H-Aggregated Squaraine Probe NIR-II/MRI Double Reversal Imaging for Liver Cancer Precise Surgical Navigation.

Accurate delineation of tumor boundaries is critical for the complete resection of early-stage liver cancer but remains a challenge for single-modality imaging. Here, we present SQ 905-Gd, a small-molecule squaraine-based dual-modality probe designed for NIR-II and MRI imaging to address this need. This probe uniquely leverages an aggregation-caused quenching (ACQ) effect and intrinsic liver-targeting properties to enable a double-reversal imaging strategy. Preoperatively, SQ 905-Gd enhances T-weighted MRI, brightening liver tumors. Intraoperatively, the same aggregates quench NIR-II fluorescence, darkening tumors against normal tissue and allowing clear visualization of sub‑2 mm lesions. Additionally, fluorescence can be restored ex vivo by solvent extraction, enabling real-time confirmation of complete resection. To our knowledge, this is the first small-molecule dual-modal probe that utilizes in vivo ACQ to achieve bright/dark reversible contrast across both MRI and NIR-II imaging, offering a powerful tool for precise liver cancer surgery.