An activatable near-infrared molecular reporter for fluoro-photoacoustic imaging of liver fibrosis.

Noninvasive and accurate detection of liver fibrosis is extremely significant for well-timed intervention and treatment to prevent or reverse its progression. Fluorescence imaging probes hold great potential for imaging of liver fibrosis, but they always encounter the inherent limitation of shallow penetration depth, which compromises their ability of in vivo detection. To overcome this issue, an activatable fluoro-photoacoustic bimodal imaging probe (IP) is herein developed for specific visualization of liver fibrosis. The probe IP is constructed on a near-infrared thioxanthene-hemicyanine dye that is caged with gamma-glutamyl transpeptidase (GGT) responsive substrate and linked with integrin-targeted peptide (cRGD). Such molecular design permits IP to effectively accumulate in the liver fibrosis region through specific recognition of cRGD towards integrin and activate its fluoro-photoacoustic signal after interaction with overexpressed GGT to precisely monitor the liver fibrosis. Thus, our study presents a potential strategy to design dual-target fluoro-photoacoustic imaging probes for noninvasive detection of early-stage liver fibrosis.