Rational design of stable heptamethine cyanines and development of a biomarker-activatable probe for detecting acute lung/kidney injuries NIR-II fluorescence imaging.

Developing high-quality dyes to construct activatable probes for analyte sensing NIR-II fluorescence is critical for attaining enhanced imaging depths and resolution. Heptamethine cyanines can serve this purpose; however, they usually have poor stability and a tendency to self-aggregate. Herein, we present a design strategy involving the installation of pyridinium and -butyl groups onto the central cyclohexenyl core to increase steric crowding, enhance water solubility, and provide a site for the incorporation of analyte-responsive elements. The resulting NP-N dyes emit NIR-II light and can outperform benchmark heptamethine cyanines such as ICG. Using HP-N1, we developed HP-HO and showed that NIR-II fluorescence signals could be enhanced when treating with HO. HP-HO was subsequently evaluated in murine models of acute lung injury and acute kidney injury. This strategy unlocks the potential of heptamethine cyanines and is applicable to examples with extended conjugation.