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.

Ultrafast photochemistry produces superbright short-wave infrared dots for low-dose in vivo imaging

“…In this spectral range, the absorption and scattering coefficients of biological tissues are reduced to a minimum, allowing high-contrast, high-resolution in vivo imaging at large (>1 cm) tissue depths 9 . NIR-II fluorescent materials have changed the game in preclinical imaging 10,11 , enabling high-resolution anatomical imaging 12,13 , tumor detection 14,15 , biosensing 16 , brain vasculature mapping 17,18 , image-guided genome editing 19 and surgery 20,21 , and dynamic tracking of metabolic processes 22 . NIR-II-emitting Ag 2 S nanocrystals do not contain highly toxic heavy metal ions, unlike other nanoprobes operating in this spectral range, minimizing biocompatibility concerns and making them one of the most promising systems among all currently reported NIR-II fluorophores 23,24 .…”

Near-infrared-IIb probe affords ultrahigh contrast inflammation imaging

“…NIR-IIb probes with extremely low tissue scattering and auto-uorescence have afforded ultrahigh imaging contrast and penetration depth. [45][46][47]49 We initially tested the optimal surface modication and identied a two-layer-surface coating that improved biosafety of QDs (the dynamic light scattering (DLS) size of QDs is about 35 nm and the zeta potential of the QDs is about À1.4 eV). The coated QDs possessed superbright NIR-IIb emission with peak emission at 1600 nm.…”

“…The coated QDs possessed superbright NIR-IIb emission with peak emission at 1600 nm. [45][46][47] The QDs also exhibited outstanding photostability during the exposure to a high-power 808 nm laser, eliminating quantication problems that could be caused by signal decay. The large Stokes shi, widely recognized to be critical for background signal reduction, improved imaging quality (Fig.…”

“…44 Thus, NIR-IIb imaging has been used to achieve high resolution of mouse vasculature, tumors, lymph nodes and visualize immune therapy process. 41,42,[45][46][47][48] More importantly, broadening the NIR window from 700 to over 1500 nm may potentially integrate multiple channels for imaging complex biological events.…”

“…The NIR-IIb quantum dot (QD) probe with the core-shell structure was synthesized by using a protocol similar to that described in our previous work. [45][46][47] The amphiphilic polymer oleylamine-poly(acrylic acid) (OPA) was used to deliver the oil-soluble QDs to a water-soluble phase and a combination of m-polyethyleneglycol (PEG)-amine and 8-arm PEG-amine was used to improve the biocompatibility and in vivo circulation time of the QD probe. The as-prepared QDs enabled high-quality vessel imaging, whereas the prolonged circulation also improved probe accumulation in the sites of inammation.…”