Homo‐dyad with outer hydration layer approach for developing NIR‐II chromophore of high stability and water‐solubility as injectable and sprayable optical probe

Abstract Dyes with extended conjugate structures are the focus of extensive design and synthesis efforts, aiming to confer unique and improved optical and electronic properties. Such advancements render these dyes applicable across a wide spectrum of uses, ranging from second‐window near‐infrared (NIR‐II) bioimaging to organic photovoltaics. Nevertheless, the inherent benefits of long conjugation are often accompanied by persistent challenges like aggregation, fluorescence quenching, absorption blueshift, and low stability and poor water solubility. Herein, a unique structural design strategy termed “homo‐dyad with outer hydration layer” is introduced to address these inherent problems, tailored for the development of imaging probes exhibiting long absorption/emission wavelengths. This approach involves bringing two heptamethine cyanines together through a flexible linker, forming a homo‐dyad structure, while strategically attaching four polyethylene glycol (PEG9) chains to the terminal heterocycles. This approach imparts excellent water solubility, biocompatibility, and enhanced chemical, photo‐, and spectral stability for the dyes. Utilizing this strategy, a biomarker‐activatable probe (HD‐FL‐4PEG9‐N) for NIR‐II fluorescent and 3D multispectral optoacoustic tomography imaging is developed, and its effectiveness in disease visualization. It can not only serve as an injectable probe for acute kidney injury imaging due to its high water solubility, but also a sprayable probe for imaging bacterial‐infected wounds.