Reengineering Cyanine Dyes via Borondifluoro Indolenine: A Tunable Platform for Wash-Free Imaging and Responsive
Zixuan Zhan1, Jifa Zhang1, Tianruo Shen2
1Department of Respiratory and Critical Care Medicine, Targeted Tracer Research and Development Laboratory, Institute of Respiratory Health, Frontiers Science Center for Disease-Related Molecular Network, Precision Medicine Key Laboratory of Sichuan Province & Precision Medicine Center, State Key Laboratory of Respiratory Health and Multimorbidity, West China Hospital of Sichuan University, Chengdu, Sichuan 610041, China.
Abstract:
Fluorescent probes are essential tools for visualizing biological processes, yet conventional cyanine dyes suffer from limited structural flexibility, poor photostability, and weak compatibility with wash-free imaging. Here, we introduce a modular, neutral BF2-bridged cyanine (BCy) platform by re-engineering the indolium scaffold with a borondifluoro indolenine (BFI) fragment. BCy dyes exhibit high brightness (up to 12.4 × 104 M-1 cm-1), robust photostability, and emissions spanning 588-837 nm. The tunable BFI moiety enables the construction of wash-free, far-red/NIR probes for the plasma membrane, lipid droplets, mitochondria, and lysosomes as well as pH- and H2O2-responsive sensors. These probes support high-contrast multicolor and STED imaging, as well as dynamic organelle tracking in live cells and a mouse model of liver injury. This work establishes BF2-cyanines as robust scaffolds for next-generation fluorophores in advanced bioimaging and biomedical diagnostics.
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