Combination of changeable π-conjugation and hydrophilic groups for developing water-soluble small-molecule NIR-II fluorogenic probes

Abstract

Small-molecule probes emitting in the second near-infrared window (NIR-II) are attracting great attention because of their deep-tissue imaging ability. However, developing NIR-II fluorogenic (off–on) probes with good water solubility remains a great challenge due to the lack of a facile approach. Herein we first report the combination of changeable π-conjugation and hydrophilic groups as an effective strategy for developing water-soluble NIR-II fluorogenic probes. With the strategy, new water-soluble NIR-II fluorophores are prepared, among which NIR-II-F2 and NIR-II-F3 show superior stability and bright fluorescence in aqueous media, and are thus used to design two water-soluble NIR-II fluorogenic probes for leucine aminopeptidase (LAP). The excellent performance in real aqueous bio-environments is demonstrated by imaging mouse vasculatures and organs with NIR-II-F2, and LAP in drug-induced liver injury mice with one of the enzymatic probes; however, water-insoluble dyes cannot achieve such in vivo imaging under the same conditions. Our strategy may be helpful for further developing water-soluble organic NIR-II fluorogenic probes for in vivo imaging of other analytes.