NaGdF4:Eu3+ Nanoparticles for Enhanced X-ray Excited Optical Imaging.

X-ray luminescent nanoparticles (NPs), including lanthanide fluorides, have been evaluated for application to deep tissue in vivo molecular imaging using optical tomography. A combination of high material density, higher atomic number and efficient NIR luminescence from compatible lanthanide dopant ions indicates that particles that consist of ALnF4 (A = alkaline, Ln = lanthanide element) may offer a very attractive class of materials for high resolution, deep tissue imaging with X-ray excitation. NaGdF4:Eu3+ NPs produced an X-ray excited luminescence that was among the most efficient of nanomaterials that have been studied thus far. We have systematically studied factors such as (a) the crystal structure that changes the lattice environment of the doped Eu3+ ions within the unit cell; and extrinsic factors such as (b) a gold coating (with attendant biocompatibility) that couples to a plasmonic excitation, and (c) changes in the NPs surface properties via changes in the pH of the suspending medium-all with a significant impact on the X-ray excited luminescence of NaGdF4:Eu3+NPs. The luminescence from an optimally doped hexagonal phase NaGdF4:Eu3+ nanoparticle was 25% more intense compared to that of a cubic structure. We observed evidence of plasmonic reabsorption of midwavelength emission by a gold coating on hexagonal NaGdF4:Eu3+ NPs; fortunately, the NaGdF4:Eu3+ @Au core-shell NPs retained the efficient 5D0→7F4 NIR (692 nm) luminescence. The NaGdF4:Eu3+ NPs exhibited sensitivity to the ambient pH when excited by X-rays, an effect not seen with UV excitation. The sensitivity to the local environment can be understood in terms of the sensitivity of the excitons that are generated by the high energy X-rays (and not by UV photons) to crystal structure and to the surface state of the particles

Novel lanthanide-labeled metal oxide nanoparticles improve the measurement of in vivo clearance and translocation

Abstract The deposition, clearance and translocation of europium-doped gadolinium oxide nanoparticles in a mouse lung were investigated experimentally. Nanoparticles were synthesized by spray flame pyrolysis. The particle size, crystallinity and surface properties were characterized. Following instillation, the concentrations of particles in organs were determined with inductively coupled plasma mass spectrometry. The protein corona coating the nanoparticles was found to be similar to the coating on more environmentally relevant nanoparticles such as iron oxide. Measurements of the solubility of the nanoparticles in surrogates of biological fluids indicated very little propensity for dissolution, and the elemental ratio of particle constituents did not change, adding further support to the contention that intact nanoparticles were measured. The particles were intratracheally instilled into the mouse lung. After 24 hours, the target organs were harvested, acid digested and the nanoparticle mass in each organ was measured by inductively coupled plasma mass spectrometry (ICP-MS). The nanoparticles were detected in all the studied organs at low ppb levels; 59% of the particles remained in the lung. A significant amount of particles was also detected in the feces, suggesting fast clearance mechanisms. The nanoparticle system used in this work is highly suitable for quantitatively determining deposition, transport and clearance of nanoparticles from the lung, providing a quantified measure of delivered dose.</p

Potential toxicity of up-converting nanoparticles encapsulated with a bilayer formed by ligand attraction.

The cellular toxicity of nanoparticles that were capped with a bilayered ligand was studied using an up-converting (UC) phosphor material as a representative nanoparticle (NP). The results indicate that although UC NPs are known to be nontoxic, the toxicity of the NPs depends strongly on ligand coordination conditions, in addition to the other commonly known parameters such as size, structure, surface charge etc. Oleate-capped hydrophobic NaYF4:Yb,Er NPs were surface modified to yield three extreme conditions: bare particles that were stripped of the oleate ligands; particles with covalently bound poly(ethylene glycol) (PEG) ligands; and particles with an bilayer of PEG-oleate ligands using the oleate surface group that was remained after synthesis. It was found that the bare particles and the covalent PEG NPs induced little toxicity. However, particles that were rendered biocompatible by forming a bilayer with an amphiphilic ligand (i.e., PEG-oleate) resulted in significant cell toxicity. These findings strongly suggest that the PEG-oleate group dissociated from the bilayered oleate-capped NPs, resulting in significant toxicity by exposing the hydrophobic oleate-capped NPs to the cell. Based on results with bare particles, the NaLnF4:Yb,Er (Ln = Y, Gd) up-converting phosphors are essentially less-toxic. Capping and functionalizing these particles with ligand intercalation may, however, not be a suitable method for rendering the NPs suitable for bioapplication as the ligand can potentially dissociate upon cellular interaction, leading to significant toxicity

Potential Toxicity of Up-Converting Nanoparticles Encapsulated with a Bilayer Formed by Ligand Attraction

The cellular toxicity of nanoparticles that were capped with a bilayered ligand was studied using an up-converting (UC) phosphor material as a representative nanoparticle (NP). The results indicate that although UC NPs are known to be nontoxic, the toxicity of the NPs depends strongly on ligand coordination conditions, in addition to the other commonly known parameters such as size, structure, surface charge etc. Oleate-capped hydrophobic NaYF₄:Yb,Er NPs were surface modified to yield three extreme conditions: bare particles that were stripped of the oleate ligands; particles with covalently bound poly­(ethylene glycol) (PEG) ligands; and particles with an bilayer of PEG-oleate ligands using the oleate surface group that was remained after synthesis. It was found that the bare particles and the covalent PEG NPs induced little toxicity. However, particles that were rendered biocompatible by forming a bilayer with an amphiphilic ligand (i.e., PEG-oleate) resulted in significant cell toxicity. These findings strongly suggest that the PEG-oleate group dissociated from the bilayered oleate-capped NPs, resulting in significant toxicity by exposing the hydrophobic oleate-capped NPs to the cell. Based on results with bare particles, the NaLnF₄:Yb,Er (Ln = Y, Gd) up-converting phosphors are essentially less-toxic. Capping and functionalizing these particles with ligand intercalation may, however, not be a suitable method for rendering the NPs suitable for bioapplication as the ligand can potentially dissociate upon cellular interaction, leading to significant toxicity

Single-phase NaDyF4:Tb3+ nanocrystals as multifunctional contrast agents in high-field magnetic resonance and optical imaging

The current work reports single-phase, terbium-doped sodium dysprosium fluoride (NaDyF4:Tb3+) nanocrystals with green luminescence and good T2 contrast in 7.0-T MRI phantom and animal imaging. The current nanocrystals demonstrate good potential as a dual modal contrast agent for high-field magnetic resonance (MR) and fluorescence imaging

NaGdF4:Eu 3+ Nanoparticles for Enhanced X‑ray Excited Optical Imaging

ABSTRACT: X-ray luminescent nanoparticles (NPs), including lanthanide fluorides, have been evaluated for application to deep tissue in vivo molecular imaging using optical tomography. A combination of high material density, higher atomic number and efficient NIR luminescence from compatible lanthanide dopant ions indicates that particles that consist of ALnF4 (A = alkaline, Ln = lanthanide element) may offer a very attractive class of materials for high resolution, deep tissue imaging with X-ray excitation. NaGdF4:Eu 3+ NPs produced an X-ray excited luminescence that was among the most efficient of nanomaterials that have been studied thus far. We have systematically studied factors such as (a) the crystal structure that changes the lattice environment of the doped Eu3+ ions within the unit cell; and extrinsic factors such as (b) a gold coating (with attendant biocompatibility) that couples to a plasmonic excitation, and (c) changes in the NPs surface properties via changes in the pH of the suspending mediumall with a significant impact on the X-ray excited luminescence of NaGdF4:Eu3+NPs. The luminescence from an optimally doped hexagonal phase NaGdF4:Eu 3+ nanoparticle was 25 % more intense compared to that of a cubic structure. We observed evidence of plasmonic reabsorption of midwavelength emission by a gold coating on hexagonal NaGdF4:Eu 3+ NPs; fortunately, the NaGdF4:Eu 3

NaGdF4:Eu3+ Nanoparticles for Enhanced X-ray Excited Optical Imaging.

X-ray luminescent nanoparticles (NPs), including lanthanide fluorides, have been evaluated for application to deep tissue in vivo molecular imaging using optical tomography. A combination of high material density, higher atomic number and efficient NIR luminescence from compatible lanthanide dopant ions indicates that particles that consist of ALnF4 (A = alkaline, Ln = lanthanide element) may offer a very attractive class of materials for high resolution, deep tissue imaging with X-ray excitation. NaGdF4:Eu3+ NPs produced an X-ray excited luminescence that was among the most efficient of nanomaterials that have been studied thus far. We have systematically studied factors such as (a) the crystal structure that changes the lattice environment of the doped Eu3+ ions within the unit cell; and extrinsic factors such as (b) a gold coating (with attendant biocompatibility) that couples to a plasmonic excitation, and (c) changes in the NPs surface properties via changes in the pH of the suspending medium-all with a significant impact on the X-ray excited luminescence of NaGdF4:Eu3+NPs. The luminescence from an optimally doped hexagonal phase NaGdF4:Eu3+ nanoparticle was 25% more intense compared to that of a cubic structure. We observed evidence of plasmonic reabsorption of midwavelength emission by a gold coating on hexagonal NaGdF4:Eu3+ NPs; fortunately, the NaGdF4:Eu3+ @Au core-shell NPs retained the efficient 5D0→7F4 NIR (692 nm) luminescence. The NaGdF4:Eu3+ NPs exhibited sensitivity to the ambient pH when excited by X-rays, an effect not seen with UV excitation. The sensitivity to the local environment can be understood in terms of the sensitivity of the excitons that are generated by the high energy X-rays (and not by UV photons) to crystal structure and to the surface state of the particles