An ultra-small organic dye nanocluster for enhancing NIR-II imaging-guided surgery outcomes

The accuracy of surgery for patients with solid tumors can be greatly improved through fluorescence-guided surgery (FGS). However, existing FGS technologies have limitations due to their low penetration depth and sensitivity/selectivity, which are particularly prevalent in the relatively short imaging window (< 900 nm). A solution to these issues is near-infrared-II (NIR-II) FGS, which benefits from low autofluorescence and scattering under the long imaging window (> 900 nm). However, the inherent self-assembly of organic dyes has led to high accumulation in main organs, resulting in significant background signals and potential long-term toxicity. We rationalize the donor structure of donor–acceptor-donor-based dyes to control the self-assembly process to form an ultra-small dye nanocluster, thus facilitating renal excretion and minimizing background signals. Our dye nanocluster can not only show clear vessel imaging, tumor and tumor sentinel lymph nodes definition, but also achieve high-performance NIR-II imaging-guided surgery of tumor-positive sentinel lymph nodes. In summary, our study demonstrates that the dye nanocluster-based NIR-II FGS has substantially improved outcomes for radical lymphadenectomy.