Liver-Targeted Triple-Modal Molecular Probe for Visualization of Aging Marginal Donor Livers

Rapid and accurate assessment of senescence in aging marginal donor livers is critically important for liver transplantation, yet remains analytically challenging in clinical practice. Herein, we report CyC, a liver-targeted triple-modal molecular probe that integrates naked-eye colorimetric sensing with near-infrared fluorescence/photoacoustic (NIRF/PA) imaging for rapid evaluation of hepatic senescence. Upon activation by senescence-associated β-galactosidase (β-Gal), CyC produces a turn-on NIRF/PA response accompanied by a distinct blue-to-green color change visible to the naked eye. The probe exhibits high sensitivity and specificity for β-Gal, efficient liver enrichment, and strong signal contrast in senescent cells and aged mouse liver tissues. When applied to small fragments of clinical human liver samples via simple ex vivo immersion, CyC readily detects β-Gal activity. This platform integrates molecular imaging with visual sensing, offering a practical tool for rapid senescence assessment in aging marginal donor liver evaluation. By enabling immediate, instrument-free visual feedback alongside quantitative imaging, CyC has the potential to streamline intraoperative decision-making, reduce unnecessary graft discard, and ultimately expand the safe use of marginal donor livers in transplantation.