Ultrabright Renal-Clearable Cyanine-Protein Nanoprobes for High-Quality NIR-II Angiography and Lymphography
Jiajun Xu, Tianyang Han, Yajun Wang, Feiran Zhang, Mengfei Li, Lang Bai, Xinyu Wang, Bin Sun, Xin Wang, Jianshi Du, Kun Liu, Junhu Zhang, Shoujun Zhu
Abstract
The renal-clearable aspect of imaging agent with minimum toxicity issues and side effects is essential for clinical translation, yet clinical near-infrared-I/II (NIR-I/II) fluorophores with timely renal-clearance pathways are very limited. Herein, we rationally develop the cyanine-protein composite strategy through covalent bonding of β-lactoglobulin (β-LG) and chloride-cyanine dye to produce a brilliant and stable NIR-I/II fluorophore (e.g., β-LG@IR-780). The β-LG acts as a protecting shell with small molecular weight (18.4 kDa) and ultrasmall size (<5 nm), thus endowing the β-LG@IR-780 with excellent biocompatibility and renal excretion. Our β-LG@IR-780 probe enables noninvasive and precise NIR-II visualization of the physiological and pathological conditions of the vascular and lymphatic drainage system, facilitating intraoperative imaging-guided surgery and postoperative noninvasive monitoring. The minimum accumulation of our probes in the main organs improves the overall biosafety. This study provides a facile methodology for new-generation NIR-II fluorophores and largely improves the brightness and pharmacokinetics of small molecular dyes.