Renal-clearable organic NIR-II dye cluster for non-invasive ureteral imaging

Intraoperative ureter visualization is essential in colorectal cancer (CRC) surgery, but current modalities are limited by invasiveness, poor photostability, and insufficient spatial resolution. Second near-infrared (NIR-II) fluorescence imaging provides a non-invasive approach with improved tissue penetration and spatial resolution. By modulating the aggregation behavior of NIR-II dyes, intravenous administration followed by renal metabolism enables real-time, high-resolution ureteral visualization. In this study, we prepared a series of donor-acceptor-donor-based NIR-II probes through a one-pot process where dye synthesis/PEGylation and free PEG assembly occur concurrently. The IR-FEP₁₀₀₀ cluster absorbs/emits maximally at 784/1025 nm in PBS and exhibits high photobleaching resistance due to its unique structural rigidity. Importantly, the IR-FEP₁₀₀₀ cluster exhibited renal excretion and enabled superior ureteral imaging performance with excellent biocompatibility, high resolution, and a prolonged imaging window. Furthermore, the IR-FEP₁₀₀₀ cluster enabled non-invasive, effective imaging diagnosis in scenarios of accidental ureteral transection, ligation, and clamping. Moreover, the IR-FEP₁₀₀₀ cluster combined with CO-1080 and Er-NPs enables multiplexed NIR-II imaging-guided surgery. High-contrast three-channel intraoperative imaging of the CRC peritoneal metastases, the ureters, and the intestines was provided. Multiplex NIR-II imaging enables precise tumor resection while protecting vital organs from intraoperative injury. These findings highlight that the IR-FEP₁₀₀₀ cluster exhibits advantages in non-invasive, long-duration, and high-resolution ureteral imaging with broad prospects in complex surgical scenarios.