Dang Zetao, Zheng Xue, Gao Yanli, Du Yijing, Zhang Yuewei, Zhu Shoujun
State Key Laboratory of Supramolecular Structure and Materials, Center for Supramolecular Chemical Biology, College of Chemistry, Jilin University, Changchun 130012, P.R. China.
Joint Laboratory of Opto-Functional Theranostics in Medicine and Chemistry, The First Hospital of Jilin University, Changchun 130021, P.R. China.
Sci Adv. 2025 Feb 14;11(7):eads4412. doi: 10.1126/sciadv.ads4412.
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.
内皮屏障（EB）是机体稳态机制的关键组成部分，因此开发有效的成像技术以可视化其完整性至关重要。EB破坏伴随着通透性改变甚至紧密连接（TJ）的破坏，导致白蛋白渗漏；因此，白蛋白可作为EB破坏的生物标志物。在此，我们开发了一种白蛋白特异性、共价标记的近红外II（NIR-II）染料，其对内源性白蛋白具有高选择性，用于靶向成像EB破坏。我们的白蛋白标记染料作为发色团原位构建NIR-II荧光蛋白，亮度显著提高。因此，通过将内源性白蛋白原位染料标记作为高效的“靶向剂”，我们可以精确成像各种内皮屏障的破坏。与存在酶降解或免疫系统捕获问题的传统外源性靶向剂（如染料标记抗体）不同，原位白蛋白标记在靶向成像方面表现出超高的性能。
