Dendritic NIR‐II Cyanines Enable Deep Imaging and Precise Surgery

Abstract 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‐NH 2 ). 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.