A General Strategy for Development of Activatable NIR‐II Fluorescent Probes for in vivo High‐Contrast Bioimaging

Organic-dye based NIR-II fluorescent probes, owing to their high signal-to-background ratio and deeper penetration, are highly useful for deep-tissue high-contrast imaging in vivo. However, due to the lack of suitable dyes, it is still a challenge to design activatable NIR-II fluorescent probes. In this work, we have designed a novel class of polymethine dyes (NIRII-RTs) with bright (quantum yield up to 2.03%), stable and anti-solvent quenching NIR-II emission, together with large Stokes shifts. Significantly, unlike most of reported NIR-II fluorophores which show uncontrollable fluorescence, the novel NIR-II dyes NIRII-RT3 and NIRII-RT4 equipped with the functional carboxylic-acid group could serve as effective NIR-II platforms for the design of activatable bioimaging probe with high contrast. As a proof of concept, we synthesized a series of target-activatable NIRII-RT probes (NIRII-RT-pH, NIRII-RT-ATP & NIRII-RT-Hg) for pH, adenosine triphosphate (ATP) and metal ion detecting. By applying the NIRII-RT probe, we successfully realized the real-time monitoring of drug-induced hepatotoxicity. .