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 (∼58 μm) 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 (NaLnF4, Ln = Y, Lu, or Gd), and the shell thickness on SWIR luminescence. The brightest nanoparticles were determined to be hexagonal (β)-phase core@shell NaErF4@NaYF4 nanoparticles (β-Er@Y-NPs, size 13 nm) that have the lowest core@shell lattice mismatch and a shell thickness of ∼3 nm, presenting SWIR luminescence about ∼180-fold higher than that of the parent core NPs. Intravenous (IV) administration of aqueous β-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.
Acute kidney injury (AKI) is a common kidney disease characterized by a sudden decline in renal function. It usually has no clear clinical symptoms in its early stages, but can easily progress to renal failure or even result in death. Real-time monitoring of AKI progression significantly enhances the prospects for early diagnosis and prompt intervention. However, there is no available to monitor AKI as developing a renal-clearable and reversibly responsive probe capable of long-term in vivo track biomarkers of AKI, such as reactive oxygen species (ROS), remains an extremely challenging task. Herein, we have constructed a redox-reversible second near-infrared (NIR-II) fluorescent probe based on Au nanoclusters (Au NCs) for long-term dynamic monitoring of AKI. The probe features NIR-II excitation and emission capabilities, along with effective kidney targeting and prolonged retention, facilitating renal enrichment and enabling long-term high-resolution renal imaging. Notably, it demonstrates rapid and reversible responsiveness to ROS with high sensitivity and selectivity, permitting real-time monitoring of redox fluctuations in vivo. Given its exceptional performance, the probe achieves unprecedented real-time dynamic tracking of AKI progression, providing crucial redox status information during the disease process. Additionally, the probe can serve as an effective new tool for screening of potential therapeutic drugs for AKI. This work may offer some substantial promotion for the diagnosis and treatment of kidney diseases.
危险品化学品经营许可证（带存储）