In situ albumin tagging for targeted imaging of endothelial barrier disruption

The endothelial barrier (EB) is a critical component of the body's homeostatic mechanisms, thus developing effective imaging techniques to visualize its integrity is essential. The EB disruption is accompanied by the alternations in permeability and even the breakdown of tight junctions (TJs), leading to the leakage of albumin; thus, albumin can serve as a biomarker for EB disruption. Herein, we develop an albumin-specific, covalently tagged near-infrared II (NIR-II) dye, with its high selectivity for endogenous albumin, for targeted imaging EB disruption. Our albumin-tagging dye serves as a chromophore to construct NIR-II fluorescent proteins in situ, with substantially improved brightness. Thus, through in situ dye tagging of endogenous albumin as the efficient "targeting agent," we can precisely image disruptions in various endothelial barriers. Unlike the traditional exogenous targeting agents (e.g., dye-labeled antibodies) with enzymatic degradation or immune system capture issues, in situ albumin tagging demonstrates superhigh performance for targeted imaging.