Multiplexed NIR‐II Probes for Lymph Node‐Invaded Cancer Detection and Imaging‐Guided Surgery

Abstract Tumor‐lymph node (LN) metastasis is the dominant prognostic factor for tumor staging and therapeutic decision‐making. However, concurrently visualizing metastasis and performing imaging‐guided lymph node surgery is challenging. Here, a multiplexed‐near‐infrared‐II (NIR‐II) in vivo imaging system using nonoverlapping NIR‐II probes with markedly suppressed photon scattering and zero‐autofluorescence is reported, which enables visualization of the metastatic tumor and the tumor metastatic proximal LNs resection. A bright and tumor‐seeking donor–acceptor–donor (D‐A‐D) dye, IR‐FD, is screened for primary/metastatic tumor imaging in the NIR‐IIa (1100–1300 nm) window. This optimized D‐A‐D dye exhibits greatly improved quantum yield of organic D‐A‐D fluorophores in aqueous solutions (≈6.0%) and good in vivo performance. Ultrabright PbS/CdS core/shell quantum dots (QDs) with dense polymer coating are used to visualize cancer‐invaded sentinel LNs in the NIR‐IIb (>1500 nm) window. Compared to clinically used indocyanine green, the QDs show superior brightness and photostability (no obvious bleaching even after continuous laser irradiation for 5 h); thus, only a picomolar dose is required for sentinel LNs detection. This combination of dual‐NIR‐II image‐guided surgery can be performed under bright light, adding to its convenience and appeal in clinical use.