NIR-II fluorescence lymphatic imaging and intraoperative navigation based on the ?isolated cage? monodisperse strategy

Fluorescence imaging in the second near-infrared (NIR-II) window is well suited for biological systems due to lower tissue scattering and micrometer-scale resolution at depths of millimeters. Unfortunately, none of the NIR-II fluorophores have clinical application due to low quantum yields, poor photostability, and long-term biosafety concerns. Herein, we develop NIR-II fluorescent nanoprobes based on the isolated cage monodisperse strategy, which significantly inhibits the pi-pi stacking interactions and restricts internal ro-tation of the arrested indocyanine green (ICG) fluorophores, which minimizes aggregation-caused quenching and enhances their NIR-II imaging performance. Unlike ICG's imaging window of several min-utes, the nanoformulations have reduced photobleaching and provide longer observation times. The in-creased imaging time allows high spatiotemporal resolution of blood vessels and lymphatic system. Benefiting from the high resolution and sensitivity of the nanoprobes, sentinel lymph nodes are accurately removed under fluorescence navigation. More intriguingly, the patency of lymphovenous anastomosis (LVA) is presented more intuitively by qualitative and quantitative NIR-II fluorescence signals, which will directly benefit the innovation and promotion of LVA.(c) 2023 Elsevier Ltd. All rights reserved.

Automated summary

We have developed NIR-II fluorescent nanoprobes based on the isolated cage monodisperse strategy, which effectively inhibits stacking interactions and enhances the NIR-II imaging performance. Compared to ICG, the nanoformulations have reduced photobleaching and provide longer observation times, allowing high spatiotemporal resolution imaging of blood vessels and lymphatic system. The nanoprobes also enable accurate removal of sentinel lymph nodes and intuitive evaluation of lymphovenous anastomosis (LVA) through qualitative and quantitative NIR-II fluorescence signals, benefiting the innovation and promotion of LVA.