong X-ray absorption allowing their use as contrast agents for T2-weighted MRI and X-ray tomography. Our study shows that Gd2O2S:Eu(3+) NPs are considerably better than commercial Ferumoxtran-10 NPs as negative contrast agents for MRI. Upconversion emission of Gd2O2S:Er; Yb (1; 8%) NPs under infrared excitation (λ(ex) = 980 nm) shows mainly red emission (≈ 650-680 nm). Consequently, they are more specifically designed for in vivo deep fluorescence imaging, because both excitation and emission are located inside the "transparency window" of biological tissues (650-1200 nm). Magnetic relaxivity and X-ray absorption behaviors of Gd2O2S:Er; Yb NPs are almost similar to Gd2O2S:Eu(3+) NPs.

Europium-doped gadolinium carbonates particles have been prepared via urea-assisted precipitation. The reaction has been followed step by step with the investigations of the precipitate by transmission electron microscopy and wide-angle X-ray scattering, in relation with infrared absorption and thermal analyses. It has been observed that spherical particles of (Gd0.95Eu0.05)(OH)CO3, monodispersed in size and amorphous, precipitate first and then transform to agglomerated platelike crystals of (Gd0.95Eu0.05)2(CO3)3·2H2O as the precipitation continues. The Eu3+ 5D0 → 7FJ emission spectrum and the 5D0 lifetime in the two carbonate matrices have been measured. Selected hydroxycarbonate nanoparticles (NPs), with diameters of 164 ± 20 nm, have been then transformed to oxide NPs having the cubic crystalline structure C-(Gd0.95Eu0.05)2O3, with the same shape and size. The photoluminescence (PL) properties of hydroxycarbonate and oxide NPs, and of their colloidal suspensions in water, have been investigated. The hydroxycarbonate and the oxide NPs exhibit same PL intensities when excitation is achieved in one of the Eu3+(4f6) levels. Tests of in vitro fluorescence imaging have been performed. The luminescent NPs have been observed after their internalization by human cervical carcinoma (HeLa) cells. It is concluded that the controlled (urea-assisted) precipitation is appropriate to synthesize Gd(OH)CO3:Eu3+ and Gd2O3:Eu3+ nanoparticles having adequate characteristics for biolabeling.

The synthesis of Gd 2 O 2 S:Eu 3+ nanoparticles (NPs), from hydroxycarbonate precursor precipitation followed by sulfuration in a H 2 S/Ar atmosphere at 750 C; is reported. It is the first time that the size of Gd 2 O 2 S:Eu 3+ NPs can be finely tuned from 60 nm to more than 200 nm by controlling the precipitation medium, the maturation time and the sulfuration route. The oxysulfide Gd 2 O 2 S:Eu 3+ NPs emit strong red luminescence at 624 nm when excited by near UV (363 nm) or by X-rays. They may thus be considered as nano-phosphors and nano-scintillators. Then, the surface of oxysulfide NPs has been modified by an amino-silica or by a mesoporous silica shell (thickness 10-15 nm). The luminescence intensity of europium in gadolinium oxysulfide NPs has been maintained in the amino-silica coated particles Gd 2 O 2 S:Eu 3+ @SiO 2 -APTMS, whereas it has been significantly enhanced in the mesoporous silica coated Gd 2 O 2 S:Eu 3+ @mSiO 2 . This versatile new nanoplatform can be easily internalized in living NIH3T3 mouse cells. It is not cytotoxic up to 1 mg mL À1 and can be easily imaged by epifluorescence microscopy with excitation in the NUV. Consequently this spherical monodispersed Gd 2 O 2 S:Eu 3+ nanophosphor could be considered as a very promising new fluorescent probe for bio-labelling, better than the corresponding oxide or fluoride nanoparticles.

Time-gated luminescence microscopy using long-lifetime molecular probes can effectively eliminate autofluorescence to enable high contrast imaging. Here we investigate a new strategy of time-gated imaging for simultaneous visualisation of multiple species of microorganisms stained with long-lived complexes under low-background conditions. This is realized by imaging two pathogenic organisms (Giardia lamblia stained with a red europium probe and Cryptosporidium parvum with a green terbium probe) at UV wavelengths (320–400 nm) through synchronization of a flash lamp with high repetition rate (1 kHz) to a robust time-gating detection unit. This approach provides four times enhancement in signal-to-background ratio over non-time-gated imaging, while the average signal intensity also increases six-fold compared with that under UV LED excitation. The high sensitivity is further confirmed by imaging the single europium-doped Y2O2S nanocrystals (150 nm). We report technical details regarding the time-gating detection unit and demonstrate its compatibility with commercial epi-fluorescence microscopes, providing a valuable and convenient addition to standard laboratory equipment.

To cite this version:Chrystelle Neaime, Maria Amela-Cortes, Fabien Grasset, Yann Molard, Stéphane Cordier, et al..Time-gated luminescence bioimaging with new luminescent nanocolloids based on [Mo6I8(C2F5COO)(6)](2-) metal atom clusters.

Despite a clear development of innovative therapies based on stem cell manipulation, the availability of new tools to better understand and follow stem cell behavior and improve their biomedical applications is not adequate. Indeed, an ideal tracking device must have good ability to label stem cells as well as complete neutrality relative to their biology. Furthermore, preclinical studies imply in vitro and in vivo approaches that often require several kinds of labeling and/or detection procedures. Consequently, the multimodality concept presented in this work may present a solution to this problem as it has the potential to combine complementary imaging techniques. Spherical europium-doped gadolinium oxysulfide (Gd2O2S:Eu3+) nanoparticles are presented as a candidate as they are detectable by (1) magnetic resonance (MRI), (2) X-ray and (3) photoluminescence imaging. Whole body in vivo distribution, elimination and toxicity evaluation revealed a high tolerance of nanoparticles with a long-lasting MRI signal and slow hepatobiliary and renal clearance. In vitro labeling of a wide variety of cells unveils the nanoparticle potential for efficient and universal cell tracking. Emphasis on mesenchymal stromal cells (MSCs) leads to the definition of optimal conditions for labeling and tracking in the context of cell therapy: concentrations below 50 μg mL-1 and diameters between 170 and 300 nm. Viability, proliferation, migration and differentiation towards mesodermal lineages are preserved under these conditions, and cell labeling appears to be persistent and without any leakage. Ex vivo detection of as few as five thousand Gd2O2S:Eu3+-labeled MSCs by MRI combined with in vitro examination with fluorescence microscopy highlights the feasibility of cell tracking in cell therapy using this new nanoplatform.

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Europium-doped lanthanide oxide RE(2)O(3):Eu(3+) (RE = Y or Gd) luminescent beads, with a spherical shape and a diameter of 150 ± 15 nm, have been modified by reaction with 3-aminopropyltriethoxysilane (APTES), in order to introduce reactive amine groups at their surfaces. The direct silanation has resulted in the formation of a nanometric layer at the surface of the beads, with an optimum grafting rate of 0.055 ± 0.005 mol APTES/mol RE(2)O(3). Fourier transform infrared (FTIR) and X-ray photoelectron (XPS) spectroscopies confirmed the condensation of an organosilane layer, made of cross-linked -O-Si-O-Si- and of groups -O-Si-R (with R = (CH(2))(3)NH(2) or O-Et). Titration of the accessible amine groups has been performed by simultaneously measuring the luminescence of grafted fluorescein isothiocyanate and that of core particles: there are about 2.3 × 10(4) (2.8 × 10(4)) -NH(2) per Y(2)O(3):Eu(3+) (Gd(2)O(3):Eu(3+)) bead. The isoelectronic point was shifted by one pH unit after APTES modification. The surface modification by APTES at least preserved (for Gd(2)O(3):Eu(3+)) or improved (for Y(2)O(3):Eu(3+)) the red emission of the beads.