Developing
probes to simultaneously detect and discriminate biothiols
is important, yet challenging. Activatable photoacoustic (PA) probes
for discriminating biothiols in vivo are still lacking,
and this hinders the diagnosis of thiol-related diseases. Herein we
present the first PA and fluorescence dual-modality probe MB-NBD for discriminating different biothiol species.
The probe has the advantages of both fluorescence imaging and PA imaging
(high sensitivity and deep penetration) with distinct signal patterns
toward hydrogen sulfide (H2S), cysteine/homocysteine (Cys/Hcy),
and glutathione (GSH) treatment. The biothiol-activated product of MB-NBD exhibits enhancements in near-infrared fluorescence
(NIRF) at 690 nm and absorbance/PA at 664 nm upon fast reaction, allowing
it to selectively detect biothiol species over other reactive species.
On the other hand, MB-NBD displays characteristic
absorbance enhancement at 547 nm toward H2S, rendering
specific detection of H2S. In addition, the specific enhancements
in absorbance/PA at 470 nm and fluorescence at 550 nm toward Cys/Hcy
treatment endows the probe with the capability of selectively detecting
Cys/Hcy. Furthermore, MB-NBD is able to
discriminate Cys and GSH by fluorescent imaging in live-cell and ratiometric
PA imaging in mice experiments. MB-NBD has been successfully
used to diagnose tumors by dual-channel ratiometric PA imaging.