Single‐Atom C‐to‐N Editing Unlocks Bright NIR‐II J‐Aggregates for Imaging Lymphatic Metastasis

The development of near‐infrared II (NIR‐II) J‐aggregates is hindered by a lack of rational design guidelines. Here we show that single‐atom C‐to‐N skeletal editing in hemicyanine dyes precisely regulates intramolecular charge distribution and intermolecular packing, thereby allowing efficient formation of bright NIR‐II J‐aggregates. Systematic acceptor engineering reveals clear structure‐assembly‐property relationships governing J‐aggregate formation and fluorescence brightness. The optimized dye HZOE9 forms stable J‐aggregates with emission beyond 1000 nm and a quantum yield surpassing most reported cyanine‐based NIR‐II fluorophores. Mechanistic studies further elucidate that phenolic hydroxyl modification can tune J‐aggregation and NIR‐II emission, highlighting its key role in modulating supramolecular excitonic coupling. Encapsulation into biocompatible nanoparticles enables high‐resolution lymphatic imaging, real‐time metastasis visualization, fluorescence‐guided surgery, and therapeutic monitoring in vivo. This work establishes a single‐atom skeletal editing strategy for developing hemicyanine‐based NIR‐II fluorophores and provides a conceptual framework for the future development of activatable NIR‐II fluorophores via controllable supramolecular assembly.