Near‐Infrared Emissive Fluorescence Turn‐On Probe for Selective Detection of Serum Albumin Proteins in Biofluids and Living Cells

We report a novel heptamethine cyanine‐based near‐infrared (NIR) fluorescent Cy‐Cl probe that emits around 800 nm and exhibits a clear fluorescence increase upon binding to bovine serum albumin (BSA) and human serum albumin (HSA). The probe demonstrated good selectivity and sensitivity for serum albumins in different biological samples, with detection limits of 12 nM for BSA in fetal bovine serum (FBS) and 18.2 nM for HSA in real urine, along with successful detection in blood plasma. Molecular docking studies indicate that the probe selectively interacts with subdomains IB and IIIB of BSA and subdomain IIA of HSA through halogen, hydrophobic, and hydrogen bonding interactions. The probe maintains excellent fluorescence stability under physiological pH conditions. Cellular imaging data in HEK 293T, HeLa cells, and HepG2 cells confirm the high selectivity of BSA and HSA over other proteins such as fibrinogen or globulin. These findings suggested that the probe has high potential in albumin protein‐related early diagnostics, pharmacological studies, and biomedical research.