Mechanochemical Acceptor Engineering for NIR-I and NIR-II Fluorophores Enabling Orthogonal Ureter-Vascular Image-Guided Surgery

Accurate intraoperative identification of the ureters and surrounding vasculature is essential for preventing iatrogenic injuries during laparoscopic surgery. While fluorescence imaging (FLI) offers a promising solution, conventional single-channel systems lack the capacity for multistructure anatomical differentiation. Here, we present a dual-channel near-infrared (NIR) FLI strategy facilitated by mechanochemistry-assisted acceptor engineering, which allows the subsequent screening of spectrally orthogonal fluorophores. Two of the resulting NIR fluorophores, TQx-FTA (NIR-I, λ em = 755 nm) and TPzCl-FTA (NIR-II, λ em = 1122 nm), exhibit large Stokes shifts of up to 280 nm, minimal spectral overlap, and high photostability. When formulated into nanoparticles, they enable high signal-to-background ratios and crosstalk-free imaging under white-light and 980 nm excitation. In rabbit models, both antegrade and retrograde infusion workflows provided high-contrast visualization of the ureters and vasculature. The system accurately detected ureteral pathologies, including strictures, obstructions, and injury-induced leakage, with quantitative fluorescence profiles confirming the anatomical precision. Compared to single-channel imaging, the dual-channel system offered a superior ability for structural differentiation. This integrated chemical and imaging platform overcomes key limitations in conventional FLI and offers a clinically translatable approach for high-resolution surgical navigation.