Dendritic NIR-II Cyanines Enable Deep Imaging and Precise Surgery

Molecular design of high-performance NIR-II fluorophores (1000-1700 nm) faces fundamental challenges, including poor aqueous stability, low quantum yield, and inadequate tumor contrast. Herein, generation-tunable poly(L-lysine) dendrimers (Cy-NIR-II-Gx) are engineered with a covalently integrated hydrophilic cyanine core (Cy-NIR-II-NH₂). The dendritic architecture suppresses H-aggregation and isolates the fluorophore from aqueous quenching, achieving a 24.3-fold quantum yield enhancement (up to 0.802% in water) and >83% photostability retention after 48-h irradiation. These advances enable deep-tissue optical penetration and high-contrast vascular/lymphatic imaging with exceptional stability, showing advantages over clinically approved indocyanine green (ICG) in specific imaging contexts. Furthermore, Cy-NIR-II-G8 exhibits superior tumor accumulation specificity to subcutaneously implanted 4T1 breast tumors via intradermal or intravenous administration, achieving sustained tumor accumulation (tumor-to-normal ratio >5 for 7 days) that meets clinical navigation standards (Rose criterion) for precision resection, with unambiguous intraoperative margin delineation validated by near-complete signal elimination post-excision. This molecular engineering strategy effectively addresses key challenges of NIR-II fluorophores and demonstrates significant clinical potential.