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

Dyes with extended conjugate structures have been 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 NIR-II bioimaging to organic photovoltaics. Nevertheless, the inherent benefits of long conjugation are often accompanied by persistent challenges like aggregation, fluorescence quenching, absorption blue-shift and low stability and poor water solubility. Herein we introduce a unique structural design strategy termed "homo-dyad with outer hydration layer" 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, we have developed a biomarker-activatable probe (HD-FL-4PEG9-N) for NIR-II fluorescent and 3D multispectral optoacoustic tomography imaging, and demonstrated 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. This article is protected by copyright. All rights reserved.