Photoacoustic/Fluorescence Dual-Modality Probe for Biothiol Discrimination and Tumor Diagnosis in Cells and Mice

Developing probes to simultaneously detect and discriminate biothiols is important, yet challenging. Activatable photoacoustic (PA) probes for discriminating biothiolsin vivoarestill lacking, and this hinders the diagnosis of thiol-related diseases. Herein we present thefirst PA andfluorescence dual-modalityprobeMB-NBDfor discriminating different biothiol species. Theprobe has the advantages of bothfluorescence imaging and PAimaging (high sensitivity and deep penetration) with distinct signalpatterns toward hydrogen sulfide (H2S), cysteine/homocysteine(Cys/Hcy), and glutathione (GSH) treatment. The biothiol-activated product ofMB-NBDexhibits enhancements in near-infraredfluorescence (NIRF) at 690 nm and absorbance/PA at 664 nm upon fast reaction, allowing it to selectively detect biothiolspecies over other reactive species. On the other hand,MB-NBDdisplays characteristic absorbance enhancement at 547 nm towardH2S, rendering specific detection of H2S. In addition, the specific enhancements in absorbance/PA at 470 nm andfluorescence at550 nm toward Cys/Hcy treatment endows the probe with the capability of selectively detecting Cys/Hcy. Furthermore,MB-NBDis able to discriminate Cys and GSH byfluorescent imaging in live-cell and ratiometric PA imaging in mice experiments.MB-NBDhas been successfully used to diagnose tumors by dual-channel ratiometric PA imaging