Super-stable cyanine@albumin fluorophore for enhanced NIR-II bioimaging
Lang Bai, Zhubin Hu, Tianyang Han, Yajun Wang, Jiajun Xu, Guanyu Jiang, Xin Feng, Bin Sun, Xiangping Liu, Rui Tian, Haitao Sun, Songling Zhang, Xiaoyuan Chen, Shoujun Zhu
Abstract
Near-infrared-II (NIR-II) dyes could be encapsulated by either exogenous or endogenous albumin to form stable complexes for deep tissue bioimaging. However, we still lack a complete understanding of the interaction mechanism of the dye@albumin complex. Studying this principle is essential to guide efficient dye synthesis and develop NIR-II probes with improved brightness, photostability, etc. Methods: Here, we screen and test the optical and chemical properties of dye@albumin fluorophores, and systematically investigate the binding sites and the relationship between dye structures and binding degree. Super-stable cyanine dye@albumin fluorophores are rationally obtained, and we also evaluate their pharmacokinetics and long-lasting NIR-II imaging abilities. Results: We identify several key parameters of cyanine dyes governing the supramolecular/covalent binding to albumin, including a six-membered ring with chlorine (Cl), the small size of side groups, and relatively high hydrophobicity. The tailored fluorophore (IR-780@albumin) exhibits much-improved photostability, serving as a long-lasting imaging probe for NIR-II bioimaging.