Luminescence properties of Eu-complex formations into ordered mesoporous silica particles obtained by the spray pyrolysis process.

Ordered mesoporous, highly luminescent SiO2 particles have been synthesized by spray pyrolysis from solutions containing tetraethylorthosilicate (TEOS), Eu(NO3)3.6H2O, and cetyltrimethylammonium bromide (CTAB) as structure-directing agents. The 1,10-phenantroline (Phen) molecules were coordinated in a post-synthesis step by a simple wet impregnation method. In addition, other matrices were also prepared by the encapsulation of europium complex Eu(fod)3 (where fod = 6,6,7,7,8,8,8-heptafluoro-2,2-dimethyl-3,5-octanedionato) into mesoporous silica, and then the Phen molecules were encapsulated by different impregnation steps, after which the luminescence properties were investigated. The obtained materials were characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), powder x-ray diffraction (XRD) and Fourier transform infrared (FTIR) spectroscopy. Powders with polydisperse spherical grains were obtained, displaying an ordered hexagonal array of mesochannels. Luminescence results revealed that Phen molecules had been successfully coordinated as an additional ligand in the Eu(fod)3 complex into the channels of the mesoporous particles without disrupting the structure.

Novel contributions on luminescent apatite-based colloids intended for medical imaging.

The setup of colloidal hybrid nanosystems based on biomimetic calcium phosphate apatites doped with europium ions has recently raised great interest in the pharmacological community, especially due to their bio-inspired character. This is especially relevant in relation with medical imaging for cancer diagnosis. Questions however remain in relation to a number of applicability aspects, some of which have been examined in this contribution. In a first part of this work, we explored further the luminescence properties of such colloidal nanoparticles. We pointed out, upon excitation of europium, the existence of some non-radiative de-excitation via the vibration of O-H oscillators located at the vicinity of the Eu(3+) luminescent centers. The replacement of Eu(3+) by Tb(3+) ions, less prone to non-radiative de-excitation, was then tested in a preliminary way and can be seen as a promising alternative. In a second part of this work, we inspected the possibility to store these colloids in a dry state while retaining a re-suspension ability preserving the nanometer size of the initial nanoparticles, and we propose a functional protocol involving the addition of glucose prior to freeze-drying. We finally showed for the first time, based on titrations of intracellular Ca(2+) and Eu(3+) ions, that folic acid-functionalized biomimetic apatite nanoparticles were able to target cancer cells that overexpress folate receptors on their membrane, which we point out here in the case of T-47-D breast carcinoma cells, as opposed to ZR-75-1 cells that do not express folate receptors. This contribution thus opens new exciting perspectives in the field of targeted cancer diagnosis, thus confirming the promise of biomimetic apatites-based colloidal formulations.

Gadolinium oxysulfide nanoparticles as multimodal imaging agents for T2-weighted MR, X-ray tomography and photoluminescence.

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.

Organosilylated complex [Eu(TTA)3(Bpy-Si)]: a bifunctional moiety for the engeneering of luminescent silica-based nanoparticles for bioimaging.

A new highly luminescent europium complex with the formula [Eu(TTA)3(Bpy-Si)], where TTA stands for the thenoyltrifluoroacetone, (C4H3S)COCH2COCF3, chelating ligand and Bpy-Si, Bpy-CH2NH(CH2)3Si(OEt)3, is an organosilyldipyridine ligand displaying a triethoxysilyl group as a grafting function has been synthesized and fully characterized. This bifunctional complex has been grafted onto the surface of dense silica nanoparticles (NPs) and on mesoporous silica microparticles as well. The covalent bonding of [Eu(TTA)3(Bpy-Si)] inside uniform Stöber silica nanoparticles was also achieved. The general methodology proposed could be applied to any silica matrix, allowed high grafting ratios that overcome chelate release and the tendency to agglomerate. Luminescent silica-based nanoparticles SiO2-[Eu(TTA)3(Bpy-Si)], with a diameter of 28 ± 2 nm, were successfully tested as a luminescent labels for the imaging of Pseudomonas aeruginosa biofilms. They were also functionalized by a specific monoclonal antibody and subsequently employed for the selective imaging of Escherichia coli bacteria.

APTES-modified RE2O3:Eu3+ luminescent beads: structure and properties.

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.

Biomimetic nanocrystalline apatites: Emerging perspectives in cancer diagnosis and treatment.

Nanocrystalline calcium phosphate apatites constitute the mineral part of hard tissues, and the synthesis of biomimetic analogs is now well-mastered at the lab-scale. Recent advances in the fine physico-chemical characterization of these phases enable one to envision original applications in the medical field along with a better understanding of the underlying chemistry and related pharmacological features. In this contribution, we specifically focused on applications of biomimetic apatites in the field of cancer diagnosis or treatment. We first report on the production and first biological evaluations (cytotoxicity, pro-inflammatory potential, internalization by ZR-75-1 breast cancer cells) of individualized luminescent nanoparticles based on Eu-doped apatites, eventually associated with folic acid, for medical imaging purposes. We then detail, in a first approach, the preparation of tridimensional constructs associating nanocrystalline apatite aqueous gels and drug-loaded pectin microspheres. Sustained releases of a fluorescein analog (erythrosin) used as model molecule were obtained over 7 days, in comparison with the ceramic or microsphere reference compounds. Such systems could constitute original bone-filling materials for in situ delivery of anticancer drugs.

Alteration of enzyme activity and enantioselectivity by biomimetic encapsulation in silica particles.

Direct encapsulation of esterase or lipase fused with the silica-precipitating R5 peptide from Cylindrotheca fusiformis in silica particles afforded high yields of active entrapped protein. The hydrolytic activity of both enzymes against p-nitrophenyl butyrate was similarly affected by encapsulation and the enantioselectivity of the esterase was both improved and inverted.

Europium(III) complexes containing organosilyldipyridine ligands grafted on silica nanoparticles.

This work focuses on the grafting of transition metal complexes on silica surface nanoparticles. Nanoscale silica particles in aqueous sols are used as starting silicated materials. We have undertaken the synthesis of europium(III) complexes containing organosilyldipyridine ligands, (EtO)3Si(CH2)3NHCH2-bipy (1) and (EtO)(CH3)2Si(CH2) 3NHCH 2-bipy (2), in view of a direct grafting reaction on silica nanoparticles. Reaction of one molar equivalent of 1 and 2 with Eu(tmhd)3 (tmhd= 2,2,6,6-tetramethyl-3,5-heptanedionato), as precursor, leads to octacoordinated silylated europium(III) complexes [Eu(tmhd)3(1)] (3) and [Eu(tmhd)3(2)] (4) as white solids in 34-54% yields. Europium complexes were characterized by elemental analysis, mass spectrometry, FT-IR, UV, and luminescence spectroscopies. These new complexes are reacting in a 1:10 (v/v) water and ethanol mixture with silica nanoparticles colloidal sol. Elemental analysis and thermogravimetric data indicated grafting ratios of 0.41 and 0.26 mmol of europium(III) complexes per gram of silica. Functionalized silica nanoparticles were characterized by DRIFT spectroscopy and TEM microscopy. The first analysis shows that the chemical integrity of the complexes is retained on the silica surface together with the size and the monodispersity of the nanoscale particles. As expected for europium(III) complexes, luminescence is observed under UV irradiation. Emission and excitation spectra indicate that the metal coordination environment is not modified on the silica surface. Moreover, the sharpness of the luminescence bands and the strong antenna effect are maintained when complexes are covalently bonded to silica. New luminescent europium(III) complexes grafted on silica nanoparticles are therefore obtained from our approach.