Purification-free synthesis of bright lactoglobulin@dye nanoprobe for second near-infrared fluorescence imaging of kidney dysfunction in vivo

Kidney disease is currently prevalent worldwide but only shows insidious symptoms in the early stages. The second near-infrared window (NIR-II) fluorescence imaging has become a widely used preclinical technology for evaluating renal dysfunction due to its high resolution and sensitivity. However, bright renal clearable NIR-II fluorescence nanoprobes with a simple synthesis process are still lacking. Herein, we develop a lactoglobulin (LG)@dye nanoprobe for NIR-II fluorescence imaging of kidney dysfunction in vivo based on a purification-free method. The nanoprobe was synthesized by simply mixing LG and IR820 in aqueous solutions at 70 °C for 2 h based on the covalent interaction between the meso-Cl in IR820 and LG. The synthesized LG@IR820 nanoprobe has bright and stable NIR-II fluorescence, ultra-small size (<5 nm), low toxicity, and renal-clearable ability. The high reaction efficiency and pure aqueous reaction media make the synthesis method purification-free. In a unilateral ureteral obstruction mouse model, incipient renal dysfunction assessment was achieved by LG@IR820 nanoprobe, which couldn't be diagnosed with conventional kidney function indicators. This study provides a bright and purification-free NIR-II LG@IR820 nanoprobe to visualize kidney dysfunction at the early stage.