Clearable Shortwave-Infrared-Emitting NaErF4 Nanoparticles for Noninvasive Dynamic Vascular Imaging

Nanoprobes with emissions in the tissue-penetrating shortwave infrared (SWIR, 1000-1700 nm) range hold promise for noninvasive angiographic imaging of small animals. However, limited success has been achieved in SWIR-emitting contrast agents beyond 1500 nm that can be cleared out from the body. Here, we describe a class of clearable, 1525 nm-emitting NaErF4-based nanoparticles that enable dynamic vasculature imaging of the whole body at a high spatial resolution (similar to 58 mu m) under biocompatible 808 nm excitation (avoiding the biological heating effect with typically used 980 nm excitation). We made a systematic investigation of the effects of the crystal phase (hexagonal and cubic), the core@shell structure, the lattice mismatch between the core and the shell (NaLnF(4), Ln = Y, Lu, or Gd), and the shell thickness on SWIR luminescence. The brightest nanoparticles were determined to be hexagonal (beta)-phase core@shell NaErF4@NaYF4 nanoparticles (beta-Er@Y-NPs, size 13 nm) that have the lowest core@shell lattice mismatch and a shell thickness of similar to 3 nm, presenting SWIR luminescence about similar to 180-fold higher than that of the parent core NPs. Intravenous (IV) administration of aqueous beta-Er@Y-NPs (at a dose of 5 mg/kg) enabled a clear through-skull brain vessel imaging without craniotomy and dynamic vasculature imaging of the whole body. A pharmacokinetic study indicates a near-complete clearance of these core@shell nanoparticles primarily through feces at 14 days post IV injection. Histological studies of internal organ tissues (heart, liver, spleen, lung, and kidney) and blood biochemical analysis demonstrate low toxicities of these NPs. Our results here provide a new class of clearable SWIR-emitting NPs as imaging contrast agents for high-resolution in vivo biological studies.