Quantitative Near-Infrared Photoacoustic Imaging of Gamma-Glutamyl Transpeptidase Activity in Tumors

Gamma-glutamyl transpeptidase (GGT) is essential for glutathione metabolism and is overexpressed in many cancers, making its sensitive and quantitative detection crucial for early cancer diagnosis. However, existing imaging strategies often lack sufficient sensitivity and accuracy. Herein, we present a near-infrared (NIR), ratiometric photoacoustic nanoprobe (Au NR@PEG@IR775-PEI@PBEAGA) for quantitative GGT detection. This nanoprobe is fabricated by sequential coating Au nanorod (Au NR) with polyethylene glycol (PEG), IR775-doped polyethylenimine (PEI), and GGT-responsive polymer, poly-2-(L-γ-glutamyl-L-α-aminobutyrylamino)ethyl acrylamide (PBEAGA). It has dual photoacoustic signals at 775 and 930 nm; upon GGT cleavage, IR775 is released, reducing the 775 nm signal while the 930 nm signal remains an internal reference. The ratiometric readout (PA₇₇₅/PA₉₃₀) enables robust GGT quantification with a limit of detection of 0.48 U/mL. In vivo studies showed the real-time tumor imaging and noninvasive assessment of GGT activity. We envision this nanoprobe will be used to diagnose early cancers in the clinic in the future.