Finely Tuned, Meticulously Screened Renal-Clearable Zwitterionic Cyanine Dyes for Targeted NIR-II Tumor Detection, Intraoperative Navigation, and Dual-Color Imaging

Achieving clear near-infrared-II (NIR-II, 1000–1700
nm)
imaging requires dyes that selectively target tissues while clearing
rapidly from nontarget areas to reduce background noise. Based on
zwitterionic cyanine molecules, heteroatom substitutions (O, N, S)
and bridging ring modification (hexene or pentene) were employed to
fine-tune emission and brightness within the NIR-II range. The optimized
dye, ZW800-PS, demonstrated a large Stokes shift (70
nm), high brightness (692 M–1 cm–1), rapid renal clearance, and excellent biocompatibility. Conjugation
with αvβ3 integrin-targeting ligands
enabled superior tumor imaging in 4T1, U87, and A549 tumor-bearing
mouse models, achieving tumor-to-muscle ratios of over 5. Additionally,
conjugation with prostate-specific membrane antigen ligands allowed
precise prostate cancer diagnostics. The dye demonstrated exceptional
potential for intraoperative navigation, allowing for precision tumor
margins distinguishment and tiny residual tumorous tissues detection.
Integrating with an NIR-II excitable probe enabled real-time, multitarget
imaging for precise tumor resection and tissue preservation during
surgery.