Nanoparticles consisting of either a solid core of GdF3 or an 80/20 mixture of GdF3 and LaF3 have been prepared for use as NMR and MRI relaxation agents. To obtain high aqueous solubilities, the particles were coated with either citrate (cit) groups (in the case of GdF3 nanoparticles), giving the nanoparticle a negatively charged surface, or 2-aminoethyl phosphate (AEP) groups (in the case of GdF3/LaF3 = 80/20), giving the nanoparticle a positively charged surface at physiological pH. In the presence of the 80/20 GdF3/LaF3:AEP, the paramagnetic contribution to the water spin−lattice relaxation rate was observed to be 7.5 s-1 at a nanoparticle concentration of 9.0 nM (0.78 mg/mL, 25 °C, 600 MHz 1H Larmor frequency). Similarly, paramagnetic rates of 10.5 s-1 were observed for water using the GdF3:cit nanoparticles at a nanoparticle concentration of 0.55 nM (0.77 mg/mL, 25 °C, 600 MHz 1H Larmor frequency). Relaxivity measurements confirmed the potential of the particles for applications as contrast agents at MRI imaging field strengths. T 1 and T 2 experiments of the GdF3:cit revealed mass relaxivities of 7.4 ± 0.2 and 8.4 ± 0.2 s-1 (mg/mL)-1, respectively, at 1.5 T, whereas identical measurements at 3.0 T revealed respective relaxivities of 8.8 ± 0.2 and 9.4 ± 0.2 s-1 (mg/mL)-1. The relatively high mass relaxivities exhibited by the nanoparticles may also find uses in NMR studies in which spin−lattice relaxation times are prohibitively long, as in the case of highly deuterated proteins. Direct interaction with the protein can be minimized by the use of surface charges opposite to the net charge of the molecule, whereas the nanoparticles are easily removed by ultracentrifugation.

The preparation of nearly monodisperse (40 nm), silica-coated LaF(3):Ln(3+) nanoparticles and their bioconjugation to FITC-avidin (FITC=fluorescein isothiocyanate) is described in this report. Doping of the LaF(3) core with selected luminescent Ln(3+) ions allows the particles to display a range of emission lines from the visible to the near-infrared region (lambda=450-1650 nm). First, the use of Tb(3+) and Eu(3+) ions resulted in green (lambda=541 nm) and red (lambda=591 and 612 nm) emissions, respectively, by energy downconversion processes. Second, the use of Nd(3+) gave emission lines at lambda=870, 1070 and 1350 nm and Er(3+) gave an emission line at lambda=1540 nm by energy downconversion processes. Additionally, the Er(3+) ions gave green and red emissions and Tm(3+) ions gave an emission at lambda=800 nm by upconversion processes when codoped with Yb(3+) (lambda(ex)=980 nm). Bioconjugation of avidin, which has a bound fluorophore (FITC) as the reporter, was carried out by means of surface modification of the silica particles with 3-aminopropyltrimethoxysilane, followed by reaction with the biotin-N-hydroxysuccinimide activated ester to form an amide bond, imparting biological activity to the particles. A 25-fold or better increase in the FITC signal relative to the non-biotinylated silica particles indicated that there is minimal nonspecific binding of FITC-avidin to the silica particles.

The binding of Eu3+-doped LaF3 nanoparticles with biotin moieties at the surface of the stabilizing ligand layer to avidin, immobilized on cross-linked aragose beads, is described. The biotin moieties were attached to the nanoparticles by reaction of an activated ester with the amino groups on the surface of the nanoparticles resulting from the 2-aminoethyl phosphate ligands that were coordinated to the surface through the phosphate end. This strategy of employing the reactions of amines with activated esters provides a general platform to modify the surface of the 2-aminophosphate stabilized Ln3+-doped LaF3 nanoparticles with biologically relevant groups. Significant suppression of nonspecific binding to the avidin modified aragose beads has been realized by the incorporation of poly(ethylene glycol) units via the same reaction of a primary amine with an activated ester. The particle size distribution of the functionalized nanoparticles was within 10-50 nm, with a quantum yield of 19% in H2O for the LaF3 nanoparticles codoped with Ce3+ and Tb3+. A discreet, 4 unit poly(ethylene glycol) spaced heterobifunctional cross-linker, functionalized with biotin and N-hydroxysuccinimide at opposite termini, was covalently linked to the 2-aminoethyl phosphate ligand via the N-hydroxysuccinimide activated ester, making an amide bond, imparting biological activity to the particle. Modification of the remaining unreacted amino groups of the stabilizing ligands was done with Me(OCH2CH2)3CH2CH2(C=O)-NHS (NHS = N-hydroxysuccinimide).

The use of optically robust, luminescent lanthanide-based particles is becoming an area of interest for bio-label-related chemistry, due to their long lifetimes and range of non-overlapping absorption and emission lines from the visible to the near-infrared. We report the synthesis and optical properties of water-soluble, luminescent Ln(3+)-doped nanoparticles (NPs) coordinated with a hydrophilic (RO)PO(3) (2-) ligand that facilitates the stabilization of the NPs in aqueous conditions, and that regulates particle growth to the nanometer range. The use of lanthanide ions as dopants, in particular Eu(3+) and Er(3+) ions, yields optically robust particles with narrow emission lines in the visible (591 nm) and in the near-infrared (1530 nm), respectively. Luminescent lifetimes range from the microsecond to the millisecond for Er(3+) and Eu(3+) ions, respectively, and the NPs are not expected to be susceptible to photo-bleaching due to the fact that the emissions arise from intra-4f transitions of the lanthanide ions.

A general procedure is described for the synthesis and conversion of dispersible core/shell LaF3:Tm/LaF3 nanoparticles to highly dispersible thulium‐doped lanthanum disilicate nanoparticles (La2Si2O7:Tm) with an average diameter of 7 nm that show emission at a wavelength of 1.47 μm. Measurement of the citrate‐stabilized precursor nanoparticles in a KBr pellet shows a 1.47 μm emission with an effective lifetime of only 3 μs and an estimated quantum yield of ≪ 1 %. However, significant improvements to the emission properties are obtained by forming a ca. 1 nm thick silica shell around the nanoparticles via a modified Stöber method, followed by baking at 900 °C for 12 h to convert the LaF3 matrix to La2Si2O7. Excitation with a 785 nm continuous wave (CW) diode laser results in the luminescence of the 3H4–3F4 transition at 1.47 μm with an effective lifetime of 56 μs and an estimated quantum yield of 4 %. High‐resolution measurements at 77 K are carried out in order to improve the resolution of the crystal‐field splitting observed from the 3H4 level.