Molecularly targeted nanophosphors that produce X-ray excited optical luminescence (XEOL) enable unique multimodal imaging capabilities, such as combined optical/fluoroscopic or optical/CT imaging. Here we present the synthesis and characterization of a poly(ethylene glycol) (PEG)-coated BaYF5 nanoparticle platform to serve as a XEOL probe. In this system, optical emission can be tuned by selection of lanthanide dopants, such as Eu3+. BaYF5 core particles were synthesized by the thermal decomposition method using lanthanide trifluoroacetates, barium acetylacetonate, oleic acid and 1-octadecene. Uniform cubic (~10 nm) nanocyrstals were obtained by this process and observed by transmission electron microscopy (TEM, Fig. 1A). A solvent exchange process using dicarboxyl functionalized PEG was then preformed to produce hydrophilic and colloidal aqueous suspensions of the nanophosphors (Fig. 1B & C). Incorporating a biocompatible PEG coating bearing carboxyl functional groups, this nanophosphor platform possesses the ability to attach a variety of targeting and other biological ligands through conventional bioconjugate techniques. To evaluate the XEOL of these nanophosphors a suspension of the particles was irradiated at 50 kVp while an emission spectrum (Fig. 1D) was obtained by a spectrograph coupled to an EM-CCD. Strong peaks were observed at 590, 615 and 700 nm with the BaYF5:Eu3+ nanophosphors. Of particular interest, emission at 700 nm in the near-infrared region provides significant tissue penetration necessary for in vivo applications. In summary, a PEG-coated nanophosphor was developed with physical and optical properties required to serve as an XEOL molecular imaging probe. Luminescent nanophosphors may enable multimodal x-ray/optical imaging, as well as a wide range of other applications in molecular imaging and nanomedicine.

Figure 1 - (A) TEM of PEG-coated BaYF5:Eu3+ nanophosphors. (B) Illustration of PEG-COOH functionalized nanophosphor for bioconjugation. (C) Dispersion of 1 mg/mL hydrophilic nanophosphors in water. (D) X-ray exited luminescence spectra.