PEGylated β-NaGdF₄/Tb@CaF₂ Core/Shell Nanophosphors for Enhanced Radioluminescence and Folate Receptor Targeting

Abstract

Lanthanide-doped nanocrystals have been examined extensively as contrast agents for various optical molecular imaging techniques. One of the greatest strengths of these nanomaterials is their ability to enable novel imaging modalities, such as X-ray excited radioluminescence imaging, which leverages the exceptional tissue depth penetration of X-rays and reduced tissue autofluorescence. Here, we report a uniquely engineered NaGdF4/Tb@CaF2 nanoscintillator with substantial lattice mismatch through integration of coprecipitation and thermal decomposition synthetic routes. We observed greatly enhanced radioluminescence by the NaGdF4/15%Tb@CaF2 core/shell nanocrystals, which results from the minimized surface quenching and localized structure transformation. Polyethylene glycol coated NaGdF4/15%Tb@CaF2 nanocrystals demonstrated robust aqueous colloidal stability and were well tolerated by a panel of cell lines. The core/shell NaGdF4/15%Tb@CaF2 nanophosphors were subsequently decorated with targeting folate ligands and investigated as an X-ray luminescence imaging probe in vitro. Overall, the results suggest that these optimized radioluminescent nanophosphors have the potential to enable X-ray excited optical emission for biological imaging and serve as energy mediators in theranostic applications.

Hard X-ray excited optical luminescence from protein-directed Au∼20 clusters

“…3). 24 We observed clear contrast when using these protein-directed Au clusters; in particular, the albumindirected clusters displayed a slightly higher intensity ( Fig. 3a and b).…”

An Ultra‐Stable, Oxygen‐Supply Nanoprobe Emitting in Near‐Infrared‐II Window to Guide and Enhance Radiotherapy by Promoting Anti‐Tumor Immunity

“…[ 48 ] Conjugation with polyethylene glycol (8‐Arm PEG‐amine) molecules and tumor‐targeting arginine‐glycine‐aspartic (cyclo(RGDyK)) tripeptides imparted a targeting ability to the nanozyme to function as an effective in vivo nanoprobe for tumors. [ 49,50 ] After being injected in mice, the nanoprobes could specifically target 4T1 tumors and enhance the therapeutic efficacy of RT compared with X‐ray radiation alone, owing to the radiosensitive activity of the element Ag and the hypoxia relief in TME triggered by Mn (II) ions. [ 51 ] The bright fluorescence in the NIR‐II window enabled real‐time in vivo imaging with high‐clarity for monitoring the accumulation of nanoprobes in tumor sites after injection and guiding further RT treatment, which reduced unnecessary X‐ray irradiation and relieved side effects.…”

Focused x-ray luminescence imaging system for small animals based on a rotary gantry

“…Soon following, several research groups, including our own, improved several aspects of XLCT including the XLCT imaging systems, 3 – 13 robust reconstruction algorithms, 4 , 14 and designing efficient, bright, and biocompatible XLCT imaging probes. 15 – 20 …”

“…Smaller stable nanophosphors have also been developed for biolabeling applications, especially fluorescence and upconversion, and some of these (e.g., and ) are also good XLI contrast agents. 2 , 15 – 20 Reducing the phosphor size usually decreases their luminescence yield due to quenching from surface defects and escape of x-ray generated photoelectrons, but annealing processes can help by reducing quenching from defects. Based on our previous work with XLCT imaging, along with the efforts of our collaborators, we have proposed and are currently building a small-animal dedicated focused x-ray luminescence tomography (FXLT) imaging system that also incorporates a micro-computed tomography ( ) scanner.…”